Prebiotic combinations

Abstract

The technology described herein is directed to compositions comprising an amount of maltitol effective to increase or decrease the relative and / or absolute abundance of at least one bacterium in the gut of a mammal. The compositions can be prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions. Also described herein are methods of using such compositions, such as to improve mood, promote relaxation, promote a calming mood state, reduce stress or anxiety, increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one bacterial species, and / or to increase the production rate and / or concentration of γ-aminobutyric acid (GABA). Also described herein are methods of treating depression, anxiety, stress, and / or other mental health disorders.

Description

PREBIOTIC COMBINATIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit under 35 U.S.C. § 119(c) of U.S. Provisional Application No. 63 / 558,361 filed February 27, 2024, the contents of which are incorporated herein by reference in their entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted in XML format via Patent Center and is hereby incorporated by reference in its entirety. Said XML copy, created on February 19, 2025, is named 083103_000100WOPT.xml and is 1,293,477 bytes in size.TECHNICAL FIELD

[0003] The technology described herein relates to prebiotic combmations.BACKGROUND

[0004] The human gut microbiome is an essential component of host physiology that strongly influences health and disease. Recent evidence demonstrates that disruptions of the gut microbiota's composition and activity can influence the onset and progression of various disorders, including those considered neuropsychiatric in origin, such as anxiety (Borrego-Ruiz et al., 2023; Cenit et al., 2017; Ge et al., 2021; Shoubridge et al.. 2022). This connection between gut microbiome disruptions and neuropsychiatric symptoms underscores the significance of the microbiome-gut-brain axis.

[0005] The gut-brain axis is a bidirectional network that links the enteric nervous system (ENS) of the gut to the central nervous system (CNS). It involves complex neural, endocrine, immune, and humoral pathways, all of which are notably impacted by the gut microbiome (Cryan et al.. 2019). Although the full extent of the gut microbiome's impact on the gut-brain axis remains to be fully elucidated, evidence suggests that metabolites produced by gut bacteria play a fundamental role in this connection, as microbial metabolites have been shown to impact both physiological and psychological processes (Cryan et al.. 2019; Mayer, Tillisch, & Gupta, 2015). This is unsurprising, as a large proportion of blood metabolites are believed to be produced or altered by the gut microbiome (Wikoff et al., 2009). Additionally, the immune system plays a critical role in this comrection, with the gut microbiome modulating immune responses in ways that impact the ENS and CNS (Cryan et al., 2019). For example, germ-free mice who lack a microbiome have been shown to have severe defects in microglia function (Erny et al., 2015), demonstrating the importance of the microbiome on the immuno-landscape of the CNS. Furthermore, the vagus nene serves as a direct neural link between gut microbes and the brain and is likely pivotal to the microbiome -gut-brain axis (Bonaz, Bazin, &Pcllissicr, 2018). For instance, the bacterial product lipopolysaccharide is a known activator (via TLR4 receptors) of vagal afferent fibers, whose activation leads to a response cascade directly impacting neural and immune responses (Hosoi et al., 2005). Given the influence of the microbiome on the gut-brain axis and neurological health, the microbiome can be leveraged for the prevention and treatment of neuropsychiatric disorders and symptoms.

[0006] y-Aminobutyric acid (GABA) is the primary inhibitory nemotransmitter in the mammalian central nervous system and plays a crucial role in regulating neuronal excitability. Activation of GABA receptors results in the hyperpolarization of neurons, reducing the likelihood of a neuronal action potential (Ngo and Vo, 2019). Thus, increased GABA is generally associated with a reduction in anxiety and mood disorders (Lydiard, 2003). Some bacteria in the gut microbiome produce GABA at potentially physiologically relevant levels; in particular, the genus Bacteroides. a dominant taxon in the healthy human microbiome, is a major producer of GABA in the human gut (Strandwitz et al., 2019). Notably, a depletion in Bacteroides in the gut microbiome is associated with neuropsychiatric disorders and low mood symptoms (Strandwitz et al., 2019). Microbiome-produced GABA likely influences the gut-brain axis and CNS activity via the hypothalamic-pituitary -adrenal axis, the vagus nerve, and other mechanisms. Restoring or increasing GABA production in the microbiome by increasing the abundance of Bacteroides is a promising strategy for the prevention and treatment of neuropsychiatric disorders and symptoms associated with low GABA levels. Gut microbiome-derived GABA can move to other tissues, fluids, organs, or locations in the subject, such as in the feces or blood. As such, a low GABA level or a low GABA concentration can be detected in samples from at least the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a subject.

[0007] Beyond the depletion of Bacteroides in neuropsychiatric disorders, microbiome composition shifts have been observed in a plethora of indications (Hou et al., 2022). Elevated levels of the proinflammatoiy family of bacteria Enterobacteriaceae have been associated with a wide range of diseases, including inflammatory bowel disease (Ni et al., 2017), colorectal cancer (Allen-Vercoe and Jobin. 2014), atherosclerotic cardiovascular disease (Jie et al., 2017), and schizophrenia (Zhuang et al., 2020). Enterobacteriaceae exacerbate inflammation, creating a complex cycle of inflammation and contributing further to disease (Zeng et al., 2017). Reducing or inhibiting Enterobacteriaceae growth in the gut microbiome can serve as a strong prophylactic or therapeutic approach for myriad diseases.

[0008] Diet interventions that can modulate the gut microbiome and thus the gut-brain axis are greatly needed.SUMMARY|0009| The technology described herein is directed to compositions comprising an amount of maltitol effective to increase or decrease the relative and / or absolute abundance of at least one bacterium. The compositions can be prebiotic compositions, synbiotic compositions, nutritional supplements, foodcompositions, medical foods, and / or pharmaceutical compositions. Also described herein are methods of using such compositions, such as to improve mood, promote relaxation, promote a calming mood state, reduce stress or anxiety, increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one bacterial species, and / or to increase the production rate and / or concentration of y-aminobutyric acid (GABA). Also described herein are methods of treating depression, anxiety, stress, and / or other mental health disorders.

[0010] Accordingly, in one aspect, described herein is a prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bacteroides in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase the relative and / or absolute abundance of the at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control.

[0011] In one aspect, described herein is a prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase relative abundance of the at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control. In one embodiment of this or any other aspect described herein, a prebiotic composition that promotes growth or metabolite production by beneficial bacteria, including, but not limited to beneficial Bacteroides and / or Bifidobacteria species, does not promote growth of Enterobacteriaceae species.

[0012] In one aspect, described herein is a prebiotic composition for decreasing the relative and / or absolute abundance of at least one bacterium of the family Enterobacteriaceae in the gut of a mammalian subject, the prebiotic composition comprising an amount of maltitol effective to decrease the relative and / or absolute abundance of the at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject compared to other formulations containing a sweetener that is not maltitol.

[0013] In some embodiments of any of the aspects, the effective amount of maltitol is comprised by a unit amount of the prebiotic composition.

[0014] In some embodiments of any of tire aspects, the effective amount of maltitol is a concentration of at least 1% to at most 100% w / w maltitol.

[0015] In some embodiments of any of die aspects, the effective amount of maltitol is 0.5g to 25g per unit or serving.

[0016] In some embodiments of any of die aspects, the form of maltitol is selected from the group consisting of maltitol syrup, maltitol powder, maltitol crystals, and maltitol gel.

[0017] In some embodiments of any of the aspects, the maltitol syrup comprises about 5% sorbitol.

[0018] In some embodiments of any of the aspects, at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium internalizes, is supported by, and / or metabolizes the effective amount of maltitol in the composition in the gut of the mammalian subject.

[0019] In some embodiments of any of the aspects, the mammalian subject is a human.

[0020] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject.

[0021] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-internalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject.

[0022] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.

[0023] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject.

[0024] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.

[0025] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacteroides or the at least one bacterium of the genus Bifidobacterium in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder.

[0026] In some embodiments of any of the aspects, the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

[0027] In some embodiments of any of the aspects, treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder.

[0028] In some embodiments of any of the aspects, at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

[0029] In some embodiments of any of the aspects, the prebiotic composition further comprises at least one excipient selected from the group consisting of encapsulation materials (e.g.. chitosan, wax, and gelatin), solubilizers (e.g., TWEEN 80 or SPAN 60), bulking agents (e.g., maltodextrin or microcrystalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g., ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof.

[0030] In some embodiments of any of the aspects, the prebiotic composition further comprises at least one additional prebiotic selected from the group consisting of amino acid (e.g., arginine, glutarate, and ornithine), biotin, fructooligosaccharide, galactooligosaccharide, hemi cellulose (e.g.. arabinoxylan, xylan, xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide,oligofructosc-cnrichcd inulin, gum (c.g., guar gum, gum arabic, and carrageenan), oligofructosc, oligodextrose, tagatose, resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide, pectin (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fiber (e.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccharidc. and polyamine (e.g., spermidine, putrescine).

[0031] In some embodiments of any of the aspects, the prebiotic composition is fonnulated for delivery to the gut of a mammalian subject.

[0032] In some embodiments of any of the aspects, the prebiotic composition is in the form of a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a candy, a syrup, an elixir, a lozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.|0033| In some embodiments of any of the aspects, wherein the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence selected from Table 7.

[0034] In some embodiments of any of the aspects, the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence comprising one of SEQ ID NOs: 46-89 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 46-89.

[0035] In some embodiments of any of the aspects, the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8.

[0036] In some embodiments of any of the aspects, the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 8.

[0037] In some embodiments of any of the aspects, the prebiotic increases the relative and / or absolute abundance of at least one bacterium selected from the “increased” column of Table 11.

[0038] In some embodiments of any of the aspects, the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence selected from Table 12.

[0039] In some embodiments of any of the aspects, tire prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence comprising one of SEQ ID NOs: 207-360 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 207- 360.

[0040] In some embodiments of any of the aspects, the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 13.

[0041] In some embodiments of any of the aspects, the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 13 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 13.

[0042] In some embodiments of any of the aspects, the prebiotic increases the relative and / or absolute abundance of a combination of bacteria selected from Table 16.

[0043] In some embodiments of any of the aspects, the prcbiotic decreases the relative and / or absolute abundance of at least one bacterium selected from the “decreased” column of Table 11.

[0044] In some embodiments of any of the aspects, the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence selected from Table 14.

[0045] In some embodiments of any of the aspects, the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence comprising one of SEQ ID NOs: 361-596 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 361 - 596.

[0046] In some embodiments of any of the aspects, the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 15.|0047| In some embodiments of any of the aspects, the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 15 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 15.

[0048] In one aspect, described herein is a synbiotic composition comprising a prebiotic composition as described herein and at least one bacterial species.

[0049] In one aspect, described herein is a synbiotic composition comprising maltitol and at least one bacterial species.

[0050] In some embodiments of any of tire aspects, the synbiotic composition comprises an amount of maltitol effective to increase the growth rate and / or metabolic activity of at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when tire prebiotic composition is consumed by the mammalian subject.

[0051] In some embodiments of any of tire aspects, the sy nbiotic composition comprises an amount of maltitol effective to increase the growth rate and / or metabolic activity of at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when tire prebiotic composition is consumed by the mammalian subject.

[0052] In some embodiments of any of the aspects, the synbiotic composition comprises an amount of maltitol effective to decrease the growth rate and / or metabolic activity of at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject.

[0053] In some embodiments of any of the aspects, the effective amount of maltitol is comprised by a unit amount of the synbiotic composition.

[0054] In some embodiments of any of the aspects, the effective amount of maltitol is a concentration of at least 1% to at most 100% w / w maltitol.

[0055] In some embodiments of any of the aspects, die at least one bacterial species is at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species encodes and / or expresses a protein or protein complex that internalizes and / or metabolizes maltitol.

[0056] In some embodiments of any of the aspects, the protein or protein complex that internalizes and / or metabolizes maltitol is selected from Table 9 or Table 10.

[0057] In some embodiments of any of the aspects, the protein or protein complex that internalizes and / or metabolizes maltitol is maltitol dehydrogenase or a-glucosidase.

[0058] In some embodiments of any of the aspects, the protein or protein complex that internalizes maltitol comprises one of SEQ ID NOs: 171-206 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 171-206 that maintains its function as a polypeptide.|0059| In some embodiments of any of the aspects, the protein or protein complex that metabolizes maltitol comprises one of SEQ ID NOs: 90-170 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 90-170 that maintains its function as a polypeptide.

[0060] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence selected from Table 5 or Table 12.

[0061] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or 207-360 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 1-45 or 207-360.

[0062] In some embodiments of any of tire aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 6 or Table 13.

[0063] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 6 or Table 13 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 6 or Table 13.

[0064] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a combination of bacteria selected from Table 16.

[0065] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is dried and / or viable.

[0066] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is freeze-dried and / or spray -dried.

[0067] In some embodiments of any of die aspects, the at least one maltitol-intcmalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is a viable, isolated bacterial species.

[0068] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is present at a concentration of at a concentration of at least 101colony forming units per gram (CFU / g) to at most 1013CFU / g.

[0069] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is at least one bacterium of the genus Bacteroides.

[0070] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifaciens, B. caccae, B. caecicola. B. caecigallinarum, B. cellulosilyticus, B. cellulosolvens. B. clarus, B. coagulans, B. coprocola, B. coprophilus, B. coprosuis, B. dorei, B. eggerthii, B. faecichinchillae, B. faecis, B. finegoldii, B. fluxus, B. fragilis, B. galacturonicus, B. gallinaceum, B. gallinarum, B. goldsteinii, B. graminisolvens. B. helcogene. B. intestinalis. B. luti, B. massiliensis. B. nordii. B. oleiciplemts, B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifaciens, B. putredinis, B. pyogenes, B. reticulotermitis, B. rodentium, B. salanitronis, B. salyersiae, B. sartorii. B. stercoris. B. thetaiotaomicron, B. uniformis, B. vulgatus, and B. xylani solvens.

[0071] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 1-45.

[0072] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides comprises a genome selected from Table 6 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 6.

[0073] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides encodes and expresses a protein or protein complex that internalizes and / or metabolizes maltitol.

[0074] In some embodiments of any of the aspects, the protein or protein complex that internalizes and / or metabolizes maltitol comprises one of SEQ ID NOs: 179-295 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 179-295 that maintains its function as a polypeptide.

[0075] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides internalizes and / or metabolizes the maltitol in the composition in the gut of a mammalian subject.|0076| In some embodiments of any of the aspects, the mammalian subject is a human.

[0077] In some embodiments of any of the aspects, the internalization and / or metabolization by or die support of die at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides by at least 1% in the gut of the mammalian subject.

[0078] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing. and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides by at least 1% in the gut of the mammalian subject.

[0079] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the concentration of y-aininobutyric acid (GABA) by at least 1% in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.

[0080] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aininobutyric acid (GABA) in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject.

[0081] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aininobutyric acid (GABA) in the gut, blood plasma or scrum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.

[0082] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aininobut ric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacteroides in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder.

[0083] In some embodiments of any of the aspects, the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR-MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's. Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

[0084] In some embodiments of any of the aspects, treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder.

[0085] In some embodiments of any of the aspects, at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

[0086] In some embodiments of any of the aspects, the synbiotic composition further comprises at least one excipient selected from the group consisting of encapsulation materials (e.g., chitosan, wax, and gelatin), solubilizers (e.g., Tween 80 or Span 60), bulking agents (e.g., maltodextrin or microcrystalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g., ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof.

[0087] In some embodiments of any of the aspects, the synbiotic composition further comprises at least one additional prebiotic selected from the group consisting of amino acid (e.g., arginine, glutarate, and ornithine), biotin, fructooligosaccharide, galactooligosaccharide, hemi cellulose (e.g., arabinoxylan, xylan, xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, gum (e.g., guar gum, gum arabic, and carrageenan), oligofructose, oligodextrose, tagatosc, resistant maltodcxtrins (e.g., resistant starch), trans-galactooligosaccharidc, pectin (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fiber (e.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccharidc. and polyamine (e.g., spermidine, putrescine).

[0088] In some embodiments of any of the aspects, the synbiotic composition is formulated for delivery to the gut of a mammalian subject.

[0089] In some embodiments of any of the aspects, the synbiotic composition is in the form of a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

[0090] In one aspect, described herein is a nutritional supplement comprising a prebiotic composition as described herein or a synbiotic composition as described herein.

[0091] In some embodiments of any of the aspects, the prcbiotic composition or the synbiotic composition is at a concentration of at least 1% to at most 70% in the nutritional supplement.

[0092] In some embodiments of any of the aspects, the nutritional supplement is formulated for delivery to the gut of a mammalian subject.

[0093] In some embodiments of any of the aspects, the nutritional supplement is in the form of a probiotic, a prebiotic, a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

[0094] In one aspect, described herein is a food composition comprising a prebiotic composition as described herein or a synbiotic composition as described herein.|0095| In some embodiments of any of the aspects, the food composition is selected from the group consisting of milk, yogurt, plant-based daily' alternatives (e.g., oat milk, almond milk, coconut milk, soy milk, pea milk, etc.), soft drinks (e.g., soda, carbonated water, etc.) fermented milk, protein shakes, fruit juice (e.g.. apple juice, orange juice, grapefruit juice, grape juice, etc.), non-dairy fermented beverages (e.g., kombucha. etc.), vegetable juices (e.g. carrot juice, tomato juice, etc.), alcoholic beverages (e.g.. canned cocktail, alcoholic cider, etc ), sauces (e.g., gravy, tomato sauce, barbeque sauce, etc ), broth and stock (e.g., chicken stock, beef broth, vegetable broth, etc.), syrups, tea beverages (e.g.. tea-based powder, milk tea, etc ), coffee beverages (e.g.. cold brew, latte, iced coffee), yogurt beverages, or cereal-based beverages (e.g., rice milk, beer, barley tea, etc.).

[0096] In some embodiments of any of the aspects, the food composition is selected from the group consisting of granola bars, meal replacement bars, protein bars, fruit bars, breakfast cereals, pastas, bread products (e.g., loaves, buns, croutons, etc.), condiments and relishes (e.g., ketchup, relish, etc.), frosting, gelatin and pudding, cough drops, or jams and jellies.

[0097] In some embodiments of any of the aspects, the food composition is selected from the group of food concentrates consisting of bouillon concentrate, soup concentrate, or gravy concentrate.

[0098] In some embodiments of any of the aspects, the food composition is a confectionary selected from the group consisting of a chocolate composition, a chocolate analogue composition, chewing gum, soft chew candy, gummy candy, or hard candy.

[0099] In some embodiments of any of the aspects, the food composition is a frozen confection (e.g., ice cream, sorbet, sherbet, frozen yogurt or water ice), is a frozen confection product comprising a frozen composition and a chocolate composition or a chocolate analogue composition wherein the chocolate composition or a chocolate analogue composition is in the form of a coating on the frozen composition and / or inclusions located within the frozen composition and / or a ripple or swirl of sauce.

[0100] In some embodiments of any of the aspects, the prebiotic composition or the synbiotic composition is at a concentration of at least 1% to at most 70% in the food composition.

[0101] In one aspect, described herein is a medical food for the improvement of mood, the promotion of relaxation, the promotion of a calming mood state, and / or the treatment of depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, comprising an effective amount of maltitol, wherein the medical food is formulated to provide a daily dosage of maltitol in the effective amount of 0.5g to 25g based on a serving size of about 0.8g to 125g of said medical food taken up to three times a day.

[0102] In one aspect, described herein is a medical food for the improvement of mood, the promotion of relaxation, the promotion of a calming mood state, and / or the treatment of depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, comprising an effective amount of maltitol and at least one bacterial species, wherein the medical food is formulated to provide (a) a daily dosage of maltitol in the effective amount of 0.5g to 25g and (b) a daily dosage of the at least one bacterial species of 101CFU / g to 1013CFU / g, based on a serving size of about 0.8g to 125 g of said medical food taken up to three times a day.

[0103] In one aspect, described herein is a use of maltitol in a food composition as described herein or in a medical food as described herein, for replacing sugar in the food composition or in the medical food.

[0104] In one aspect, described herein is a pharmaceutical composition comprising a prebiotic composition as described herein or a synbiotic composition as described herein, and a pharmaceutically acceptable carrier.

[0105] In some embodiments of any of the aspects, the prebiotic composition or the synbiotic composition is at a concentration of at least 1% to at most 70% in the pharmaceutical composition.

[0106] In some embodiments of any of the aspects, the pharmaceutical composition is formulated for delivery to the gut of a mammalian subject.

[0107] In some embodiments of any of the aspects, the pharmaceutical composition is in the form of a probiotic, a prebiotic, a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

[0108] In one aspect, described herein is a use of maltitol in die preparation of a medicament for the treatment of a disease or disorder related to low or reduced GABA levels.

[0109] In some embodiments of any of the aspects, the disease or disorder related to low or reduced GABA levels is a mental disease or disorder.

[0110] In some embodiments of any of the aspects, the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression.catatonic depression, postpartum depression, and seasonal affective disorder), ncurodc generative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

[0111] In one aspect, described herein is a method of improving mood in a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.|00112] In one aspect, described herein is a method of promoting relaxation and / or promoting a calming mood state in a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0113] In one aspect, described herein is a method of reducing stress or anxiety in a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0114] In one aspect, described herein is a method of increasing the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0115] In one aspect, described herein is a method of increasing the production rate of y- aminobutyric acid (GABA) by at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides in the gut of a mammalian subject or at least one bacterium of the genus Bifidobacterium, and / or increasing the concentration of y-a inobul ric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, anutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0116] In one aspect, described herein is a method of treating depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, the method comprising administering an effective amount of a prebiotic composition as described herein, a symbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmacal composition as described herein.

[0117] In some embodiments of any of the aspects, the mammalian subject is a human.

[0118] In some embodiments of any of the aspects, the administering is to the gut of the subject.

[0119] In some embodiments of any of the aspects, improving mood in the mammalian subject, promoting relaxation and / or promoting a calming mood state in the mammalian subject, and / or reducing stress and / or anxiety in the mammalian subject is measured by a test selected from the group consisting of the Hopkins Symptom Checklist-25, Hamilton Depression Rating Scale, the Beck Depression Inventory, Positive and Negative Affect Schedule, Profile of Mood states (POMS) Questionnaire, a friendliness score, General Anxiety Disorder Questionnaire-7 (GAD-7). Visual Analog Mood Scale, VAS / Likert Scale, Perceived Stress Scale. Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9. Center for Epidemiologic Studies Depression Scale, Geriatric Depression Scale, Montgomery -Asberg Depression Rating Scale. Cohen’s Perceived Stress Scale, Holmes and Rahe Stress Scale, World Health Organization Quality of Life, Short Form Health Survey (SF-36), and EuroQol five dimensions questionnaire, or a combination thereof.

[0120] In some embodiments of any of the aspects, mood is improved in the subject by at least 5%.

[0121] In some embodiments of any of the aspects, relaxation is promoted in the subject by at least 5%.

[0122] In some embodiments of any of the aspects, a calming mood state is promoted in tire subject by at least 5%.

[0123] In some embodiments of any of the aspects, stress and / or anxiety is reduced in the subject by at least 5%.

[0124] In some embodiments of any of the aspects, at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium internalizes and / or metabolizes and / or is supported by maltitol from the composition in the gut of the mammalian subject.

[0125] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relativeand / or absolute abundance of the at least one maltitol-intemalizing, and / or maltitol-mctabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject.

[0126] In some embodiments of any of the aspects, the increase of the relative and / or absolute abundance of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium is determined by: (i) quantifying the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject before ingestion of the composition; (ii) quantifying the at least one maltitol-intemalizing. and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject after ingestion of the composition; (iii) and determining the relative and / or absolute abundance of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium from the data from (ii) compared to the data from (i).

[0127] In some embodiments of any of the aspects, quantification of (i) and / or (ii) comprises nucleic acid sequencing.

[0128] In some embodiments of any of the aspects, the nucleic acid sequencing comprises 16S metagenomic sequencing, shotgun metagenomic sequencing, and / or amplification and sequencing of the 16S gene by polymerase chain reaction and sequencing.

[0129] In some embodiments of any of the aspects, quantification of (i) and / or (ii) comprises non- scqucncing-bascd methods.

[0130] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifiaciens, B. caccae, B. caecicola, B. caecigallinarum, B. cellulosilyticus, B. cellulosolvens, B. clarus, B. coagulans, B. coprocola, B. coprophilus, B. coprosuis, B. dorei. B. eggerlhii, B. fiaecichinchillae, B. fiaecis, B. finegoldii, B. fluxus, B. fragilis, B. galacturonicus, B. gallinaceum, B. gallinarum, B. goldsteinii. B. graminisolvens, B. helcogene, B. intestinalis, B. luti, B. massiliensis, B. nordii, B. oleiciplenus, B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifaciens, B. putredinis, B. pyogenes, B. reticulotermitis, B. rodentium, B. salanitronis. B. salyersiae, B. sartorii, B. stercoris, B. thetaiotaomicron, B. uniformis. B. vulgatus. and B. xylanisolvens.|001311 In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing. and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides by at least 1% in the gut of the mammalian subject.

[0132] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.

[0133] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject.

[0134] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.

[0135] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) treats or improves symptoms of a mental disease or disorder.

[0136] In some embodiments of any of the aspects, the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's. Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

[0137] In some embodiments of any of the aspects, treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder.

[0138] In some embodiments of any of the aspects, at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts ofsuicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

[0139] In some embodiments of any of the aspects, the method further comprises administering at least one mood-improving therapeutic to the subject.

[0140] In some embodiments of any of the aspects, the method further comprises administering at least one anti-depression, anti-anxiety, and / or anti-stress therapeutic to the subject.

[0141] In some embodiments of any of the aspects, the method further comprises identifying a subject in need of treatment by determining whether the subject would benefit from an increase in endogenous GABA and / or GABA-producing bacteria by measuring an initial amount of GABA in the subject's stool.

[0142] In some embodiments of any of the aspects, the initial amount of endogenous GABA in the subject's stool is below about 300 pg per gram (pg / g), about 200 pg / g, about 100 pg / g, about 50 pg / g, about 20 pg / g, or about 10 pg / g of wet or dry stool.

[0143] In some embodiments of any of the aspects, the amount of GABA in the subject's stool is increased relative to the initial amount after administering the maltitol formulation.

[0144] In some embodiments of any of the aspects, the method further comprises identifying a subject in need of treatment by determining whether the subject would benefit from an increase in endogenous GABA by’ measuring an initial amount of GABA-producing bacteria in the subject's stool.

[0145] In some embodiments of any of tire aspects, the initial amount of GABA-producing bacteria in the subject's stool is less than about 50%, about 40%, about 30%, about 20%, about 10%, about 5%, or about 1% of total bacteria as measured by 16S sequence mapping.

[0146] In some embodiments of any of the aspects, the amount of GABA-producing bacteria in the subject's stool is increased relative to the initial amount after administering the maltitol formulation.

[0147] In some embodiments of any of the aspects, the GABA-producing bacteria are selected from Table 5, Table 6, Table 11 (e.g., “increased" column), Table 12, or Table 13.

[0148] In some embodiments of any of the aspects, the GABA-producing bacteria encode or express a protein or protein complex that internalizes and / or metabolizes maltitol selected from Table 9 or Table 10.

[0149] In some embodiments of any of the aspects, the GABA-producing bacteria comprise at least one bacterium of the genus Bacteroides.

[0150] In one aspect, described herein is a prebiotic composition as described herein, wherein the prebiotic composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the prebiotic composition is for the use of any one of the methods as described herein.

[0151] In one aspect, described herein is a synbiotic composition as described herein, wherein the synbiotic composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the synbiotic composition is for the use of any one of the methods as described herein.

[0152] In one aspect, described herein is a nutritional supplement as described herein, wherein the nutritional supplement is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the nutritional supplement is for the use of any one of the methods as described herein.

[0153] In one aspect, described herein is a food composition as described herein, wherein the food composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the food composition is for the use of any one of the methods as described herein.

[0154] In one aspect, described herein is a medical food as described herein, wherein the medical food is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the medical food is for the use of any one of the methods as described herein.

[0155] In one aspect, described herein is a pharmaceutical composition as described herein, wherein the pharmaceutical composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the pharmaceutical composition is for the use of any one of the methods as described herein.

[0156] A prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein for use in a method of improving mood in a mammalian subject.

[0157] In one aspect, described herein is a prebiotic composition as described herein, a sy nbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein for use in a method of promoting relaxation and / or promoting a calming mood state in a mammalian subject.

[0158] In one aspect, described herein is a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein for use in a method of reducing stress or anxiety in a mammalian subject.

[0159] In one aspect, described herein is a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as describedherein for use in a method of increasing the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject.

[0160] In one aspect, described herein is a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein for use in a method of increasing the production rate of y-aminobutyric acid (GABA) by at least one maltitol-intemalizing. and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, and / or increasing the concentration of y- aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a mammalian subject.

[0161] In one aspect, described herein is a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein for use in a method of treating depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0162] Fig. 1A-1D are a series of bar graphs showing levels of gut bacteria in response to various sweeteners and controls (untreated). Fig. 1A-1B shows the change in the percent relative abundance of (Fig. 1A) Bacteroides or (Fig. IB) Enterobacteriaceae in gut simulator communities derived from Donors 1 and 2 treated with a representative sweetener panel compared to control communities. Each point represents one replicate with the bar height indicating the mean and error bars representing the standard deviation. The represented statistics are a summary of statistical significance that was determined using a (Fig. 1A) One-Way ANOVA with Tukcy’s Multiple Comparison test on the relative abundance of Bacteroides values comparing each mean of treated communities to the mean of die control communities and the mean of communities treated with tw ice the dose of each sweetener for each donor or (Fig. IB) using a Student's T-Test comparing control versus treated communities (*= p<0.05, **= p<0.01, ***=p<0.001, ****= p<0.0001). Fig. 1C shows the percent change in relative abundance of Bacteroides in a human gut simulator treated with maltitol in an expanded donor panel to include Donors 3, 4, 5, and 6. Each point represents one replicate with the bar height indicating the mean and error bars representing the standard deviation. The represented statistics are a summary of statistical significance that was determined using a One-Way ANOVA with Dunned’ sMultiple Comparison test on the relative abundance of Bactcroidcs values comparing each mean of treated communities to the mean of the control for each donor (*= p<0.05, **= p<0.01, ***=p<0.001). Fig. ID shows the percent change in relative abundance of Enterobacteriaceae in a human gut simulator treated with maltitol in all donors. Each point represents one replicate with the bar height indicating the mean and error bars representing the standard deviation. The represented statistics are a summary of statistical significance that was determined using a Student’s T-test on the relative abundance of Enterobacteriaceae values comparing each mean of treated communities to the mean of the control for each donor (*= p<0.05, **= p<0.01).

[0163] Fig. 2 shows the relative abundance of Clostridium in gut simulator communities derived from Donor 2 treated with inositol or control. Each point represents one replicate with the bar height indicating the mean and error bars representing the standard deviation. Significance was determined using a Student’s T-Test comparing control versus inositol treated communities (**= p<0.01).

[0164] Fig. 3A-3B are a series of bar graphs showing levels of y- Aminobutyric acid (GABA). Fig. 3A shows the percent change in the concentration of GABA compared to the average concentration in control samples in gut simulator communities derived from six Human Donors (HD) treated with maltitol; the percent change reported represents the largest change observed under a single pH condition tested (5.0. 5.5. 6.0. 6.5. or 7.0). Each point represents the average percent change across two replicates. GABA levels were measured by liquid chromatography-mass spectrometry (LC / MS). Statistical significance was determined using a Student’s T-Test comparing the absolute GABA concentrations in a maltitol-treated community versus the control respectively for each donor (*= p<0.05, **= p<0.01, ****= p<0.0001). Fig. 3B shows the concentration of GABA at 48 hours in gut simulator communities derived from Donors 1, 2, 3, 4, 5. and 6 at pH 5.0, 5.5, 6.0. 6.5. Each point represents a single replicate. GABA levels were measured by LC / MS. Statistical significance was determined using a Student’s T-Test (**= p<0.01).DETAILED DESCRIPTION

[0165] Embodiments of the technology' described herein include compositions comprising an amount of maltitol effective to increase or decrease the relative and / or absolute abundance of at least one bacterium. The compositions can be prebiotic compositions, symbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions. The increase in die relative and / or absolute abundance of at least one bacterium can lead to an increased production rate and / or concentration of y-aminobutyric acid (GABA) in the subject, thus improving the mood and / or reducing stress or anxiety in the subject.

[0166] Also described herein are methods of using such compositions, such as to improve mood, promote relaxation, promote a calming mood state, reduce stress or anxiety, increase the relative abundance, absolute abundance, growth rate, metabolic activity', proportion, and / or concentration of atleast one bacterial species, and / or to increase the production rate and / or concentration of y- aminobutyric acid (GABA). Also described herein are methods of treating depression, anxiety, stress, and / or other mental health disorders.Compositions

[0167] Described herein in multiple aspects are compositions comprising an effective amount of maltitol. The compositions can be prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions comprising an amount of maltitol effective to increase the relative and / or absolute abrmdance of the at least one bacterium (e.g., of the genus Bacteroides or of the genus Bifidobacterium) and / or decrease the relative and / or absolute abundance of the at least one bacterium (e.g.. of the family Enterobacteriaceae) in the gut of the mammalian subject.

[0168] In some embodiments of any of tire aspects, the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) comprises an amount of maltitol effective to selectively modulate or increase / decrease the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one microbial species. In some embodiments of any of the aspects, the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) comprises an amount of maltitol effective to selectively increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of a desired microbial population or species without an increase in the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of an undesirable microbial population or species. In some embodiments of any of the aspects, the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) comprises an amount of maltitol effective to selectively increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of a desired microbial population or species with a concomitant decrease in the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of an undesirable microbial population or species.

[0169] In one aspect, described herein is a prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bacteroides in the gut of a mammalian subject relative to a control. In some embodiments of any of the aspects, the prebiotic composition comprises an amount of maltitol effective to increase the relative and / or absolute abundance of the at least one bacterium of the genus Bacteroides in the gut of the mammalian subject. In some embodiments of any of the aspects, the relative and / or absolute abundance of the at least onebacterium of the genus Bacteroides in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control (e.g., not consuming a prebiotic composition comprising an effective amount of maltitol).

[0170] In one aspect, described herein is a prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject relative to a control. In some embodiments of any of the aspects, the prebiotic composition comprises an amount of maltitol effective to increase relative abundance of the at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject. In some embodiments of any of the aspects, the relative and / or absolute abundance of the at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control (e.g.. not consuming a prebiotic composition comprising an effective amount of maltitol).

[0171] In one aspect, described herein is a prebiotic composition for decreasing the relative and / or absolute abundance of at least one bacterium of the family Enterobacteriaceae in the gut of a mammalian subject. In some embodiments of any of the aspects, the prebiotic composition comprises an amount of maltitol effective to decrease the relative and / or absolute abundance of the at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject. In some embodiments of any of the aspects, the relative and / or absolute abundance of the at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject compared to other formulations containing a sweetener that is not maltitol.

[0172] In one aspect, described herein is a synbiotic composition comprising a prebiotic composition as described herein and at least one bacterial species as described herein. In one aspect, described herein is a synbiotic composition comprising maltitol and at least one bacterial species as described herein. Further non-limiting examples of such synbiotic compositions arc provided herein.

[0173] In one aspect, described herein is a nutritional supplement comprising a prebiotic composition as described herein and / or a synbiotic composition as described herein. Further non-limiting examples of such nutritional supplements are provided herein.

[0174] In one aspect, described herein is a food composition comprising a prebiotic composition as described herein and / or a synbiotic composition as described herein. Further non-limiting examples of such food compositions are provided herein.

[0175] In one aspect, described herein is a pharmaceutical composition comprising a prebiotic composition as described herein and / or a synbiotic composition as described herein and a pharmaceutically acceptable carrier. Further non-limiting examples of such pharmaceutical compositions are provided herein.

[0176] The compositions described herein (e g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions comprising an amount of maltitol) can be taken by a subject or administered to a subject daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or more, for example, up to lifetime use.Maltitol

[0177] In multiple aspects, described herein are prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions comprising an amount of maltitol. Maltitol (also referred to interchangeably as CI-H-MO; i ; 4-O-a- glucopyranosyl-D-sorbitol; trade names LESYS, MALTISWEET, SWEETPEARL.) is shown in Formula I below.Formula I: Maltitol

[0178] Maltitol is a sugar alcohol, known as a polyol, primarily utilized as a sugar substitute. Structurally similar to sugar but with fewer calories, maltitol is a water-soluble white crystalline powder, highly soluble in water, with a slightly sweet taste and good texture. Maltitol reaches the colon primarily undigested, which is an aspect of its prebiotic ability.

[0179] In some embodiments of any of tire aspects, the effective amount of maltitol is comprised by a unit amount of the prebiotic composition. In some embodiments of any of the aspects, the effective amount of maltitol in any composition as described herein is a concentration of at least 1% to at most 100% w / w (weight concentration) maltitol. When polyols are used at greater than 10% by weight in the final product, the label can include the following statement “excessive consumption may produce laxative effects.” In some embodiments of any of tire aspects, the effective amount of maltitol is atmost 10% w / w. In some embodiments of any of the aspects, the effective amount of maltitol is at most 60% w / w.

[0180] As a non-limiting example, a composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises at least 1%, at least 2%. at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%. at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%. at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%. at least 23%, at least 24%, at least 25%, at least 26%, at least 27%. at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%. at least 35%, at least 36%, at least 37%. at least 38%, at least 39%, at least 40%, at least 41%, at least 42%. at least 43%, at least 44%, at least 45%, at least 46%. at least 47%, at least 48%, at least 49%. at least 50%, at least 51%, at least 52%. at least 53%, at least 54%. at least 55%, at least 56%, at least 57%. at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%. at least 76%, at least 77%. at least 78%, at least 79%, at least 80%. at least 81%, at least 82%, at least 83%. at least 84%, at least 85%. at least 86%, at least 87%, at least 88%. at least 89%, at least 90%, at least 91%, at least 92%. at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99% w / w (weight concentration) or more maltitol. In some embodiments of any of the aspects, the composition does not encompass pure (100%) maltitol.

[0181] As a non-limiting example, a composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%. about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%. about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%. about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%. about 69%, about 70%, about 71%. about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%. about 81%, about 82%, about 83%, about 84%, about 85%. about 86%, about 87%, about 88%. about 89%, about 90%, about 91%, about 92%, about 93%, about 94%. about 95%, about 96%, about 97%. about 98%, about 99% w / w (weight concentration), or more, maltitol.100182] As a non-limiting example, any composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / orpharmaceutical compositions) comprises at most 1%, at most 2%, at most 3%, at most 4%, at most 5%, at most 6%, at most 7%, at most 8%, at most 9%, at most 10%, at most 11%, at most 12%, at most 13%, at most 14%, at most 15%, at most 16%, at most 17%, at most 18%, at most 19%, at most 20%, at most 21%, at most 22%, at most 23%, at most 24%, at most 25%, at most 26%, at most 27%, at most 28%, at most 29%, at most 30%, at most 31%, at most 32%, at most 33%, at most 34%, at most 35%, at most 36%, at most 37%, at most 38%, at most 39%, at most 40%, at most 41%, at most 42%, at most 43%, at most 44%, at most 45%, at most 46%, at most 47%, at most 48%, at most 49%, at most 50%, at most 51%, at most 52%, at most 53%. at most 54%, at most 55%. at most 56%, at most 57%, at most 58%, at most 59%, at most 60%, at most 61%, at most 62%, at most 63%, at most 64%, at most 65%, at most 66%, at most 67%, at most 68%, at most 69%, at most 70%, at most 71%, at most 72%, at most 73%. at most 74%, at most 75%. at most 76%, at most 77%. at most 78%, at most 79%, at most 80%. at most 81%, at most 82%. at most 83%, at most 84%. at most 85%, at most 86%, at most 87%, at most 88%, at most 89%, at most 90%, at most 91%, at most 92%, at most 93%, at most 94%. at most 95%, at most 96%. at most 97%, at most 98%. at most 99% w / w (weight concentration), or more maltitol.

[0183] In some embodiments of any of tire aspects, the effective amount of maltitol is 0.5g to 25g per unit or serving. In some embodiments of any of the aspects, the effective amount of maltitol is 0.5g to 12g per unit or serving. In some embodiments of any of the aspects, the effective amount of maltitol is 7.2g per unit or serving. As a non-limiting example, a composition as described herein (e.g., prebiotic compositions, symbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises at least 0.5g, at least 0.6g, at least 0.7g, at least 0.8g, at least 0.9g, at least 1g, at least 1.1g, at least 1.2g. at least 1.3g, at least 1.4g, at least 1.5g, at least 1.6g, at least 1.7g, at least 1.8g. at least 1.9g, at least 2g, at least 2.1g, at least 2.2g, at least 2.3g, at least 2.4g, at least 2.5g, at least 2.6g, at least 2.7g, at least 2.8g, at least 2.9g, at least 3g, at least 3.1g. at least 3.2g, at least 3.3g, at least 3.4g, at least 3.5g, at least 3.6g, at least 3.7g, at least 3.8g, at least 3.9g, at least 4g, at least 4.1g, at least 4.2g, at least 4.3g, at least 4.4g. at least 4.5g, at least 4.6g, at least 4.7g. at least 4.8g, at least 4.9g, at least 5g. at least 5.1g, at least 5.2g, at least 5.3g, at least 5.4g. at least 5.5g, at least 5.6g, at least 5.7g, at least 5.8g. at least 5.9g, at least 6g, at least 6.1g. at least 6.2g, at least 6.3g, at least 6.4g. at least 6.5g, at least 6.6g, at least 6.7g. at least 6.8g, at least 6.9g, at least 7g, at least 7.1g, at least 7.2g, at least 7.3g. at least 7.4g, at least 7.5g, at least 7.6g, at least 7.7g. at least 7.8g, at least 7.9g, at least 8g. at least 8.1g. at least 8.2g, at least 8.3g, at least 8.4g. at least 8.5g, at least 8.6g. at least 8.7g. at least 8.8g, at least 8.9g, at least 9g. at least 9.1g, at least 9.2g, at least 9.3g, at least 9.4g, at least 9.5g, at least 9.6g, at least 9.7g, at least 9.8g, at least 9.9g, at least 10g, at least 10.1g, at least 10.2g, at least 10.3g, at least 10.4g, at least 10.5g, at least 10.6g, at least 10.7g, at least 10.8g, at least 10.9g, at least 11g, at least 11.1g, at least 11.2g. at least 11.3g. at least 11.4g, at least 1 1.5 g, at least 11 ,6g, at least 1 1.7g. at least 1 1.8g. at least 1 1.9g, at least 12g, at least 12.1 g, atleast 12.2g, at least 12.3g, at least 12.4g, at least 12.5g, at least 12.6g, at least 12.7g, at least 12.8g, at least 12.9g, at least 13g, at least 13.1g, at least 13.2g, at least 13.3g, at least 13.4g, at least 13.5g, at least 13.6g, at least 13.7g, at least 13.8g, at least 13.9g, at least 14g, at least 14.1g, at least 14.2g, at least 14.3g, at least 14.4g, at least 14.5g, at least 14.6g, at least 14.7g. at least 14.8g, at least 14.9g, at least 15g, at least 15.1g, at least 15.2g, at least 15.3g, at least 15.4g, at least 15.5g. at least 15.6g, at least 15.7g, at least 15.8g, at least 15.9g, at least 16g, at least 16.1g, at least 16.2g. at least 16.3g, at least 16.4g, at least 16.5g, at least 16.6g, at least 16.7g, at least 16.8g. at least 16.9g, at least 17g, at least 17.1g, at least 17.2g, at least 17.3g, at least 17.4g, at least 17.5g. at least 17.6g. at least 17.7g, at least 17.8g, at least 17.9g, at least 18g, at least 18.1g, at least 18.2g, at least 18.3g. at least 18.4g. at least 18.5g, at least 18.6g, at least 18.7g, at least 18.8g, at least 18.9g. at least 19g. at least 19.1g. at least 19.2g, at least 19.3g, at least 19.4g, at least 19.5g, at least 19.6g. at least 19.7g. at least 19.8g. at least 19.9g, at least 20g, at least 20.1g, at least 20.2g, at least 20.3g, at least 20.4g. at least 20.5g. at least 20.6g, at least 20.7g, at least 20.8g, at least 20.9g, at least 21g, at least 21.1g. at least 21.2g, at least 21.3g, at least 21.4g, at least 21.5g, at least 21.6g. at least 21.7g, at least 21.8g, at least 21.9g, at least 22g, at least 22.1g, at least 22.2g. at least 22.3g. at least 22.4g. at least 22.5g, at least 22.6g, at least 22.7g, at least 22.8g, at least 22.9g. at least 23g. at least 23.1g. at least 23.2g, at least 23.3g, at least 23.4g, at least 23.5g, at least 23.6g. at least 23.7g. at least 23.8g, at least 23.9g, at least 24g, at least 24.1g, at least 24.2g, at least 24.3g, at least 24.4g. at least 24.5g, at least 24.6g, at least 24.7g, at least 24.8g, at least 24.9g, or 25g maltitol per unit or serving.

[0184] As a non-limiting example, a composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises about 0.5g, about 0.6g, about 0.7g, about 0.8g, about 0.9g, about 1g, about 1.1g. about 1.2g, about 1.3g, about 1.4g, about 1.5g, about 1.6g, about 1.7g, aboutI.8g, about 1.9g, about 2g, about 2.1g, about 2.2g, about 2.3g, about 2.4g, about 2.5g, about 2.6g, about 2.7g, about 2.8g, about 2.9g, about 3g, about 3.1g, about 3.2g, about 3.3g, about 3.4g, about 3.5g, about 3.6g, about 3.7g, about 3.8g, about 3.9g, about 4g, about 4.1g, about 4.2g, about 4.3g, about 4.4g, about 4.5g, about 4.6g, about 4.7g, about 4.8g, about 4.9g, about 5g, about 5.1g, about 5.2g, about 5.3g, about 5.4g, about 5.5g, about 5.6g, about 5.7g, about 5.8g. about 5.9g, about 6g, about 6.1g, about 6.2g. about 6.3g, about 6.4g, about 6.5g, about 6.6g, about 6.7g, about 6.8g, about 6.9g, about 7g, about 7.1g, about 7.2g, about 7.3g. about 7.4g, about 7.5g, about 7.6g, about 7.7g, about 7.8g, about 7.9g. about 8g, about 8.1g, about 8.2g, about 8.3g, about 8.4g, about 8.5g, about 8.6g, about 8.7g, about 8.8g, about 8.9g, about 9g. about 9.1g, about 9.2g, about 9.3g, about 9.4g, about 9.5g, about 9.6g. about 9.7g, about 9.8g, about 9.9g, about 10g. about 10.1g, about 10.2g, about 10.3g, about 10.4g, about 10.5g, about 10.6g, about 10.7g. about 10.8g. about 10.9g, about 11g, aboutI I.1g, about 11.2g, about 11.3g, about 11.4g, about 11.5g. about 11.6g. about 11.7g, about 11.8g, about 11.9g. about 12g, about 12.1g, about 12.2g, about 12.3g. about 12.4g. about 12.5g, about 12.6g,about 12.7g, about 12.8g, about 12.9g, about 13g, about 13.1g, about 13.2g, about 13.3g, about 13.4g, about 13.5g, about 13.6g, about 13.7g, about 13.8g, about 13.9g, about 14g, about 14.1g, about 14.2g, about 14.3g. about 14.4g, about 14.5g, about 14.6g, about 14.7g, about 14.8g, about 14.9g, about 15g, about 15.1g. about 15.2g, about 15.3g, about 15.4g, about 15.5g, about 15.6g, about 15.7g, about 15.8g, about 15.9g, about 16g, about 16.1g, about 16.2g, about 16.3g, about 16.4g, about 16.5g, about 16.6g, about 16.7g, about 16.8g, about 16.9g, about 17g, about 17.1g, about 17.2g, about 17.3g, about 17.4g, about 17.5g, about 17.6g, about 17.7g, about 17.8g, about 17.9g. about 18g, about 18.1g, about 18.2g, about 18.3g, about 18.4g, about 18.5g, about 18.6g, about 18.7g. about 18.8g, about 18.9g, about 19g, about 19.1g, about 19.2g, about 19.3g, about 19.4g. about 19.5g. about 19.6g, about 19.7g, about 19.8g. about 19.9g, about 20g, about 20.1g, about 20.2g. about 20.3g. about 20.4g, about 20.5g, about 20.6g. about 20.7g, about 20.8g, about 20.9g, about 21g. about 21.1g. about 21.2g, about 21.3g, about 21.4g. about 21.5g, about 21.6g, about 21.7g, about 21.8g. about 21.9g. about 22g, about 22.1g, about 22.2g. about 22.3g, about 22.4g, about 22.5g, about 22.6g, about 22.7g, about 22.8g, about 22.9g, about 23g, about 23.1g, about 23.2g, about 23.3g, about 23.4g, about 23.5g, about 23.6g, about 23.7g. about 23.8g. about 23.9g. about 24g, about 24.1g, about 24.2g. about 24.3g. about 24.4g. about 24.5g. about 24.6g. about 24.7g, about 24.8g, about 24.9g, or about 25g maltitol per unit or serving.

[0185] As a non-limiting example, a composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises at most 0.5g, at most 0.6g, at most 0.7g, at most 0.8g. at most 0.9g. at most 1g, at most 1.1g, at most 1.2g, at most 1.3g, at most 1.4g, at most 1.5g, at most1.6g, at most 1.7g, at most 1.8g, at most 1.9g, at most 2g, at most 2.1g, at most 2.2g, at most 2.3g, at most 2.4g. at most 2.5g, at most 2.6g, at most 2.7g, at most 2.8g, at most 2.9g, at most 3g, at most 3.1g, at most 3.2g, at most 3.3g, at most 3.4g, at most 3.5g, at most 3.6g, at most 3.7g, at most 3.8g, at most 3.9g, at most 4g, at most 4.1g, at most 4.2g, at most 4.3g, at most 4.4g, at most 4.5g, at most4.6g, at most 4.7g, at most 4.8g, at most 4.9g, at most 5g, at most 5.1g, at most 5.2g, at most 5.3g, at most 5.4g, at most 5.5g, at most 5.6g, at most 5.7g, at most 5.8g, at most 5.9g, at most 6g, at most 6.1g, at most 6.2g, at most 6.3g, at most 6.4g, at most 6.5g, at most 6.6g, at most 6.7g, at most 6.8g, at most 6.9g, at most 7g, at most 7.1g. at most 7.2g, at most 7.3g, at most 7.4g, at most 7.5g, at most 7.6g, at most 7.7g, at most 7.8g, at most 7.9g, at most 8g, at most 8.1g, at most 8.2g, at most 8.3g, at most 8.4g, at most 8.5g, at most 8.6g, at most 8.7g, at most 8.8g, at most 8.9g, at most 9g, at most 9.1g, at most 9.2g. at most 9.3g, at most 9.4g, at most 9.5g, at most 9.6g, at most 9.7g. at most 9.8g, at most 9.9g, at most 10g, at most 10.1g, at most 10.2g, at most 10.3g, at most 10.4g, at most 10.5g, at most 10.6g, at most 10.7g, at most 10.8g, at most 10.9g, at most 11g, at most 11.1g, at most 11.2g, at most 11.3g, at most 11.4g, at most 11.5g, at most 11.6g, at most 11.7g, at most 11.8g, at most 11.9g, at most 12g. at most 12.1g. at most 12.2g. at most 12.3g. at most 12.4g. at most 12.5g. at most 12.6g. at most 12.7g. at most 12.8g. at most 12.9g. at most 13g. at most 13.1g. at most 13.2g. at most 13.3g.at most 13.4g, at most 13.5g, at most 13.6g, at most 13.7g, at most 13.8g, at most 13.9g, at most 14g, at most 14.1g, at most 14.2g, at most 14.3g, at most 14.4g, at most 14.5g, at most 14.6g, at most 14.7g, at most 14.8g, at most 14.9g, at most 15g, at most 15.1g, at most 15.2g, at most 15.3g, at most 15.4g, at most 15.5g, at most 15.6g, at most 15.7g, at most 15.8g, at most 15.9g, at most 16g, at most 16.1g, at most 16.2g, at most 16.3g, at most 16.4g, at most 16.5g, at most 16.6g, at most 16.7g, at most 16.8g, at most 16.9g, at most 17g, al most 17.1g, al most 17.2g, al most 17.3g, al most 17.4g, at most 17.5g, al most 17.6g, al most 17.7g, al most 17.8g, al most 17.9g, at most 18g, al most 18.1g, at most 18.2g, al most 18.3g, al most 18.4g, al most 18.5g, al most 18.6g, al most 18.7g, al most 18.8g, al most 18.9g. al most 19g. at most 19.1g. at most 19.2g. at most 19.3g. at most 19.4g. at most 19.5g. at most 19.6g. at most 19.7g. at most 19.8g. at most 19.9g. at most 20g. at most 20.1g. at most 20.2g. at most 20.3g. at most 20.4g. at most 20.5g. at most 20.6g. at most 20.7g. at most 20.8g. at most 20.9g, at most 21g, at most 21.1g, at most 21.2g, at most 21.3g, at most 21.4g, at most 21.5g, at most 21.6g, at most 21.7g, at most 21.8g, at most 21.9g, at most 22g, at most 22.1g, at most 22.2g, at most 22.3g, at most 22.4g, at most 22.5g, at most 22.6g, at most 22.7g, at most 22.8g, at most 22.9g, at most 23g, al most 23.1g, al most 23.2g, at most 23.3g, at most 23.4g, at most 23.5g, at most 23.6g, at most 23.7g, at most 23.8g, at most 23.9g, at most 24g, at most 24.1g, at most 24.2g, at most 24.3g, at most 24.4g, at most 24.5. at most 24.6g. at most 24.7g. at most 24.8g. at most 24.9g. or at most 25g maltitol per unit or serving.

[0186] In some embodiments of any of tire aspects, the effective amount of maltitol in any composition as described herein is a concentration of at least 1 g / L to at most 100 g / L maltitol. In some embodiments of any of the aspects, the effective amount of maltitol in any composition as described herein is a concentration of about 9 g / L maltitol.

[0187] As a non-limiting example, a composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises at least 1 g / L, at least 2 g / L, at least 3 g / L, at least 4 g / L, at least 5 g / L, at least 6 g / L, at least 7 g / L, at least 8 g / L, at least 9 g / L, at least 10 g / L, at least 11 g / L, at least 12 g / L. at least 13 g / L, at least 14 g / L, at least 15 g / L, at least 16 g / L, at least 17 g / L, at least 18 g / L, at least 19 g / L, at least 20 g / L, at least 21 g / L, at least 22 g / L, at least 23 g / L, at least 24 g / L. at least 25 g / L. at least 26 g / L, at least 27 g / L, at least 28 g / L. at least 29 g / L, at least 30 g / L, at least 31 g / L, at least 32 g / L, at least 33 g / L, at least 34 g / L, at least 35 g / L, at least 36 g / L, at least 37 g / L. at least 38 g / L. at least 39 g / L, at least 40 g / L, at least 41 g / L. at least 42 g / L, at least 43 g / L, at least 44 g / L, at least 45 g / L, at least 46 g / L, at least 47 g / L, at least 48 g / L, at least 49 g / L, at least 50 g / L. at least 51 g / L. at least 52 g / L, at least 53 g / L, at least 54 g / L. at least 55 g / L, at least 56 g / L, at least 57 g / L, at least 58 g / L, at least 59 g / L, at least 60 g / L, at least 61 g / L, at least 62 g / L, at least 63 g / L, at least 64 g / L. at least 65 g / L, at least 66 g / L, at least 67 g / L. at least 68 g / L, at least 69 g / L, at least 70 g / L, at least 71 g / L, at least 72 g / L. at least 73 g / L, at least 74 g / L, at least 75 g / L. at least 76 g / L. atleast 77 g / L, at least 78 g / L, at least 79 g / L, at least 80 g / L, at least 81 g / L, at least 82 g / L, at least 83 g / L, at least 84 g / L, at least 85 g / L, at least 86 g / L, at least 87 g / L, at least 88 g / L, at least 89 g / L. at least 90 g / L. at least 91 g / L, at least 92 g / L, at least 93 g / L, at least 94 g / L, at least 95 g / L, at least 96 g / L, at least 97 g / L, at least 98 g / L, at least 99 g / L, or 100 g / L maltitol.

[0188] As a non-limiting example, a composition as described herein (e.g.. prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises about 1 g / L, about 2 g / L, about 3 g / L, about 4 g / L, about 5 g / L, about 6 g / L, about 7 g / L, about 8 g / L, about 9 g / L, about 10 g / L. about 11 g / L, about 12 g / L, about 13 g / L, about 14 g / L, about 15 g / L, about 16 g / L, about 17 g / L. about 18 g / L, about 19 g / L, about 20 g / L, about 21 g / L, about 22 g / L, about 23 g / L, about 24 g / L. about 25 g / L, about 26 g / L, about 27 g / L, about 28 g / L, about 29 g / L. about 30 g / L, about 31 g / L. about 32 g / L, about 33 g / L, about 34 g / L, about 35 g / L, about 36 g / L. about 37 g / L, about 38 g / L. about 39 g / L. about 40 g / L, about 41 g / L, about 42 g / L, about 43 g / L, about 44 g / L, about 45 g / L, about 46 g / L, about 47 g / L, about 48 g / L, about 49 g / L. about 50 g / L, about 51 g / L, about 52 g / L, about 53 g / L, about 54 g / L, about 55 g / L. about 56 g / L. about 57 g / L, about 58 g / L. about 59 g / L, about 60 g / L, about 61 g / L. about 62 g / L, about 63 g / L. about 64 g / L, about 65 g / L, about 66 g / L, about 67 g / L, about 68 g / L. about 69 g / L, about 70 g / L. about 71 g / L, about 72 g / L, about 73 g / L, about 74 g / L, about 75 g / L. about 76 g / L, about 77 g / L. about 78 g / L, about 79 g / L, about 80 g / L, about 81 g / L, about 82 g / L, about 83 g / L, about 84 g / L. about 85 g / L, about 86 g / L, about 87 g / L, about 88 g / L, about 89 g / L, about 90 g / L, about 91 g / L. about 92 g / L, about 93 g / L, about 94 g / L, about 95 g / L, about 96 g / L, about 97 g / L, about 98 g / L. about 99 g / L, or about 100 g / L maltitol.

[0189] As a non-limiting example, any composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) comprises at most 1 g / L, at most 2 g / L, at most 3 g / L, at most 4 g / L, at most 5 g / L, at most 6 g / L, at most 7 g / L, at most 8 g / L, at most 9 g / L, at most 10 g / L, at most 11 g / L, at most 12 g / L, at most 13 g / L, at most 14 g / L, at most 15 g / L, at most 16 g / L, at most 17 g / L, at most 18 g / L, at most 19 g / L. at most 20 g / L, at most 21 g / L, at most 22 g / L, at most 23 g / L, at most 24 g / L, at most 25 g / L, at most 26 g / L, at most 27 g / L, at most 28 g / L, at most 29 g / L, at most 30 g / L, at most 31 g / L, at most 32 g / L. at most 33 g / L, at most 34 g / L, at most 35 g / L, at most 36 g / L, at most 37 g / L, at most 38 g / L, at most 39 g / L, at most 40 g / L, at most 41 g / L, at most 42 g / L, at most 43 g / L, at most 44 g / L, at most 45 g / L. at most 46 g / L, at most 47 g / L. at most 48 g / L, at most 49 g / L, at most 50 g / L, at most 51 g / L, at most 52 g / L, at most 53 g / L, at most 54 g / L, at most 55 g / L, at most 56 g / L, at most 57 g / L, at most 58 g / L. at most 59 g / L, at most 60 g / L. at most 61 g / L, at most 62 g / L. at most 63 g / L, at most 64 g / L, at most 65 g / L, at most 66 g / L, at most 67 g / L, at most 68 g / L, at most 69 g / L, at most 70 g / L, at most 71 g / L. at most 72 g / L, at most 73 g / L. at most 74 g / L, at most 75 g / L. at most 76 g / L, at most 77 g / L, at most 78 g / L. at most 79 g / L, at most 80 g / L, at most 81 g / L, at most 82 g / L, at most83 g / L, at most 84 g / L, at most 85 g / L, at most 86 g / L, at most 87 g / L, at most 88 g / L, at most 89 g / L, at most 90 g / L, at most 91 g / L, at most 92 g / L, at most 93 g / L, at most 94 g / L, at most 95 g / L, at most 96 g / L, at most 97 g / L, at most 98 g / L, at most 99 g / L, or at most 100 g / L maltitol.

[0190] In some embodiments of any of the aspects, the form of maltitol in any composition as described herein (e.g., prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions) is selected from the group consisting of maltitol syrup, maltitol powder, maltitol crystals, and / or maltitol gel.

[0191] In some embodiments of any of the aspects, the maltitol syrup comprises about 5% sorbitol. As non-limiting examples, the maltitol syrup comprises about 1%, about 2%, about 3%, about 4%, about 5%. about 6%. about 7%, about 8%, about 9%, or about 10% sorbitol.Maltitol-lncreased Bacteria

[0192] In multiple aspects, described herein are prebiotic compositions comprising an effective amount of maltitol that can increase the relative and / or absolute abundance of at least one bacterium (e.g., 1, 2, 3. 4, 5, 6, 7, 8, 9. 10, 20, 30, 40, 50, 60, 70, 80, 90. 100, or more bacterial species) in a mammalian gut. In some embodiments, the growth rate, metabolic activity, proportion, and / or concentration of at least one bacterium is increased. In some embodiments, GABA production by at least one bacterium in the gut of the mammalian subject is increased (e.g., GABA-producing bacteria), and / or GABA concentration in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is increased. In some embodiments of any of the aspects, the at least one bacterium with increased relative and / or absolute abundance (or increased growth rate, metabolic activity, proportion, concentration, and / or GABA production) in the presence of a prebiotic composition comprising an effective amount of maltitol is selected from Table 5, Table 6, Table 11 (e.g., “increased” column), Table 12, or Table 13. Non-limiting examples of such bacteria include a bacterium from the genus Bacteroides or Bifidobacterium.

[0193] In multiple aspects, compositions described herein, including but not limited to synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmacal compositions comprise at least one bacterial species (e.g., 1, 2. 3. 4, 5, 6, 7, 8. 9, 10. 20, 30, 40, 50. 60, 70, 80, 90. 100, or more bacterial species), as described further herein.

[0194] In some embodiments of any of the aspects, the at least one bacterial species belongs to a bacterial species selected from the group consisting of Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum. Bifidobacterium dentium. Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium pseudoIongum, Bifidobacterium suis, Lactobacillus acidophilus, Lactobacillus brevis. Lactobacillus bulgaricus, Lactobacillus casei. Lactobacillus crispatus, Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus johnsonii. Lactobacillus paracasei. Lactobacillusplantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus sakei, and Lactobacillus gasseri, or a combination thereof.

[0195] In some embodiments of any of the aspects, die at least one bacterial species belongs to a bacterial strain selected from the group consisting of Bifidobacterium longum subsp. infantis, Bifidobacterium longum subsp. longum, and Bifidobacterium longum subsp. suillum, or a combination thereof.

[0196] In multiple aspects, compositions described herein, including but not limited to synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmacal compositions comprise at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species. In some embodiments of any of the aspects, at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species as described herein is selected from Table 5, Table 6, Table 11 (e.g.. “increased” column), Table 12, or Table 13.

[0197] In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is dried and / or viable. In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species is freeze-dried and / or spray -dried. In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species is a viable, isolated bacterial species.

[0198] In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is present at a concentration of at least 101colony forming units per gram (CFU / g) to at most 1013CFU / g. In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species is present at a concentration of about 101CFU / g, about 102CFU / g, about 103CFU / g, about 104CFU / g, about 10sCFU / g, about 106CFU / g, about 10 CFU / g, about 108CFU / g, about 109CFU / g, about 1010CFU / g, about 1011CFU / g, about 1012CFU / g, about 1013CFU / g, or more.

[0199] In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is at least one bacterium of the genus Bacteroides. In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides as described herein is selected from Table 5 or Table 6.

[0200] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifaciens, B. caccae, B. caecicola, B. caecigallinarum, B. cellulosilyticus, B. cellulosolvens, B. clarus, B. coagulans, B. coprocola, B. coprophilus, B. coprosuis, B. dorei. B. eggerthii, B. faecichinchillae, B. faecis, B. finegoldii, B. fiuxus, B. fragilis, B. galacturonicus, B. gallinaceum. B. gallinarum, B. goldsteinii. B. graminisolvens, B. helcogene, B. intestinalis, B. luti. B. massiliensis, B. nordii, B. oleiciplenus. B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifaciens. B. putredinis. B. pyogenes. B.reticulotermitis, B. rodentium, B. salanitronis, B. salyersiae, B. sartorii, B. stercoris, B. thetaiotaomicron, B. uniformis, B. vulgatus, and B. xylan i solve ns.

[0201] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides internalizes and / or metabolizes the maltitol in the composition in the gut of a mammalian subject.

[0202] In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species (e.g., a Bacteroides species) comprises a 16S sequence selected from Table 5. In some embodiments of any of the aspects, the at least one maltitol-intemalizing. and / or maltitol-metabolizing, and / or maltitol-supported bacterial species (e.g., a Bacteroides species) comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%. at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%, at least 99.99%, or more, identical to one of SEQ ID NOs: 1-45

[0203] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%. at least 99.99%, or more, identical to one of SEQ ID NOs: 1-45.

[0204] Table 5: Exemplary Bacteroides species - 16S Sequences

[0205] In some embodiments of any of die aspects, at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species (e.g., a Bacteroides species) comprises a genome selected from Table 6. In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species (e.g., a Bacteroides species) comprises a genome selected from Table 6 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%, at least 99.99%, or more, identical a genome selected from Table 6.

[0206] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides comprises a genome selected from Table 6or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%. at least 98%, at least 99%, at least 99.1%. at least 99.5%, at least 99.99%, or more, identical to a genome selected from Table 6.

[0207] Table 6: Exemplary Bacteroides species - Whole Genome Sequences (WGS)

[0208] In some embodiments of any of die aspects, at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species encodes and / or expresses a protein or protein complex that internalizes and / or metabolizes maltitol. In some embodiments of any of the aspects, a protein or protein complex that internalizes and / or metabolizes maltitol is selected from Table 9 or Table 10. In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides encodes and expresses a protein or protein complex that internalizes and / or metabolizes maltitol.

[0209] In some embodiments of any of the aspects, a protein or protein complex that internalizes and / or metabolizes maltitol comprises one of SEQ ID NOs: 179-295 or an amino acid sequence that is at least 70%, at least 75%, at least 80%. at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least99.1%, at least 99.5%, at least 99.99%, or more, identical to one of SEQ ID NOs: 179-295 that maintains its maltitol-intemalizing or maltitol-metabolizing function as a polypeptide.

[0210] In some embodiments of any of the aspects, the protein or protein complex that internalizes and / or metabolizes maltitol is maltitol dehydrogenase or a-glucosidase. In some embodiments of any of the aspects, a bacterium as described encodes and / or expresses a maltitol metabolism enzyme selected from Table 9. In some embodiments of any of the aspects, a protein or protein complex that metabolizes maltitol comprises one of SEQ ID NOs: 90-170 or an amino acid sequence that is at least 70%, at least 75%. at least 80%, at least 85%. at least 90%, at least 91%, at least 92%. at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%, at least 99.99%. or more, identical to one of SEQ ID NOs: 90-170 that maintains its maltitol- metabolizing function as a polypeptide.

[0211] Table 9: Exemplary maltitol metabolism enzymes - Polypeptide Sequences

[0212] In some embodiments of any of the aspects, a bacterium as described encodes and / or expresses a maltitol transporter selected from Table 10. In some embodiments of any of the aspects, a protein or protein complex that internalizes maltitol comprises one of SEQ ID NOs: 171-206 or an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%, at least 99.99%, or more, identical to one of SEQ ID NOs: 171-206 that maintains its maltitol-intemalizing function as a polypeptide.

[0213] Tabic 10: Exemplary maltitol transporters - Polypeptide Sequences

[0214] In some embodiments of any of the aspects, a bacterial species as described herein is selected from Table 11. In some embodiments of any of the aspects, at least one bacterium with increased relative and / or absolute abundance in the presence of a prebiotic composition comprising an effective amount of maltitol is selected from the “increased” column of Table 11.

[0215] Table 11: Exemplary bacteria that showed abundance modulated by maltitol. Table 11 shows Genera whose relative abundance were increased by at least 10% (i.e., a 10% increase or a 1.1- fold change) (see e.g., Tables 12-13) or decreased by at least 10% (i.e., a 10% decrease or a 0.9-fold- change) (see e.g.. Tables 14-15) in maltitol-treated gut simulator communities compared to control communities. Shifts were observed in at least 3 of 6 human donors.| Increased | Decreased |

[0216] In some embodiments of any of tire aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence selected from Table 12. In some embodiments of any of the aspects, the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence comprising one of SEQ ID NOs: 207-360 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%, at least 99.99%, or more, identical to one of SEQ ID NOs: 207-360.

[0217] Table 12: Exemplary bacterial species whose relative abundance was increased by at least 1.1 -fold by maltitol - 16S Sequences

[0218] In some embodiments of any of the aspects, at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 13. In some embodiments of any of the aspects, the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 13 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%. at least 94%, at least 95%, at least 96%, at least97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%, at least 99.99%, or more, identical to a genome selected from Table 13.

[0219] Table 13: Exemplary bacterial species whose relative abundance was increased by at least 1.1 -fold by maltitol - Whole Genome Sequences (WGS)

[0220] In some embodiments of any of the aspects, a combination of bacterial species as described herein is selected from Table 16. In some embodiments of any of the aspects, at least two bacteria with increased relative and / or absolute abundance in the presence of a prebiotic composition comprising an effective amount of maltitol is selected from the exemplary combinations shown in Table 16. In some embodiments of any of the aspects, a composition (e.g., a synbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein) comprises a combination of bacteria selected from Table 16.

[0221] Table 16: Exemplary Bacterial Combinations (e g., each combination comprising bacterium 1 and bacterium 2 in a row)Maltitol-Decreased Bacteria

[0222] In multiple aspects, described herein are prebiotic compositions comprising an effective amount of maltitol that can decrease the relative and / or absolute abundance of at least one bacterium (e.g., 1, 2, 3. 4. 5. 6, 7, 8, 9. 10, 20, 30, 40. 50, 60, 70, 80. 90. 100, or more bacterial species). In some embodiments, the growth rate, metabolic activity, proportion, and / or concentration of at least one bacterium is decreased. In some embodiments of any of the aspects, the at least one bacterium with decreased relative and / or absolute abundance in the presence of a prebiotic composition comprising an effective amount of maltitol is selected from Table 7, Table 8, Table 11 (e g., “decreased” column), Table 14, or Table 15. A non-limiting example of such a bacterium includes a bacterium of the family Enterobacteriaceae.

[0223] In some embodiments of any of the aspects, at least one bacterium of the family Enterobacteriaceae as described herein is selected from Table 7 or Table 8. In some embodiments of any of the aspects, the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence selected from Table 7. In some embodiments of any of the aspects, the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence comprising one of SEQ ID NOs: 46-89 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.5%, at least 99.99%, or more, identical to one of SEQ ID NOs: 46-89.

[0224] Table 7: Exemplary bacteria of the family Enterobacteriaceae - 16S Sequences

[0225] In some embodiments of any of the aspects, the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8. In some embodiments of any of the aspects, the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least97%, at least 98%. at least 99%, at least 99.1%, at least 99.5%, at least 99.99%, or more, identical to a genome selected from Table 8.

[0226] Table 8: Exemplary bacteria of the family Enterobacteriaceae - Whole GenomeSequences (WGS)

[0227] In some embodiments of any of the aspects, at least one bacterium with decreased relative and / or absolute abundance in the presence of a prebiotic composition comprising an effective amount of maltitol is selected from the “decreased” column of Table 11 . In some embodiments of any of the aspects, at least one bacterium with decreased relative and / or absolute abundance in the presence of a prebiotic composition comprising an effective amount of maltitol comprises a 16S sequence selected from Table 14, e.g., comprising one of SEQ ID NOs: 361-596 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%. at least 98%, at least 99%, at least 99.1%. at least 99.5%. at least 99.99%, or more, identical to one of SEQ ID NOs: 361-596.

[0228] Table 14: Exemplary bacterial species whose relative abundance was decreased by at least 0.9-fold by maltitol - 16S Sequences

[0229] In some embodiments of any of the aspects, at least one bacterium with decreased relative and / or absolute abundance in the presence of a prebiotic composition comprising an effective amount of maltitol comprises a genome selected from Table 15 or a nucleic acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 91%, at least 92%, at least 93%, at least94%, at least 95%. at least 96%, at least 97%. at least 98%, at least 99%, at least 99.1%. at least99.5%, at least 99.99%, or more, identical to a genome selected from Table 15.

[0230] Table 15: Exemplary bacterial species whose relative abundance was decreased by at least 0.9-fold by maltitol - Whole Genome Sequences (WGS)Prebiotic Compositions

[0231] In multiple aspects, described herein arc prebiotic compositions. In some embodiments of any of the aspects, the prebiotic composition comprises an amount of maltitol effective to selectively modulate or increase / decrease the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one microbial species. In some embodiments of any of the aspects, the prebiotic composition comprises an amount of maltitol effective to selectively increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of a desired microbial population or species without an increase in the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of an undesirable microbial population or species. In some embodiments of any of the aspects, the prebiotic composition comprises an amount of maltitol effective to selectively increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of a desired microbial population or species with a concomitant decrease in the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of an undesirable microbial population or species.

[0232] In one aspect, described herein is a prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bacteroides in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase tire relative and / or absolute abundance of the at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control. In some embodiments of any of the aspects, the effective amount of maltitol is described further herein.

[0233] In one aspect, described herein is a prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase relative abundance of the at least one bacterium of the genus Bifidobacterium in the gut ofdie mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control.

[0234] In one aspect, described herein is a prebiotic composition for decreasing the relative and / or absolute abundance of at least one bacterium of the family Enterobacteriaceae in the gut of a mammalian subject, the prebiotic composition comprising an amount of maltitol effective to decrease the relative and / or absolute abundance of the at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject compared to other formulations containing a sweetener that is not maltitol.

[0235] In some embodiments of any of the aspects, the prebiotic increases the relative and / or absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one bacterium selected from Table 5, Table 6. Table 11 (e.g., “increased” column), Table 12, or Table 13. In some embodiments of any of the aspects, the prebiotic decreases the relative and / or absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one bacterium selected from Table 7, Table 8. Table 11 (e.g., “decreased” column). Table 14. or Table 15.

[0236] In some embodiments of any of the aspects, at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium internalizes, is supported by, and / or metabolizes the effective amount of maltitol in the prebiotic composition in the prebiotic composition in the gut of the mammalian subject. In some embodiments of any of the aspects, the mammalian subject is a human.

[0237] In some embodiments of any of the aspects, the internalization and / or metabolization by or die support of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the prebiotic composition increases the relative and / or absolute abundance of the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the relative and / or absolute abundance can be increased by at least 1%, at least 2%. at least 3%, at least 4%, at least 5%, at least 10%, at least 20%, at least 30%. at least 40%, at least 50%, at least 60%, at least 70%, at least 80%. at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0238] In some embodiments of any of the aspects, the internalization and / or metabolization by or die support of die at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the prebiotic composition increases the growth rate and / or metabolic activity of the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the growth rate and / or metabolic activity can be increased by at least 1%. at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 20%, at least 30%. at least 40%, at least 50%, at least 60%. at least 70%, at least 80%, at least 90%. at least 100%. at least 200%. at least 300%. at least 400%. at least 500%. at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0239] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the prebiotic composition increases the proportion and / or concentration of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the proportion and / or concentration can be increased by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%. at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0240] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or by tire at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the prebiotic composition increases the production of y-ainiiiobutyric acid (GABA) by the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut, blood plasma or semm, cerebrospinal fluid, breast milk, or feces of the mammalian subject. As a non-limiting example, the production of y-aminobutyric acid (GABA) can be increased by at least 1%, at least 2%, at least 3%, at least 4%. at least 5%, at least 10%, at least 20%. at least 30%, at least 40%. at least 50%, at least 60%, at least 70%. at least 80%, atleast 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0241] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the prebiotic composition increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. As a nonlimiting example, the concentration of y-aminobutyric acid (GABA) can be increased by at least 1%. at least 2%, at least 3%, at least 4%, at least 5%. at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%. at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0242] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject. In some embodiments of any of the aspects, the increased production rate and / or concentration of y- aminobutyric acid (GABA) in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject. In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacteroides or the at least one bacterium of the genus Bifidobacterium in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder.

[0243] In some embodiments of any of the aspects, the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder). Neurodegenerative amyloid disorders (Parkinson's. Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

[0244] In some embodiments of any of the aspects, treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder. In some embodiments of any of the aspects, at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of selfharm, restlessness, low sex drive, lack of focus, seizures, memory' loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

[0245] In some embodiments of any of the aspects, the prebiotic composition further comprises at least one excipient (e.g., 1. 2. 3, 4, 5, 6, 7. 8, 9, 10, or more excipients). In some embodiments of any of the aspects, the at least one excipient is selected from the group consisting of encapsulation materials (e.g., chitosan, wax, and gelatin), solubilizers (e.g.. TWEEN 80 or SPAN 60), bulking agents (e.g., maltodextrin or microcrystalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g.. ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof.

[0246] In some embodiments of any of the aspects, the prebiotic composition further comprises at least one additional prebiotic (e.g., 1 , 2, 3. 4. 5, 6, 7, 8, 9. 10, or more prebiotics in addition to maltitol). In some embodiments of any of the aspects, the at least one additional prebiotic is selected from the group consisting of amino acid (e.g., arginine, glutarate, and ornithine), biotin, fructooligosaccharide, galactooligosaccharide, hemi cellulose (e.g., arabinoxylan, xylan, xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, gum (e.g., guar gum, gum arabic and carrageenan), oligofructose, oligodextrose, tagatose, resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide, pectin (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fiber (e.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccharidc, and polyaminc (e.g., spermidine, putrescine).

[0247] In some embodiments of any of the aspects, the prebiotic composition is formulated for delivery to the gut of a mammalian subject. In some embodiments of any of the aspects, the prebiotic composition is in the form of a symbiotic, a capsule, a tablet, a caplet, a pill, a troche, a candy, a syrup, an elixir, a lozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

[0248] The prebiotic supplements described herein can be taken by a subject daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks. 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or more, for example, up to lifetime use.Synbiotic Compositions

[0249] In multiple aspects, described herein are synbiotic compositions. In one aspect, described herein is a synbiotic composition comprising a prebiotic composition as described herein and at least one bacterial species as described herein. In one aspect, described herein is a synbiotic composition comprising maltitol and at least one bacterial species as described herein. In one aspect, described herein is a synbiotic composition comprising an effective amount of maltitol and at least one bacterial species as described herein. In one aspect, described herein is a synbiotic composition comprising an effective amount of maltitol and at least one bacterial species selected from Table 5, Table 6, Table 11 (e.g.. “increased” column), Table 12, or Table 13. In some embodiments of any of the aspects, the effective amount of maltitol is described further herein.|00250] In some embodiments of any of the aspects, the synbiotic composition comprises an amount of maltitol effective to selectively modulate or increase / decrease the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one microbial species. In some embodiments of any of the aspects, the synbiotic composition comprises an amount of maltitol effective to selectively increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of a desired microbial population or species without an increase in the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of an undesirable microbial population or species. In some embodiments of any of the aspects, the synbiotic composition comprises an amount of maltitol effective to selectively increase the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of a desired microbial population or species with a concomitant decrease in the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of an undesirable microbial population or species.

[0251] In some embodiments of any of the aspects, the sy nbiotic composition comprises an amount of maltitol effective to increase the growth rate and / or metabolic activity of at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when die prebiotic composition is consumed by the mammalian subject.

[0252] In some embodiments of any of the aspects, the synbiotic composition comprises an amount of maltitol effective to increase the growth rate and / or metabolic activity of at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject.

[0253] In some embodiments of any of the aspects, the synbiotic composition comprises an amount of maltitol effective to decrease the growth rate and / or metabolic activity of at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / orabsolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject.

[0254] In some embodiments of any of die aspects, at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium internalizes, is supported by, and / or metabolizes the effective amount of maltitol in the synbiotic composition in the gut of the mammalian subject. In some embodiments of any of the aspects, the mammalian subject is a human.

[0255] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the synbiotic composition increases the relative and / or absolute abundance of the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the relative and / or absolute abundance can be increased by at least 1%. at least 2%, at least 3%, at least 4%, at least 5%. at least 10%, at least 20%, at least 30%, at least 40%. at least 50%, at least 60%. at least 70%, at least 80%, at least 90%. at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%. or more.

[0256] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the synbiotic composition increases the growth rate and / or metabolic activity of the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the growth rate and / or metabolic activity can be increased by at least 1%. at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%. at least 100%. at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0257] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the synbiotic composition increases the proportion and / or concentration of the at least one maltitol-internalizing.and / or maltitol-mctabolizing, and / or maltitol-supportcd bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the proportion and / or concentration can be increased by at least 1%, at least 2%. at least 3%, at least 4%, at least 5%, at least 10%, at least 20%, at least 30%. at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0258] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing. and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the synbiotic composition increases the production of y-aminobutyric acid (GABA) by the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. As a non-limiting example, the production of y-aminobutyric acid (GABA) can be increased by at least 1%, at least 2%, at least 3%. at least 4%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%. at least 60%, at least 70%, at least 80%. at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%. or more.

[0259] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the sy nbiotic composition increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. As a nonlimiting example, the concentration of y-aminobutyric acid (GABA) can be increased by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%. at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0260] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject. In some embodiments of any of the aspects, the increased production rate and / or concentration of y- aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, orfcccs of the mammalian subject reduces stress and / or anxiety in the subject. In some embodiments of any of the aspects, die increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacteroides or the at least one bacterium of the genus Bifidobacterium in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder.

[0261] In some embodiments of any of the aspects, the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), Neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

[0262] In some embodiments of any of the aspects, treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder. In some embodiments of any of the aspects, at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of selfharm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility’, quality’ of life score, and combinations thereof.

[0263] In some embodiments of any of the aspects, the synbiotic composition further comprises at least one excipient (e.g., 1, 2. 3, 4, 5, 6, 7, 8, 9, 10, or more excipients). In some embodiments of any of the aspects, the at least one excipient is selected from the group consisting of encapsulation materials (e.g., chitosan, wax, and gelatin), solubilizers (e.g., TWEEN 80 or SPAN 60), bulking agents (e.g., maltodextrin or microcrystalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g., ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof.

[0264] In some embodiments of any of the aspects, the synbiotic composition further comprises at least one additional prebiotic (e.g., 1, 2. 3, 4, 5, 6, 7. 8. 9, 10. or more prebiotics in addition to maltitol). In some embodiments of any of the aspects, the at least one additional prebiotic is selected from the group consisting of amino acid (e.g.. arginine, glutarate, and ornithine), biotin,fructooligosaccharidc, galactooligosaccharidc, hemi cellulose (e.g., arabinoxylan. xylan, xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, gum (e.g., guar gum, gum arabic and carrageenan), oligofructose, oligodextrose, tagatose, resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide, pectin (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fiber (e.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccharide, and poly amine (e.g., spermidine, putrescine).

[0265] In some embodiments of any of the aspects, the synbiotic composition is formulated for delivery to the gut of a mammalian subject. In some embodiments of any of the aspects, the synbiotic composition is in the form of a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

[0266] The synbiotic compositions described herein can be taken by a subject daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks, 3 weeks, 4 weeks. 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or more, for example, up to lifetime use.Nutritional Supplements

[0267] In multiple aspects, described herein are nutritional supplements. In one aspect, described herein is a nutritional supplement comprising a prebiotic composition as described herein and / or a synbiotic composition as described herein.

[0268] In one aspect, described herein is a nutritional supplement comprising a prebiotic composition as described herein. In some embodiments of any of the aspects, the prebiotic composition is at a concentration of at least 1% to at most 70% in the nutritional supplement. As non-limiting examples, the prebiotic composition is at a concentration of at least 1%, at least 5%. at least 10%, at least 20%, at least 30%, at least 40%, at least 50%. at least 60%, or at least 70% in the nutritional supplement.

[0269] In one aspect, described herein is a nutritional supplement comprising a synbiotic composition as described herein. In some embodiments of any of the aspects, the synbiotic composition is at a concentration of at least 1% to at most 70% in the nutritional supplement. As nonlimiting examples, the synbiotic composition is at a concentration of at least 1%. at least 5%. at least 10%, at least 20%, at least 30%. at least 40%, at least 50%. at least 60%, or at least 70% in the nutritional supplement.

[0270] In some embodiments of any of the aspects, the nutritional supplement is formulated for delivery to the gut of a mammalian subject. In some embodiments of any of tire aspects, the nutritional supplement is in the form of a probiotic, a prebiotic, a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

[0271] The nutritional supplements described herein can be taken by a subject daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, 1 year, 2 years. 3 years. 4 years. 5 years. 10 years, or more, for example, up to lifetime use.Food Compositions

[0272] In multiple aspects, described herein are food compositions. In one aspect, described herein is a food composition comprising a prebiotic composition as described herein. In some embodiments of any of the aspects, the prebiotic composition is at a concentration of at least 1% to at most 70% in the food composition. As non-limiting examples, the prebiotic composition is at a concentration of at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%. at least 60%, or at least 70% in the food composition.

[0273] In one aspect, described herein is a food composition comprising a symbiotic composition as described herein. In some embodiments of any of the aspects, the symbiotic composition is at a concentration of at least 1% to at most 70% in the food composition. As non-limiting examples, the symbiotic composition is at a concentration of at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% in the food composition.

[0274] In some embodiments of any of the aspects, the food composition is selected from the group consisting of milk, plant-based dairy alternatives (e.g., oat milk, almond milk, coconut milk, soy milk, pea milk, etc.), fermented milk, yogurt, yogurt beverages, protein shakes, fruit juice (e.g., apple juice, orange juice, grapefruit juice, grape juice, etc.), granola bars, meal replacement bars, protein bars, fruit bars, chewing gum, confectionary (e g., soft chew candy, gummy candy, hard candy, etc.), frozen confections, breakfast cereals, pastas, bread products (e.g.. loaves, buns, croutons, etc.), condiments and relishes (e.g., ketchup, relish, etc.), alcoholic beverages (e.g.. canned cocktail, alcoholic cider, etc.), frosting, gelatin and pudding, cough drops, jams and jellies, syrups, and sauces (e.g.. tomato sauce, barbeque sauce, etc.).

[0275] In some embodiments of any of the aspects, the food composition is selected from the group consisting of milk, yogurt, plant-based dairy' alternatives (e.g., oat milk, almond milk, coconut milk, soy milk, pea milk, etc.), soft drinks (e.g., soda, carbonated water, etc.), fermented milk, protein shakes, fruit juice (e.g.. apple juice, orange juice, grapefruit juice, grape juice, etc.), non-dairy fermented beverages (e.g., kombucha. etc.), vegetable juices (e.g. carrot juice, tomato juice, etc ), alcoholic beverages (e.g.. canned cocktail, alcoholic cider, etc ), sauces (e.g., gravy, tomato sauce, barbeque sauce, etc.), broth and stock (e.g., chicken stock, beef broth, vegetable broth, etc.), syrups, tea beverages (e.g., tea-based powder, milk tea, etc.), coffee beverages (e.g.. cold brew, latte, iced coffee), yogurt beverages, or cereal-based beverages (e.g., rice milk, beer, barley tea, etc.).

[0276] In some embodiments of any of die aspects, the food composition is selected from the group consisting of granola bars, meal replacement bars, protein bars, fruit bars, breakfast cereals, pastas, bread products (e.g., loaves, buns, croutons, etc.), condiments and relishes (e.g., ketchup, relish, etc.), frosting, gelatin and pudding, cough drops, or jams and jellies.

[0277] In some embodiments of any of the aspects, the food composition is selected from the group of food concentrates consisting of bouillon concentrate, soup concentrate, or gravy' concentrate.

[0278] In some embodiments of any of the aspects, the food composition is a confectionary selected from the group consisting of a chocolate composition, a chocolate analogue composition, chewing gum, soft chew candy, gummy candy, or hard candy.

[0279] In some embodiments of any of the aspects, the food composition is a frozen confection (e.g., ice cream, sorbet, sherbet, frozen yogurt or water ice), is a frozen confection product comprising a frozen composition and a chocolate composition or a chocolate analogue composition wherein the chocolate composition or a chocolate analogue composition is in the form of a coating on the frozen composition and / or inclusions located within the frozen composition and / or a ripple or swirl of sauce.

[0280] In some embodiments of any of the aspects, the food composition is a frozen confection (e.g.. ice cream, sorbet, sherbet, frozen yogurt or water ice), or is a frozen confection product comprising a frozen composition and a chocolate composition or a chocolate analogue composition. Ice cream typically contains fat, non-fat milk solids (of which about one third is milk protein and about half is lactose) and sugars, together with other minor ingredients such as stabilizers, emulsifiers, colors, and flavorings. As used herein “ice cream” encompasses both dairy -based frozen confections and vegetable-based frozen confections (e.g., vegan analogues of traditional dairy' ice cream). Water ice typically contains sugars together with stabilizers, colors, and flavorings.

[0281] In some embodiments of any of tire aspects, the food composition is a frozen confection wherein the chocolate composition or a chocolate analogue composition is in the form of a coating on the frozen composition and / or inclusions located within the frozen composition and / or a ripple or swirl of sauce. In some embodiments of any of the aspects, the food composition is a chocolate composition or a chocolate analogue composition.

[0282] In one aspect described herein is a use of maltitol for replacing sugar in a food composition. In some embodiments of any of the aspects, 1% to 100% of the sugar in the food composition is replaced with maltitol. In some embodiments of any of the aspects, at least 1%, at least 2%, at least 3%. at least 4%, at least 5%, at least 6%, at least 7%, at least 8%. at least 9%, at least 10%, at least 11%, at least 12%. at least 13%, at least 14%, at least 15%, at least 16%, at least 17%. at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%. at least 25%, at least 26%, at least 27%. at least 28%, at least 29%, at least 30%, at least 31%, at least 32%. at least 33%, at least 34%, at least 35%, at least 36%. at least 37%, at least 38%, at least 39%. at least 40%, at least 41%, at least 42%. at least 43%, at least 44%. at least 45%, at least 46%, at least 47%. at least 48%, atleast 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%. at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%. or 100% of the sugar in the food composition is replaced with maltitol.

[0283] Further non-limiting details applicable to such food compositions can be found in US patent publication US 20090285947 Al, and International patent publications WO 2019115731 Al, WO 2022048873 Al, WO 2022048952 Al, WO 2014079964 Al, and WO 2015055456 Al, the contents of each of which are incorporated herein by reference in their entireties.

[0284] The food compositions described herein can be taken by a subject daily, twice daily, three times daily or four or more times daily over a period of 1 week. 2 weeks, 3 weeks. 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or more, for example, up to lifetime use.Medical Foods

[0285] In multiple aspects, described herein are medical foods. In one aspect, described herein is a medical food formulated to provide a daily dosage of an effective amount of maltitol. In one aspect, described herein is a medical food formulated to provide a daily dosage of an effective amount of maltitol and a daily dosage of at least one bacterial species.

[0286] In one aspect, described herein is a medical food for the improvement of mood in a mammalian subject in need thereof. In one aspect, described herein is a medical food for the promotion of relaxation in a mammalian subject in need thereof. In one aspect, described herein is a medical food for the promotion of a calming mood state in a mammalian subject in need thereof. In one aspect, described herein is a medical food for the treatment of depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof.

[0287] In some embodiments of any of the aspects, the medical food comprises an effective amount of maltitol. In some embodiments of any of the aspects, the medical food comprises an effective amount of maltitol and at least one bacterial species. In some embodiments of any of the aspects, the medical food is formulated to provide a daily dosage of maltitol. In some embodiments of any of the aspects, the medical food is formulated to provide a daily dosage of maltitol and a daily dosage of at least one bacterial species.

[0288] In some embodiments of any of tire aspects, the daily dosage of maltitol is in in the effective amount of 0.5g to 25g. In some embodiments of any of the aspects, the daily dosage of maltitol is inin the effective amount of 0.5g to 12g. In some embodiments of any of the aspects, the daily dosage of maltitol is in in the effective amount of about 0.5g, about 0.6g, about 0.7g, about 0.8g, about 0.9g, about 1g, about 1.1g, about 1.2g, about 1.3g, about 1.4g, about 1.5g, about 1.6g, about 1.7g, aboutI.8g, about 1.9g, about 2g, about 2.1g, about 2.2g, about 2.3g, about 2.4g, about 2.5g, about 2.6g, about 2.7g, about 2.8g. about 2.9g, about 3g, about 3.1g, about 3.2g, about 3.3g. about 3.4g, about 3.5g, about 3.6g, about 3.7g, about 3.8g, about 3.9g, about 4g, about 4.1g, about 4.2g, about 4.3g, about 4.4g, about 4.5g. about 4.6g, about 4.7g, about 4.8g, about 4.9g, about 5g, about 5.1g, about 5.2g, about 5.3g, about 5.4g, about 5.5g, about 5.6g, about 5.7g, about 5.8g. about 5.9g, about 6g, about 6.1g, about 6.2g. about 6.3g, about 6.4g, about 6.5g, about 6.6g, about 6.7g. about 6.8g, about 6.9g, about 7g, about 7.1g. about 7.2g, about 7.3g. about 7.4g, about 7.5g, about 7.6g, about 7.7g, about 7.8g, about 7.9g. about 8g. about 8.1g, about 8.2g. about 8.3g, about 8.4g, about 8.5g, about 8.6g, about 8.7g, about 8.8g, about 8.9g, about 9g. about 9.1g, about 9.2g, about 9.3g. about 9.4g, about 9.5g, about 9.6g. about 9.7g, about 9.8g, about 9.9g, about 10g, about 10.1g, about 10.2g, about 10.3g, about 10.4g, about 10.5g, about 10.6g, about 10.7g, about 10.8g, about 10.9g, about 11g. aboutI I.1g. about 11.2g. about 11.3g. about 11.4g, about 11.5g, about 11.6g, about 11.7g. about 11.8g. about 11.9g, about 12g. about 12.1g, about 12.2g, about 12.3g, about 12.4g, about 12.5g. about 12.6g. about 12.7g, about 12.8g. about 12.9g, about 13g, about 13.1 g, about 13.2g, about 13.3g. about 13.4g, about 13.5g, about 13.6g. about 13.7g, about 13.8g, about 13.9g, about 14g, about 14.1g. about 14.2g, about 14.3g, about 14.4g. about 14.5g, about 14.6g, about 14.7g, about 14.8g, about 14.9g. about 15g, about 15.1g, about 15.2g. about 15.3g, about 15.4g, about 15.5g, about 15.6g, about 15.7g. about 15.8g. about 15.9g, about 16g, about 16.1g, about 16.2g, about 16.3g. about 16.4g, about 16.5g, about 16.6g. about 16.7g, about 16.8g, about 16.9g, about 17g, about 17.1g. about 17.2g, about 17.3g, about 17.4g. about 17.5g, about 17.6g, about 17.7g, about 17.8g, about 17.9g, about 18g, about 18.1g, about 18.2g, about 18.3g, about 18.4g, about 18.5g, about 18.6g, about 18.7g, about 18.8g, about 18.9g, about 19g, about 19.1g, about 19.2g, about 19.3g, about 19.4g, about 19.5g, about 19.6g, about 19.7g, about 19.8g, about 19.9g, about 20g, about 20.1g, about 20.2g, about 20.3g, about 20.4g, about 20.5g, about 20.6g. about 20.7g, about 20.8g, about 20.9g, about 21g, about 21.1g. about 21.2g, about 21.3g, about 21.4g. about 21.5g, about 21.6g, about 21.7g, about 21.8g, about 21.9g, about 22g, about 22.1g, about 22.2g. about 22.3g, about 22.4g, about 22.5g, about 22.6g, about 22.7g, about 22.8g, about 22.9g, about 23g, about 23.1g, about 23.2g, about 23.3g, about 23.4g, about 23.5g, about 23.6g, about 23.7g, about 23.8g, about 23.9g, about 24g, about 24.1g. about 24.2g, about 24.3g, about 24.4g, about 24.5g, about 24.6g, about 24.7g, about 24.8g, about 24.9g, or about 25g, e.g., per serving size of the medical food.

[0289] In some embodiments of any of the aspects, the daily dosage of the at least one bacterial species is 101CFU / g to 1013CFU / g. In some embodiments of any of the aspects, the daily dosage of the at least one bacterial species is about 101CFU / g. about 102CFU / g, about 103CFU / g, about 104CFU / g, about 105CFU / g, about 106CFU / g, about 107CFU / g, about 108CFU / g, about 109CFU / g, about IO10CFU / g, about 1011CFU / g, about 1012CFU / g, about 1013CFU / g, or more.

[0290] In some embodiments of any of the aspects, the daily dosage of maltitol and / or tire at least one bacterial species is based on a serving size of about 0.8g to 125 g of said medical food. In some embodiments of any of the aspects, the serving size of the medical food is about 0.8g, about 0.9g, about 1g, about 1.1g, about 1.2g, about 1.3g, about 1.4g, about 1.5g, about 1.6g, about 1.7g, about 1.8g, about 1.9g, about 2g, about 2.1g, about 2.2g. about 2.3g, about 2.4g, about 2.5g, about 2.6g, about 2.7g, about 2.8g. about 2.9g, about 3g, about 3.1g. about 3.2g, about 3.3g. about 3.4g, about 3.5g, about 3.6g, about 3.7g, about 3.8g, about 3.9g. about 4g, about 4.1g, about 4.2g, about 4.3g, about 4.4g, about 4.5g. about 4.6g, about 4.7g, about 4.8g, about 4.9g, about 5g, about 6g, about 7g, about 8g, about 9g, about 10g, about 15g. about 20g, about 25g, about 30g, about 35g. about 40g, about 45g, about 50g, about 55g. about 60g. about 65g, about 70g, about 75g. about 80g, about 85g, about 90g, about 95g, about 100g, about 105g, about 110g, about 115g, about 120g, or about 125g.

[0291] In some embodiments of any of the aspects, the medical food is taken up to three times a day. for example. 1. 2. or 3 times a day. In some embodiments of any of the aspects, the serving size is such that that amount is in one daily serving, or in. for example, two servings, taken at breakfast and dinner, or in three servings, taken with each of breakfast, lunch and dinner, etc. The medical foods described herein can be taken by a subject daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, or more, for example, up to lifetime use.Pharmaceutical Compositions

[0292] In multiple aspects, described herein are pharmaceutical compositions. In one aspect, described herein is a pharmaceutical composition comprising a prebiotic composition as described herein and a pharmaceutically acceptable carrier. In some embodiments of any of the aspects, the prebiotic composition is at a concentration of at least 1% to at most 70% in the pharmaceutical composition. As non-limiting examples, the prebiotic composition is at a concentration of at least 1%. at least 5%, at least 10%, at least 20%. at least 30%, at least 40%. at least 50%, at least 60%, or at least 70% in the pharmaceutical composition.

[0293] In one aspect, described herein is a pharmaceutical composition comprising a symbiotic composition as described herein and a pharmaceutically acceptable carrier. In some embodiments of any? of the aspects, the symbiotic composition is at a concentration of at least 1% to at most 70% in the pharmaceutical composition. As non-limiting examples, the synbiotic composition is at a concentration of at least 1%, at least 5%, at least 10%, at least 20%. at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% in the pharmaceutical composition.

[0294] In some embodiments, the active ingredients of the pharmaceutical composition comprise a prebiotic composition as described herein (e.g., an effective amount of maltitol) or a symbiotic composition as described herein (e.g.. an effective amount of maltitol and at least one bacterial species, e.g., selected from Table 5, Table 6, Table 11 (e.g., “increased” column), Table 12, or Table 13). In some embodiments, the active ingredients of the pharmaceutical composition consist essentially of the prebiotic or symbiotic composition as described herein. In some embodiments, the active ingredients of the pharmacal composition consist of the prebiotic or synbiotic composition as described herein.

[0295] Pharmaceutically acceptable carriers and diluents include saline, aqueous buffer solutions, solvents and / or dispersion media. The use of such carriers and diluents is well known in the art. Some non-limiting examples of materials which can serve as pharmaceutically-acceptable carriers include:(I) sugars, such as lactose, glucose and sucrose; (2) starches, such as com starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, microcrystalline cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) lubricating agents, such as magnesium stearate, sodium lauryl sulfate and talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; (10) glycols, such as propylene glycol;(I I) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol (PEG); (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) pH buffered solutions; (21) polyesters, polycarbonates and / or polyanhydrides; (22) bulking agents, such as polypeptides and amino acids; (23) serum component, such as scram albumin, HDL and LDL; (24) C2-C12 alcohols; and (25) other non-toxic compatible substances employed in pharmaceutical formulations. Wetting agents, coloring agents, release agents, coating agents, sweetening agents, flavoring agents, perfuming agents, preservative and antioxidants can also be present in the formulation. The terms such as "excipient", "carrier", "pharmaceutically acceptable carrier" or the like are used interchangeably herein. In some embodiments, the carrier inhibits the degradation of the active agent, e.g., the prebiotic or synbiotic composition as described herein.

[0296] To the extent that additional sugar alcohols, polyols or other carriers, excipients or diluents are included, it is preferred that they not inhibit the growth or metabolic function of maltitol- internalizing, maltitol metabolizing, maltitol-supported, and / or GABA-producing bacteria and / or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject. Similarly, to the extent that additional sugar alcohols, polyols or other carriers, excipients or diluents are included, it is preferred that they not promote the growth or metabolic function of bacteria of the family Enterobacteriaceae.

[0297] Pharmaceutical compositions comprising the prcbiotic or symbiotic composition as described herein can be formulated to be suitable for oral administration, for example as discrete dosage forms, such as, but not limited to, tablets (including without limitation scored or coated tablets), pills, caplets, capsules, chewable tablets, powder packets, cachets, troches, wafers, aerosol sprays, or liquids, such as but not limited to, syrups, elixirs, solutions or suspensions in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil emulsion. Such compositions contain a predetermined amount of the pharmaceutically acceptable salt of the disclosed compounds, and may be prepared by methods of pharmacy well known to those skilled in the art. See generally, Remington: The Science and Practice of Pharmacy, 21st Ed.. Lippincott, Williams, and Wilkins. Philadelphia PA. (2005).

[0298] In some embodiments of any of the aspects, the pharmaceutical composition is formulated for delivery to the gut of a mammalian subject. In some embodiments of any of the aspects, the pharmaceutical composition is in the form of a probiotic, a prebiotic, a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

[0299] With respect to dosage, duration, and frequency of treatment, it is typical for skilled clinicians to monitor subjects in order to determine when the treatment is providing therapeutic benefit, and to determine whether to increase or decrease dosage, increase or decrease administration frequency, discontinue treatment, resume treatment, or make other alterations to the treatment regimen.

[0300] In certain embodiments, an effective dose of a pharmaceutical composition as described herein can be administered to a patient once. In certain embodiments, an effective dose of a pharmaceutical composition as described herein can be administered to a patient repeatedly.

[0301] The dosing schedule can vary from once a week to daily depending on a number of clinical factors, such as the subject's sensitivity to the pharmaceutical composition ingredients. The desired dose or amount can be administered at one time or divided into subdoses, e.g., 2-4 subdoses and administered over a period of time, e.g., at appropriate intervals through the day or other appropriate schedule. In some embodiments, administration can be one or more doses and / or treatments daily over a period of weeks or months. Examples of dosing and / or treatment schedules are administration daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, 1 year. 2 years. 3 years. 4 years. 5 years. 10 years, or more, for example, up to lifetime use. A pharmaceutical composition as described herein can be administered over a period of time, such as over a 5 minute, 10 minute. 15 minute, 20 minute, or 25 minute period. Where maltitol has been found to promote the selective expansion or increase in abundance of certain beneficial bacterial species in the mammalian gut, the beneficial effects can be promoted or maintained by repeated intake or administration ofmaltitol or maltitol-containing formulations or compositions in effective amounts as described herein - that is, in certain embodiments, selective pressure to maintain the abundance or proportion of beneficial bacterial species (and / or to suppress the abundance or proportion of deleterious, pathogenic or dysbiotic species) in the gut can be provided by the intake or dosing regimen used.

[0302] In some embodiments, after an initial treatment regimen, the treatments can be administered on a less frequent basis. For example, after treatment biweekly for three months, treatment can be repeated once per month, for six months or a year or longer.Methods

[0303] In multiple aspects, described herein are methods of using the compositions described herein, including but not limited to prebiotic compositions, synbiotic compositions, nutritional supplements, food compositions, medical foods, and / or pharmaceutical compositions.

[0304] In one aspect, described herein is a method of improving mood in a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0305] In one aspect, described herein is a method of promoting relaxation and / or promoting a calming mood state in a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0306] In one aspect, described herein is a method of reducing stress or anxiety in a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0307] In one aspect, described herein is a method of increasing the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0308] In one aspect, described herein is a method of increasing the production rate of y- aminobutyric acid (GABA) by at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, and / or increasing the concentration of y-aminobulyric acid (GABA) in tire gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a mammalian subject, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein.

[0309] In one aspect, described herein is a method of treating depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, the method comprising administering an effective amount of a prebiotic composition as described herein, a synbiotic composition as described herein, a nutritional supplement as described herein, a food composition as described herein, a medical food as described herein, or a pharmaceutical composition as described herein. It is contemplated that selection for maltitol-metabolizing gut bacteria or promotion of metabolite production by maltitol-metabolizing bacteria, e.g., through administering or adding to or increasing the amount of maltitol in the diet of a subject, whether in the form or a prebiotic composition, symbiotic composition, nutritional supplement, food composition, medical food, or pharmaceutical composition as described herein, can promote unproved mood, relaxation, a calming mood state, reduced stress or anxiety or other beneficial effect on mental health through a mechanism other than, or in addition to promotion of GABA production.

[0310] In some embodiments of any of the aspects, the mammalian subject is a human. In some embodiments of any of the aspects, the administering is to the gut of the subject.

[0311] In some embodiments of any of the aspects, improving mood in the mammalian subject, promoting relaxation and / or promoting a calming mood state in the mammalian subject, and / or reducing stress and / or anxiety in the mammalian subject is measured by a test selected from the group consisting of the Hopkins Symptom Checklist-25, Hamilton Depression Rating Scale, the Beck Depression Inventory, Positive and Negative Affect Schedule, Profile of Mood states (POMS) Questionnaire, a friendliness score, General Anxiety Disorder Questionnaire-7 (GAD-7), Visual Analog Mood Scale. VAS / Likert Scale. Perceived Stress Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Center for Epidemiologic Studies Depression Scale. Geriatric Depression Scale, Montgomery -Asberg Depression Rating Scale, Cohen’s Perceived Stress Scale, Holmes and Rahe Stress Scale, World Health Organization Quality of Life, Short Form Health Survey (SF-36), and EuroQol five dimensions questionnaire, or a combination thereof.

[0312] In some embodiments of any of the aspects, mood is improved in the subject by at least 5%. As non-limiting examples, mood is improved in the subject by at least 1%, at least 2%. at least 3%, atleast 4%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, or more as measured by, e.g., a test or scale as described herein above.

[0313] In some embodiments of any of the aspects, relaxation is promoted in the subject by at least 5%. As non-limiting examples, relaxation is promoted in the subject by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%. at least 10%, at least 20%, at least 30%, at least 40%, at least 50%. at least 60%, at least 70%, at least 80%. at least 90%, at least 100%, or more as measured by, e.g., a test or scale as described herein above.

[0314] In some embodiments of any of the aspects, a calming mood state is promoted in the subject by at least 5%. As non-limiting examples, a calming mood state is promoted in the subject by at least 1%. at least 2%. at least 3%, at least 4%, at least 5%, at least 10%, at least 20%. at least 30%, at least 40%, at least 50%. at least 60%, at least 70%. at least 80%, at least 90%, at least 100%, or more as measured by, e.g., a test or scale as described herein above.

[0315] In some embodiments of any of the aspects, stress and / or anxiety is reduced in the subject by at least 5%. As non-limiting examples, stress and / or anxiety is reduced in the subject by at least 1%, at least 2%, at least 3%. at least 4%, at least 5%, at least 10%. at least 20%, at least 30%, at least 40%. at least 50%, at least 60%, at least 70%, at least 80%. at least 90%, at least 100%, or more as measured by, e g., a test or scale as described herein above.

[0316] In some embodiments of any of the aspects, the salivary cortisol awakening response is reduced in the subject by at least 5%. The salivary cortisol awakening response is the increase in salivary cortisol levels that happens after waking up. The magnitude of the salivary cortisol awakening response can be an indicator of stress levels. A less pronounced or attenuated cortisol awakening response, meaning a smaller increase in salivary cortisol from pre-awakening baseline to shortly after waking compared to a control (e.g.. a subject not administered a composition described herein; e.g., the subject prior to being administered a composition described herein; e.g., a subject administered a placebo), can be indicative of decreased stress levels. Conversely, a more robust or exaggerated cortisol awakening response compared to a control can be associated with increased stress. The salivary cortisol awakening response can be measured by taking saliva samples at multiple time points after waking (e.g., 0 minutes, 30 minutes, 45 minutes, and / or 60 minutes) and determining the level of cortisol in such saliva samples. Specific measurements of the salivary cortisol awakening response include Area Under the Curve (of the salivary cortisol levels at multiple timepoints), the Cmax (peak concentration of salivary cortisol), and the Tmax (time to peak concentration of salivary cortisol). As non-limiting examples, the salivary cortisol awakening response (e.g., area under the curve, Cmax, and / or Tmax) is reduced in the subject by at least 1%. at least 2%, at least 3%, at least 4%, at least 5%, at least 10%. at least 20%, at least 30%, at least 40%. at least 50%, at least 60%, atleast 70%, at least 80%, at least 90%, at least 100%, or more as measured by, e.g., a test or scale as described herein above.

[0317] In some embodiments of any of the aspects, cortisol levels in blood and / or saliva are reduced in the subject by at least 5% compared to a control. Blood and salivary cortisol are established biomarkers for assessing physiological stress. Cortisol, a glucocorticoid hormone produced by the adrenal glands, is a key regulator of the body's response to stress. Measurement of cortisol concentrations in blood allows for the quantification of circulating cortisol, both bioavailable and protein-bound cortisol. Measurement of cortisol concentrations in saliva allows for the quantification of bioavailable cortisol. Specific measurements of cortisol levels include basal cortisol levels (cortisol levels at a specific time point, e.g., in the morning or evening), diurnal cortisol rhythm (the fluctuation of cortisol levels throughout the day), and cortisol response to stimuli (e.g., stress tests). As nonlimiting examples, basal cortisol levels, diurnal cortisol rhythm, and / or cortisol response to stimuli are reduced in the subject by at least 1%, at least 2%, at least 3%. at least 4%. at least 5%, at least 10%. at least 20%, at least 30%, at least 40%, at least 50%. at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to a control, as measured by, e.g., a test or scale as described herein above.

[0318] In some embodiments of any of tire aspects, at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium internalizes and / or metabolizes and / or is supported by maltitol from the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) in the gut of the mammalian subject.

[0319] In some embodiments of any of the aspects, the internalization and / or metabolization by or die support of die at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of die genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) increases the relative and / or absolute abundance of the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the relative and / or absolute abundance can be increased by at least 1%. at least 2%, at least 3%, at least 4%. at least 5%. at least 10%, at least 20%, at least 30%. at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%. at least 500%. at least 600%. at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0320] In some embodiments of any of the aspects, the increase of the relative and / or absolute abundance of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium is determined by: (i) quantifying the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject before ingestion of the composition; (ii) quantifying the at least one maltitol-intemalizing. and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject after ingestion of the composition; (iii) and determining the relative and / or absolute abundance of the at least one maltitol-intemalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium from the data from (ii) compared to the data from (i).

[0321] In some embodiments of any of the aspects, quantification of (i) and / or (ii) comprises nucleic acid sequencing. In some embodiments of any of the aspects, the nucleic acid sequencing comprises 16S metagenomic sequencing, shotgun metagenomic sequencing, and / or amplification and sequencing of the 16S gene by polymerase chain reaction and sequencing. In some embodiments of any of the aspects, quantification of (i) and / or (ii) comprises non-sequencing-based methods (e.g., culture-based methods).

[0322] In some embodiments of any of the aspects, the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifaciens, B. caccae, B. caecicola, B. caecigallinarum, B. cellulosilyticus, B. cellulosolvens, B. clarus, B. coagulans, B. coprocola, B. coprophilus, B. coprosuis, B. dorei, B. eggerthii, B. faecichinchillae, B. faecis, B. finegoldii, B. fluxus, B. fragilis, B. galacturonicus, B. gallinaceum, B. gallinarum, B. goldsteinii, B. graminisolvens, B. helcogene, B. intestinalis, B. luti, B. massiliensis, B. nordii, B. oleiciple us, B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifaciens, B. putredinis, B. pyogenes, B. reticulotermitis, B. rodentium, B. salanitronis. B. salyersiae, B. sartorii, B. stercoris, B. thelaiolaomicron, B. uniformis. B. vulgalus, and B. xylanisolvens.

[0323] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) increases the growth rate and / or metabolic activity of the at least one maltitol-intemalizing, and / or maltitol-metabolizing,and / or maltitol-supportcd bacterial species or the at least one bacterium of the genus Bacteroides or die at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a non-limiting example, the growth rate and / or metabolic activity can be increased by at least 1%, at least 2%, at least 3%. at least 4%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%. at least 800%. at least 900%, at least 1000%, or more.

[0324] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing. and / or maltitol- supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) increases the proportion and / or concentration of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. As a nonlimiting example, the proportion and / or concentration can be increased by at least 1 %, at least 2%, at least 3%, at least 4%. at least 5%, at least 10%, at least 20%, at least 30%. at least 40%, at least 50%, at least 60%. at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0325] In some embodiments of any of the aspects, the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the composition (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) increases the production of y- aminobutyric acid (GABA) by the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. As a non-limiting example, the production of y-a inobutyric acid (GABA) can be increased by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 20%. at least 30%, at least 40%, at least 50%, at least 60%. at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%. at least 900%. at least 1000%. or more.

[0326] In some embodiments of any of the aspects, the internalization and / or metabolization by or die support of die at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol in the composition (e g., a prebiotic composition, symbiotic composition, nutritional supplement, food composition, a medical food, and / or pharmaceutical composition as described herein) increases the concentration of y- aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. As a non-limiting example, the concentration of y- aminobutvric acid (GABA) can be increased by at least 1%, at least 2%, at least 3%, at least 4%. at least 5%, at least 10%. at least 20%, at least 30%, at least 40%. at least 50%, at least 60%, at least 70%, at least 80%. at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more.

[0327] In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject. In some embodiments of any of the aspects, the increased production rate and / or concentration of y- aminobutyric acid (GABA) in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject. In some embodiments of any of the aspects, the increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacteroides or the at least one bacterium of the genus Bifidobacterium in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder.

[0328] In some embodiments of any of the aspects, the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), Neurodegenerative amyloid disorders (Parkinson's. Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.1003291 In some embodiments of any of the aspects, treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder. In someembodiments of any of the aspects, at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of selfharm, restlessness, low sex drive, lack of focus, seizures, memory' loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

[0330] In some embodiments of any of the aspects, the method further comprises administering at least one mood-improving therapeutic to the subject. In some embodiments of any of the aspects, the method further comprises administering at least one anti-depression, anti-anxiety, and / or anti-stress therapeutic to the subject.|003311 In some embodiments of any of the aspects, the method further comprises identifying a subject in need of treatment by determining whether the subject would benefit from an increase in endogenous GABA and / or GABA-producing bacteria by measuring an initial amount of GABA in the subject's stool. In some embodiments of any of the aspects, the initial amount of endogenous GABA in the subject's stool is below about 300 pg per gram (pg / g), about 200 pg / g. about 100 pg / g, about 50 pg / g, about 20 pg / g, or about 10 pg / g of wet or dry stool.

[0332] In some embodiments of any of the aspects, the amount of GABA in the subject's stool is increased relative to the initial amount after administering the maltitol formulation. In some embodiments of any of the aspects, the amount of GABA in the subject's stool is increased by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. As a non-limiting example, the relative and / or absolute abundance can be increased by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more, relative to the initial amount after administering the maltitol formulation.

[0333] In some embodiments of any of the aspects, the method further comprises identifying a subject in need of treatment by determining whether the subject would benefit from an increase in endogenous GABA by measuring an initial amount of GABA-producing bacteria in the subject's stool. In some embodiments of any of the aspects, the initial amount of GABA-producing bacteria in the subject's stool is less than about 50%, about 40%, about 30%. about 20%, about 10%, about 5%, or about 1% of total bacteria as measured by 16S sequence mapping.

[0334] In some embodiments of any of the aspects, the amount of GABA-producing bacteria in the subject's stool is increased relative to the initial amount after administering the maltitol formulation. In some embodiments of any of the aspects, the amount of GABA-producing bacteria in the subject's stool is increased by at least 1%, at least 2%, at least 3%, at least 4%. at least 5%, at least 10%, at least20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, or more, relative to the initial amount after administering the maltitol formulation.

[0335] In some embodiments of any of the aspects, the GABA-producing bacteria comprise at least one of the maltitol-increased bacteria as described further herein. In some embodiments of any of the aspects, the GABA-producing bacteria comprise at least one maltitol-internalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species as described further herein. In some embodiments of any of the aspects, the GABA-producing bacteria are selected from Table 5, Table 6, Table 11 (e.g., "increased” column), Table 12, or Table 13. In some embodiments of any of the aspects, the GABA-producing bacteria encode or express a protein or protein complex that internalizes and / or metabolizes maltitol selected from Table 9 or Table 10. In some embodiments of any of tire aspects, the GABA-producing bacteria comprise at least one bacterium of the genus Bacteroides, non-limiting examples of which are provided herein.

[0336] In some embodiments, the methods described herein relate to treating a subject having or diagnosed as having a mental disease or disorder with a composition as described herein (e g., a prebiotic composition, symbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein). Subjects having a mental disease or disorder can be identified by a physician using current methods of diagnosing a mental disease or disorder.

[0337] The compositions described herein can be administered to a subject having or diagnosed as having a mental disease or disorder. In some embodiments, the methods described herein comprise administering an effective amount of compositions described herein to a subject in order to alleviate a symptom of a mental disease or disorder. As used herein, "alleviating a symptom of a mental disease or disorder " is ameliorating any condition or sy mptom associated with the mental disease or disorder. As compared with an equivalent untreated control, such reduction is by at least 5%, 10%, 20%, 40%, 50%, 60%, 80%, 90%, 95%, 99% or more as measured by any standard technique.

[0338] As described herein, levels of GABA and / or GABA-producing bacteria can be decreased in a mental disease or disorder and / or in subjects with a mental disease or disorder. Accordingly, in one aspect of any of the embodiments, described herein is a method of treating a mental disease or disorder in a subject in need thereof, the method comprising administering a composition as described herein (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein) to a subject determined to have a level of GABA and / or GABA-producing bacteria that is decreased relative to a reference. The level of GABA can be determined in a sample from the gut of the subject or from a blood plasma or serum, cerebrospinal fluid, breast milk, or fecal sample from the subject. The level ofGABA-producing bacteria can be determined in a sample from the gut of the subject or from a fecal sample from the subject. In one aspect of any of the embodiments, described herein is a method of treating a mental disease or disorder in a subject in need thereof, the method comprising: a) determining the level of GABA and / or GABA-producing bacteria in a sample obtained from a subject; and b) administering a composition as described herein (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein) to the subject if the level of GABA and / or GABA- producing bacteria is decreased relative to a reference.

[0339] In some embodiments of any of the aspects, the method comprises administering a composition as described herein (e.g.. a prebiotic composition, synbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein) to a subject previously determined to have a level of GABA and / or GABA-producing bacteria that is decreased relative to a reference. In some embodiments of any of the aspects, described herein is a method of treating a mental disease or disorder in a subject in need thereof, the method comprising: a) first determining the level of GABA and / or GABA-producing bacteria in a sample obtained from a subject; and b) then administering a composition as described herein (e.g.. a prebiotic composition, synbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein) to the subject if the level of GABA and / or GABA- producing bacteria is decreased relative to a reference.

[0340] In one aspect of any of the embodiments, described herein is a method of treating a mental disease or disorder in a subject in need thereof, the method comprising: a) determining if the subject has a decreased level of GABA and / or GABA-producing bacteria; and b) administering a composition as described herein (e.g., a prebiotic composition, synbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein) to the subject if the level of GABA and / or GABA-producing bacteria is decreased relative to a reference. In some embodiments of any of the aspects, the step of determining if the subject has a decreased level of GABA and / or GABA-producing bacteria can comprise i) obtaining or having obtained a sample from the subject and ii) performing or having performed an assay on the sample obtained from the subject to detennine / measure the level of GABA and / or GABA-producing bacteria in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a decreased level of GABA and / or GABA-producing bacteria can comprise performing or having performed an assay on a sample obtained from the subject to detennine / measure the level of GABA and / or GABA-producing bacteria in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a decreased level of GABA and / or GABA-producing bacteria can comprise ordering or requesting an assay on a sample obtained from the subject to determine / measure the level of GABA and / or GABA-producing bacteria in the subject. In some embodiments of any of the aspects, the stepof determining if the subject has a decreased level of GABA and / or GABA-producing bacteria can comprise receiving the results of an assay on a sample obtained from the subject to determine / measure the level of GABA and / or GABA-producing bacteria in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a decreased level of GABA and / or GABA- producing bacteria can comprise receiving a report, results, or other means of identifying the subject as a subject with a decreased level of GABA and / or GABA-producing bacteria.

[0341] In one aspect of any of the embodiments, described herein is a method of treating a mental disease or disorder in a subject in need thereof, the method comprising: a) detennining if the subject has a decreased level of GABA and / or GABA-producing bacteria; and b) instructing or directing that the subject be administered a composition as described herein (e.g., a prebiotic composition, symbiotic composition, nutritional supplement, food composition, medical food, and / or pharmaceutical composition as described herein) if the level of GABA and / or GABA-producing bacteria is decreased relative to a reference. In some embodiments of any of the aspects, the step of determining if the subject has a decreased level of GABA and / or GABA-producing bacteria can comprise i) obtaining or having obtained a sample from the subject and ii) performing or having performed an assay on the sample obtained from the subject to determine / measure the level of GABA and / or GABA-producing bacteria in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a decreased level of GABA and / or GABA-producing bacteria can comprise performing or having performed an assay on a sample obtained from the subject to determine / measure the level of GABA and / or GABA-producing bacteria in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a decreased level of GABA and / or GABA-producing bacteria can comprise ordering or requesting an assay on a sample obtained from the subject to determine / measure the level of GABA and / or GABA-producing bacteria in the subject. In some embodiments of any of the aspects, the step of instructing or directing that the subject be administered a particular treatment can comprise providing a report of the assay results. In some embodiments of any of the aspects, the step of instructing or directing that the subject be administered a particular treatment can comprise providing a report of the assay results and / or treatment recommendations in view of the assay results.Definitions

[0342] For convenience, the meaning of some terms and phrases used in the specification, examples, and appended claims, are provided below. Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below. The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly rmderstood by one of ordinary skillin the art to which this invention belongs. If there is an apparent discrepancy betw een the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail.

[0343] The terms “decrease", “reduced”, “reduction”, or “inhibit” are all used herein to mean a decrease by a statistically significant amount. In some embodiments, “reduce,” “reduction" or “decrease" or “inhibit” typically means a decrease by at least 10% as compared to a reference level (e.g. the absence of a given treatment or agent) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%. at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%. at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%. at least about 98%, at least about 99%, or more. As used herein,“reduction” or “inhibition” does not encompass a complete inhibition or reduction as compared to a reference level. “Complete inhibition” is a 100% inhibition as compared to a reference level. A decrease can be preferably down to a level accepted as within the range of normal, e.g.. for an individual without a given disorder.

[0344] The terms “increased”, “increase”, “enhance”, or “activate” are all used herein to mean an increase by a statically significant amount. In some embodiments, the terms “increased”, “increase”, “enhance”, or “activate” can mean an increase of at least 10% as compared to a reference level, for example an increase of at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%. or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level, or at least about a 2-fold, or at least about a 3-fold, or at least about a 4-fold, or at least about a 5 -fold or at least about a 10-fold increase, or any increase between 2-fold and 10-fold or greater as compared to a reference level. In the context of a marker or symptom, an “increase” is a statistically significant increase in such level.

[0345] As used herein, a "subject" means a human or animal. Usually the animal is a vertebrate such as a primate, rodent, domestic animal or game animal. Primates include chimpanzees, cynomolgus monkeys, spider monkeys, and macaques, e.g., Rhesus. Rodents include mice, rats, woodchucks, ferrets, rabbits and hamsters. Domestic and game animals include cows, horses, pigs, deer, bison, buffalo, feline species, e.g., domestic cat, canine species, e.g., dog, fox, wolf, avian species, e.g., chicken, emu, ostrich, and fish, e.g., trout, catfish and salmon. In some embodiments, the subject is a mammal, e.g.. a primate, e.g., a human. The terms, “individual,” “patient” and “subject” are used interchangeably herein.

[0346] Preferably, the subject is a mammal. The mammal can be a human, non-human primate, mouse, rat, dog, cat, horse, or cow, but is not limited to these examples. Mammals other than humanscan be advantageously used as subjects that represent animal models of a mental disease or disorder. A subject can be male or female.

[0347] A subject can be one who has been previously diagnosed with or identified as suffering from or having a condition in need of treatment (e.g., a mental disease or disorder) or one or more complications related to such a condition, and optionally, have already undergone treatment for a mental disease or disorder or the one or more complications related to a mental disease or disorder. Alternatively, a subject can also be one who has not been previously diagnosed as having a mental disease or disorder or one or more complications related to a mental disease or disorder. For example, a subject can be one who exhibits one or more risk factors for a mental disease or disorder or one or more complications related to a mental disease or disorder or a subject who does not exhibit risk factors.

[0348] A “subject in need” of treatment for a particular condition can be a subject having that condition, diagnosed as having that condition, or at risk of developing that condition.

[0349] As used herein, the term "prebiotic” refers to a molecule and / or compound that modulates the composition and / or activity of the gastrointestinal microbiota, thereby conferring a beneficial physiological effect on the subject. This term encompasses but is not limited to carbohydrates (e.g.. oligosaccharides, polysaccharides, polyols such as maltitol), dietary fibers, polyphenols, lipids, proteins, peptides, and other naturally or synthetically derived compounds that are used by intestinal microbiota. The definition of a prebiotic herein includes compounds that are demonstrated to selectively stimulate the growth and / or activity of beneficial microbial species in the gastrointestinal tract, or that do not stimulate the growth and / or activity of non-beneficial microbial species in the gastrointestinal tract. The definition also includes compounds that are not currently recognized as prebiotics but may be identified as such in the future due to advances in scientific understanding. The term is intended to be inclusive of all compounds that have a prebiotic effect, irrespective of their chemical nature, origin, or the mechanism by which they exert their beneficial effects on the microbiota.

[0350] As used herein, the terms “protein" and “polypeptide" are used interchangeably to designate a series of amino acid residues, connected to each other by peptide bonds between the alpha-amino and carboxy groups of adjacent residues. The terms "protein", and "polypeptide" refer to a polymer of amino acids, including modified amino acids (e.g., phosphorylated, glycated, glycosylated, etc.) and amino acid analogs, regardless of its size or function. "Protein" and “polypeptide” are often used in reference to relatively large polypeptides, whereas the term "peptide" is often used in reference to small polypeptides, but usage of these terms in the art overlaps. The tenns "protein" and "polypeptide" are used interchangeably herein when referring to a gene product and fragments thereof. Thus, exemplary polypeptides or proteins include gene products, naturally occurring proteins,homologs, orthologs, paralogs, fragments and other equivalents, variants, fragments, and analogs of die foregoing.

[0351] In the various embodiments described herein, it is further contemplated that variants (naturally occurring or otherwise), alleles, homologs, conservatively modified variants, and / or conservative substitution variants of any of the particular polypeptides described are encompassed. As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid and retains the desired activity of the polypeptide. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles consistent with the disclosure.

[0352] A given amino acid can be replaced by a residue having similar physiochemical characteristics, e.g., substituting one aliphatic residue for another (such as lie, Vai. Leu, or Ala for one another), or substitution of one polar residue for another (such as between Lys and Arg; Glu and Asp; or Gin and Asn). Other such conservative substitutions, e g., substitutions of entire regions having similar hydrophobicity characteristics, are well known. Polypeptides comprising conservative amino acid substitutions can be tested confirm that a desired activity and specificity of a native or reference polypeptide is retained.

[0353] Amino acids can be grouped according to similarities in the properties of their side chains (in A. L. Lehninger, in Biochemistry', second ed., pp. 73-75, Worth Publishers, New York (1975)): (1) non-polar: Ala (A). Vai (V), Leu (L), He (I), Pro (P), Phe (F), Trp (W), Met (M); (2) uncharged polar: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N), Gin (Q); (3) acidic: Asp (D), Glu (E); (4) basic: Lys (K), Arg (R), His (H). Alternatively, naturally occurring residues can be divided into groups based on common side-chain properties: (1) hy drophobic: Norlcucinc, Met, Ala, Vai, Leu, He; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; (6) aromatic: Trp, Tyr, Phe. Nonconservative substitutions will entail exchanging a member of one of these classes for another class. Particular conservative substitutions include, for example; Ala into Gly or into Ser; Arg into Lys; Asn into Gin or into His; Asp into Glu; Cys into Ser; Gin into Asn; Glu into Asp; Gly into Ala or into Pro; His into Asn or into Gin; He into Leu or into Vai; Leu into He or into Vai; Lys into Arg, into Gin or into Glu; Met into Leu, into Tyr or into He; Phe into Met, into Leu or into Tyr; Ser into Thr; Thr into Ser; Trp into Tyr; Tyr into Trp; and / or Phe into Vai, into He or into Leu.

[0354] In some embodiments, the polypeptide described herein (or a nucleic acid encoding such a polypeptide) can be a functional fragment of one of the amino acid sequences described herein. As used herein, a "functional fragment” is a fragment or segment of a polypeptide which retains at least50% of the wild- type reference polypeptide’s activity’. A functional fragment can comprise conservative substitutions of the sequences disclosed herein.

[0355] In some embodiments, the polypeptide described herein can be a variant of a polypeptide sequence described herein. In some embodiments, the variant is a conservatively modified variant. Conservative substitution variants can be obtained by mutations of native nucleotide sequences, for example. A “variant," as referred to herein, is a polypeptide substantially homologous to a native or reference polypeptide, but which has an amino acid sequence different from that of the native or reference polypeptide because of one or a plurality of deletions, insertions or substitutions. Variant polypeptide-encoding DNA sequences encompass sequences that comprise one or more additions, deletions, or substitutions of nucleotides when compared to a native or reference DNA sequence, but that encode a protein or fragment thereof that retains activity of the native or reference polypeptide. A wide variety of. for example, PCR-based, site-specific mutagenesis approaches are known in the art and can be applied by the ordinarily skilled artisan to generate and test artificial variants.

[0356] A variant amino acid or DNA sequence can be at least 80%. at least 85%, at least 90%, at least 91%, at least 92%. at least 93%, at least 94%. at least 95%, at least 96%, at least 97%. at least 98%, at least 99%, or more, identical to a native or reference sequence. The degree of homology (percent identity ) between a native and a mutant sequence can be determined, for example, by comparing the two sequences using freely available computer programs commonly employed for this purpose on the world wide web (e.g. BLASTp or BLASTn with default settings).

[0357] A variant amino acid sequence can be at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%. at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more, similar to a native or reference sequence. As used herein, “similarity” refers to an identical amino acid or a conser atively substituted amino acid, as described herein. Accordingly, the percentage of “sequence similarity ” is the percentage of amino acids which is either identical or conservatively changed; e.g., “sequence similarity” = (% sequence identity)+(% conservative changes). It should be understood that a sequence that has a specified percent similarity to a reference sequence necessarily encompasses a sequence with the same specified percent identity to that reference sequence. The skilled person will be aware of various computer programs, using different mathematical algorithms, that are available to determine the identity or similarity between two sequences. For instance, use can be made of a computer program employing the Needleman and Wunsch algorithm (Needleman et al. (1970)); the GAP program in the Accelrys GCG software package (Accelerys Inc., San Diego U.S.A.): the algorithm of E. Meyers and W. Miller (Meyers et al. (1989)) which has been incorporated into the ALIGN program (version 2.0); or more preferably the BLAST (Basic Local Alignment Tool using default parameters); see e.g.. US Patent 10.023.890. the content of which is incorporated by reference herein in its entirety.

[0358] As used herein, the phrase “maintains the same function’’, when used in reference to an enzyme, means the enzyme catalyzes the same reaction as a reference polypeptide.

[0359] In some embodiments, sequencing comprises 16S rRNA gene sequencing, which can also be referred to as “16S ribosomal RNA sequencing’’, “16S rDNA sequencing” or “16s rRNA sequencing”. Sequencing of the 16S rRNA gene can be used for genetic studies as it is highly conserved between different species of bacteria, but it is not present in eukaryotic species. In addition to highly conserved regions, the 16S rRNA gene also comprises nine hypervariable regions (V1-V9) that vary by species. 16S rRNA gene sequencing typically comprises using a plurality of universal primers that bind to conserved regions of the 16S rRNA gene, PCR amplifying the bacterial 16S rRNA gene regions (including hypervariable regions), and sequencing the amplified 16S rRNA genes with a next-generation sequencing technology as described herein (see also e.g.. US Patents 5.654,418; 6,344,316; and 8.889.358; and US Patent Application Numbers US 2013 / 0157265 and US 2018 / 0195111, which are incorporated by reference in their entireties).

[0360] In some embodiments, the methods described herein relate to measuring, detecting, or determining the level of at least one marker. As used herein, the term "detecting" or “measuring” refers to observing a signal from, e.g. a probe, label, or target molecule to indicate the presence of an analyte in a sample. Any method known in the art for detecting a particular label moiety can be used for detection. Exemplar}’ detection methods include, but are not limited to, spectroscopic, fluorescent, photochemical, biochemical, immunochemical, electrical, optical or chemical methods. In some embodiments of any of the aspects, measuring can be a quantitative observation.

[0361] As used herein, the terms "treat.” "treatment," "treating,” or “amelioration” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a condition associated with a disease or disorder, e.g., a mental disease or disorder. The term “treating" includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder associated with a mental disease or disorder. Treatment is generally “effective" if one or more symptoms or clinical markers are reduced. Alternatively, treatment is “effective" if the progression of a disease is reduced or halted. That is, “treatment" includes not just the improvement of symptoms or markers, but also a cessation of, or at least slowing of, progress or worsening of symptoms compared to what would be expected in the absence of treatment. Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, remission (whether partial or total), and / or decreased mortality, whether detectable or undetectable. The term "treatment" of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment).

[0362] As used herein, the term “pharmaceutical composition'’ refers to an active agent in combination with a pharmaceutically acceptable carrier e.g., a carrier commonly used in the pharmaceutical industry. The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be a carrier other than water. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be a cream, emulsion, gel, liposome, nanoparticle, and / or ointment. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be an artificial or engineered carrier, e.g.. a carrier that the active ingredient would not be found to occur in or within nature.

[0363] As used herein, the term "administering," refers to the placement of a compound as disclosed herein into a subject by a method or route which results in at least partial delivery of the agent at a desired site. Pharmaceutical compositions comprising the compounds disclosed herein can be administered by any appropriate route which results in an effective treatment in the subject. In some embodiments, administration comprises physical human activity, e.g.. act of ingestion, an injection, an act of application, and / or manipulation of a delivery device or machine. Such activity7can be performed, e.g., by a medical professional and / or the subject being treated.

[0364] The term “statistically significant" or “significantly" refers to statistical significance and generally means a two standard deviation (2SD) or greater difference or a p-value of less than 0.05.

[0365] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean ±1%.

[0366] As used herein, the term “comprising” means that other elements can also be present in addition to the defined elements presented. The use of “comprising” indicates inclusion rather than limitation.

[0367] The term "consisting of refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment.

[0368] As used herein the term "consisting essentially of refers to those elements required for a given embodiment. The term permits the presence of additional elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment of the invention.

[0369] The singular terms "a," "an," and "the" include plural referents unless context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. Although methods and materials similar or equivalent to those described hereincan be used in the practice or testing of this disclosure, suitable methods and materials arc described below. The abbreviation, "e.g." is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation "e.g." is synonymous with the term "for example."

[0370] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.[00371 ( Unless otherwise defined herein, scientific and technical terms used in connection with the present application shall have the meanings that are commonly understood by those of ordinary skill in the art to which this disclosure belongs. It should be understood that this invention is not limited to the particular methodology, protocols, and reagents, etc., described herein and as such can vary. The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention, which is defined solely by the claims. Definitions of common terms in cell biology, immunology, and molecular biology can be found in The Merck Manual of Diagnosis and Therapy, 20th Edition, published by Merck Sharp & Dohme Corp.. 2018 (ISBN 0911910190, 978-0911910421); Robert S. Porter et al. (eds.), The Encyclopedia of Molecular Cell Biology and Molecular Medicine, published by Blackwell Science Ltd., 1999-2012 (ISBN 9783527600908); and Robert A. Meyers (ed.). Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8); Immunolog}7by Werner Luttmann, published by Elsevier, 2006; Janeway's Immunobiology7, Kenneth Murphy , Allan Mowat, Casey Weaver (eds.), W. W. Norton & Company, 2016 (ISBN 0815345054, 978-0815345053); Lewin's Genes XI, published by Jones & Bartlett Publishers, 2014 (ISBN- 1449659055); Michael Richard Green and Joseph Sambrook, Molecular Cloning: A Laboratory7Manual. 4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (2012) (ISBN 1936113414); Davis et al., Basic Methods in Molecular Biology, Elsevier Science Publishing, Inc., New York, USA (2012) (ISBN 044460149X); Laboratory Methods in Enzymology: DNA, Jon Lorsch (ed.) Elsevier, 2013 (ISBN 0124199542); Current Protocols in Molecular Biology (CPMB), Frederick M. Ausubel (ed.), John Wiley and Sons, 2014 (ISBN 047150338X. 9780471503385), Current Protocols in Protein Science (CPPS), John E. Coligan (ed.), John Wiley and Sons. Inc., 2005; and Current Protocols in Immunology7(CPI) (John E. Coligan, ADA M Kruisbeek, David H Margulies. Ethan M Shevach. Warren Strobe, (eds.) John Wiley and Sons. Inc., 2003 (ISBN 0471142735. 9780471142737), the contents of which are all incorporated by reference herein in their entireties.

[0372] Other terms are defined herein within the description of the various aspects of the invention.

[0373] All patents and other publications; including literature references, issued patents, published patent applications, and co-pending patent applications; cited throughout this application are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that might be used in connection with the technology described herein. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents.|00374| The description of embodiments of the disclosure is not intended to be exhaustive or to limit the disclosure to the precise form disclosed. While specific embodiments of, and examples for, the disclosure are described herein for illustrative purposes, various equivalent modifications are possible within the scope of the disclosure, as those skilled in the relevant art will recognize. For example, while method steps or functions are presented in a given order, alternative embodiments may perform functions in a different order, or functions may be performed substantially concurrently. The teachings of the disclosure provided herein can be applied to other procedures or methods as appropriate. The various embodiments described herein can be combined to provide further embodiments. Aspects of the disclosure can be modified, if necessary, to employ the compositions, functions and concepts of the above references and application to provide yet further embodiments of the disclosure. Moreover, due to biological functional equivalency considerations, some changes can be made in protein structure without affecting the biological or chemical action in kind or amount. These and other changes can be made to the disclosure in light of the detailed description. All such modifications are intended to be included w ithin the scope of the appended claims.

[0375] Specific elements of any of the foregoing embodiments can be combined or substituted for elements in other embodiments. Furthermore, while advantages associated with certain embodiments of the disclosure have been described in the context of these embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the disclosure.

[0376] Some embodiments of the technology described herein can be defined according to any of the following numbered paragraphs:1. A prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bacteroides in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase the relative and / or absolute abundance of the at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gutof the mammalian subject is increased when the probiotic composition is consumed by the mammalian subject relative to a control. A prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase relative abundance of the at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control. A prebiotic composition for decreasing the relative and / or absolute abundance of at least one bacterium of the family Enterobacteriaceae in the gut of a mammalian subject, the prebiotic composition comprising an amount of maltitol effective to decrease the relative and / or absolute abundance of the at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject compared to other formulations containing a sweetener that is not maltitol. The prebiotic composition of any one of paragraphs 1-3, wherein the effective amount of maltitol is comprised by a unit amount of the prebiotic composition. The prebiotic composition of any one of paragraphs 1-4, wherein the effective amount of maltitol is a concentration of at least 1% to at most 100% w / w maltitol. The prebiotic composition of any one of paragraphs 1-5, wherein the effective amount of maltitol is 0.5 g to 25g per unit or serving. The prebiotic composition of any one of paragraphs 1-6, wherein the form of maltitol is selected from the group consisting of maltitol syrup, maltitol powder, maltitol crystals, and maltitol gel. The prebiotic composition of paragraph 7, wherein the maltitol syrup comprises about 5% sorbitol. The prebiotic composition of any one of paragraphs 1-8, wherein at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacleroides or the at least one bacterium of die genus Bifidobacterium internalizes, is supported by, and / or metabolizes the effective amount of maltitol in the composition in the gut of the mammalian subject. The prebiotic composition of any one of paragraphs 1-9, wherein the mammalian subject is a human. The prebiotic composition of any one of paragraphs 1-10, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing. and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of thegenus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of tire genus Bifidobacterium by at least 1% in the gut of the mammalian subject. The prebiotic composition of any one of paragraphs 1-11, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. The prebiotic composition of any one of paragraphs 1-12. wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. The prebiotic composition of any one of paragraphs 1-13, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject. The prebiotic composition of any one of paragraphs 1-14, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject. The prebiotic composition of any one of paragraphs 1-15, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacteroides or the at least one bacterium of the genus Bifidobacterium in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder. The prebiotic composition of paragraph 16, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa.bingc-cating disorder, avoidant / rcstrictivc food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR-MDD), major depressive disorder and its subtypes (melancholic depression, aty pical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor. Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof. The prebiotic composition of paragraph 16 or 17, wherein treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder. The prebiotic composition of paragraph 18, wherein at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof. The prebiotic composition of any one of paragraphs 1-19, wherein the prebiotic composition further comprises at least one excipient selected from the group consisting of encapsulation materials (e.g.. chitosan, wax. and gelatin), solubilizers (e.g., TWEEN 80 or SPAN 60), bulking agents (e.g., maltodextrin or microcry stalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g., ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof. The prebiotic composition of any one of paragraphs 1-20, wherein the prebiotic composition further comprises at least one additional prebiotic selected from the group consisting of amino acid (e.g., arginine, glutarate, and ornithine), biotin, fructooligosaccharide, galactooligosaccharide, hemi cellulose (e.g., arabinoxy lan, xylan, xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, gum (e.g., guar gum, gum arabic, and carrageenan), oligofructose, oligodextrose, tagatose, resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide, pectin (e.g., xylogalactouronan. citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary' fiber (e.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccharide, and polyamine (e.g.. spermidine, putrescine). The prebiotic composition of any one of paragraphs 1-21, wherein the prebiotic composition is formulated for delivery to the gut of a mammalian subject. The prebiotic composition of any one of paragraphs 1-22, wherein the prebiotic composition is in the form of a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a candy, a sy rup, an elixir, alozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof. The prebiotic composition of any one of paragraphs 3-23, wherein the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence selected from Table 7. The prebiotic composition of any one of paragraphs 3-24, wherein the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence comprising one of SEQ ID NOs: 46-89 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 46-89. The prebiotic composition of any one of paragraphs 3-25, wherein the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8. The prebiotic composition of any one of paragraphs 3-26, wherein the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 8. The prebiotic composition of any one of paragraphs 1-27, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium selected from the “increased” column of Table 11. The prebiotic composition of any one of paragraphs 1-28, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a 1 S sequence selected from Table 12. The prebiotic composition of any one of paragraphs 1-29, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence comprising one of SEQ ID NOs: 207-360 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 207-360. The prebiotic composition of any one of paragraphs 1-30, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Tabic 13. The prebiotic composition of any one of paragraphs 1-31, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 13or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 13. The prebiotic composition of any one of paragraphs 1-32, wherein the prebiotic increases the relative and / or absolute abundance of a combination of bacteria selected from Table 16. The prebiotic composition of any one of paragraphs 1-33, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium selected from the “decreased” column of Table 11.The prcbiotic composition of any one of paragraphs 1-34, wherein the prcbiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence selected from Table 14. The prebiotic composition of any one of paragraphs 1-35, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence comprising one of SEQ ID NOs: 361-596 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 361-596. The prebiotic composition of any one of paragraphs 1-36, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 15. The prebiotic composition of any one of paragraphs 1-37, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 15or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 15. A synbiotic composition comprising the prebiotic composition of any one of paragraphs 1-38 and at least one bacterial species. A synbiotic composition comprising maltitol and at least one bacterial species. The synbiotic composition of any one of paragraphs 39-40. wherein the synbiotic composition comprises an amormt of maltitol effective to increase the growth rate and / or metabolic activity7of at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject. The synbiotic composition of any one of paragraphs 39-41. wherein the synbiotic composition comprises an amormt of maltitol effective to increase the growth rate and / or metabolic activity of at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by tire mammalian subject. The synbiotic composition of any one of paragraphs 39-42, wherein the synbiotic composition comprises an amount of maltitol effective to decrease the growth rate and / or metabolic activity of at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject. The synbiotic composition of any one of paragraphs 39-43, wherein the effective amormt of maltitol is comprised by a unit amount of the synbiotic composition. The synbiotic composition of any one of paragraphs 39-44, wherein the effective amount of maltitol is a concentration of at least 1% to at most 100% w / w maltitol.The synbiotic composition of any one of paragraphs 39-45, wherein the at least one bacterial species is at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species encodes and / or expresses a protein or protein complex that internalizes and / or metabolizes maltitol. The synbiotic composition of any one of paragraphs 39-46, wherein the protein or protein complex that internalizes and / or metabolizes maltitol is selected from Table 9 or Table 10. The synbiotic composition of any one of paragraphs 39-47, wherein the protein or protein complex that internalizes and / or metabolizes maltitol is maltitol dehydrogenase or a-glucosidase. The synbiotic composition of any one of paragraphs 39-48, wherein the protein or protein complex that internalizes maltitol comprises one of SEQ ID NOs: 171-206 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 171-206 that maintains its function as a polypeptide. The synbiotic composition of any one of paragraphs 39-49, wherein the protein or protein complex that metabolizes maltitol comprises one of SEQ ID NOs: 90-170 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 90-170 that maintains its function as a polypeptide. The synbiotic composition of any one of paragraphs 39-50. wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence selected from Table 5 or Table 12. The synbiotic composition of any one of paragraphs 39-51. wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or 207-360 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 1-45 or 207-360. The synbiotic composition of any one of paragraphs 39-52, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 6 or Table 13. The synbiotic composition of any one of paragraphs 39-53, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 6 or Table 13 or a nucleic acid sequence that is at least 95% identical a genome selected from Table 6 or Table 13. The synbiotic composition of any one of paragraphs 39-54, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a combination of bacteria selected from Table 16. The synbiotic composition of any one of paragraphs 39-55, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is dried and / or viable.The synbiotic composition of any one of paragraphs 39-56, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is freeze- dried and / or spray -dried. The synbiotic composition of any one of paragraphs 39-57, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is a viable, isolated bacterial species. The synbiotic composition of any one of paragraphs 39-58, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is present at a concentration of at a concentration of at least 101colony forming units per gram (CFU / g) to at most 1013CFU / g. The synbiotic composition of any one of paragraphs 39-59, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is at least one bacterium of the genus Bacteroides. The synbiotic composition of any one of paragraphs 39-60, wherein the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifaciens. B. caccae. B. caecicola, B. caecigallinarum, B. cellulosilyticus, B. cellulosolvens. B. clarus, B. coagulans, B. coprocola. B. coprophilus, B. coprosuis. B. dorei, B. eggerthii, B. faeci chinchill ae. B. faecis, B. finegoldii, B. fluxus, B. fragilis, B. galacturonicus, B. gallinaceum, B. gallinarum, B. goldsteinii, B. graminisolvens, B. helcogene, B. intestinalis, B. luti. B. massiliensis, B. nordii, B. oleiciplenus. B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifaciens, B. putredinis, B. pyogenes, B. reticulotermitis, B. rodentium, B. salanitro is, B. salyersiae, B. sartorii, B. stercoris, B. thetaiotaomicron, B. uniformis, B. vulgatus, and B. xylanisolvens. The synbiotic composition of any one of paragraphs 39-61. wherein the at least one bacterium of the genus Bacteroides comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 1-45. The synbiotic composition of any one of paragraphs 39-62, wherein the at least one bacterium of the genus Bacteroides comprises a genome selected from Table 6 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 6. The synbiotic composition of any one of paragraphs 39-63, wherein the at least one bacterium of the genus Bacteroides encodes and expresses a protein or protein complex that internalizes and / or metabolizes maltitol. The synbiotic composition of any one of paragraphs 39-64, wherein the protein or protein complex that internalizes and / or metabolizes maltitol comprises one of SEQ ID NOs: 179-295 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 179-295 that maintains its function as a polypeptide.I l l66. The synbiotic composition of any one of paragraphs 39-65, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides internalizes and / or metabolizes the maltitol in the composition in the gut of a mammalian subject.67. The synbiotic composition of any one of paragraphs 39-66, wherein the mammalian subject is a human.68. The synbiotic composition of any one of paragraphs 39-67, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides by at least 1% in the gut of the mammalian subject.69. The synbiotic composition of any one of paragraphs 39-68, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.70. The synbiotic composition of any one of paragraphs 39-69. wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.71. The synbiotic composition of any one of paragraphs 39-70, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or semm, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject.'ll. The synbiotic composition of any one of paragraphs 39-71, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.The synbiotic composition of any one of paragraphs 39-72, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacteroides in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder. The synbiotic composition of paragraph 39-73, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxietydisorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR-MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof. The synbiotic composition of paragraph 73 or 74, wherein treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder. The synbiotic composition of paragraph 75, wherein at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity-, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof. The synbiotic composition of any one of paragraphs 39-76, wherein the synbiotic composition further comprises at least one excipient selected from the group consisting of encapsulation materials (e.g., chitosan, wax, and gelatin), solubilizers (e.g., Tween 80 or Span 60), bulking agents (e.g., maltodextrin or microcrystalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g., ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof. The synbiotic composition of any one of paragraphs 39-77, wherein the synbiotic composition further comprises at least one additional prebiotic selected from the group consisting of amino acid (e.g., arginine, glutarate, and ornithine), biotin, fructooligosaccharide, galactooligosaccharide, hemi cellulose (e.g., arabinoxylan. xylan, xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, gum (e.g.. guargum, gum arabic, and carrageenan), oligofructo sc, oligodextrose, tagatosc, resistant maltodcxtrins (e.g., resistant starch), trans-galactooligosaccharide, pectin (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fiber (e.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccliaridc. and polyamine (e.g., spermidine, putrescine). The symbiotic composition of any one of paragraphs 39-78, wherein the symbiotic composition is formulated for delivery to the gut of a mammalian subject. The symbiotic composition of any one of paragraphs 39-79, wherein the symbiotic composition is in the form of a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof. A nutritional supplement comprising the prebiotic composition of any one of paragraphs 1-38 or the synbiotic composition of any one of paragraphs 39-80. The nutritional supplement of paragraph 81, wherein the prebiotic composition or the synbiotic composition is at a concentration of at least 1% to at most 70% in the nutritional supplement. The nutritional supplement of any one of paragraphs 81-82. wherein the nutritional supplement is formulated for delivery to the gut of a mammalian subject. The nutritional supplement of any one of paragraphs 81-83. wherein the nutritional supplement is in the form of a probiotic, a prebiotic, a sy nbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof. A food composition comprising the prebiotic composition of any one of paragraphs 1-38 or the synbiotic composition of any one of paragraphs 39-80. The food composition of paragraph 85, wherein the food composition is selected from the group consisting of milk, y ogurt, plant-based dairy alternatives (e.g., oat milk, almond milk, coconut milk, soy milk, pea milk, etc.), soft drinks (e.g., soda, carbonated water, etc.) fermented milk, protein shakes, fruit juice (e.g., apple juice, orange juice, grapefruit juice, grape juice, etc.), nondairy fermented beverages (e.g., kombucha, etc.), vegetable juices (e.g. carrot juice, tomato juice, etc.), alcoholic beverages (e.g., cairned cocktail, alcoholic cider, etc.), sauces (e.g., gravy , tomato sauce, barbeque sauce, etc.), broth and stock (e.g., chicken stock, beef broth, vegetable broth, etc.), syrups, tea beverages (e.g., tea-based powder, milk tea, etc.), coffee beverages (e.g., cold brew, latte, iced coffee), yogurt beverages, or cereal-based beverages (e.g., rice milk, beer, barley tea, etc.). The food composition of any one of paragraphs 85-86. wherein the food composition is selected from the group consisting of granola bars, meal replacement bars, protein bars, fruit bars, breakfast cereals, pastas, bread products (e.g.. loaves, buns, croutons, etc.), condiments and relishes (e.g., ketchup, relish, etc.), frosting, gelatin and pudding, cough drops, or jams and jellies.The food composition of any one of paragraphs 85-87, wherein the food composition is selected from the group of food concentrates consisting of bouillon concentrate, soup concentrate, or gravy concentrate. The food composition of any one of paragraphs 85-88, wherein the food composition is a confectionary selected from the group consisting of a chocolate composition, a chocolate analogue composition, chewing gum, soft chew candy, gummy candy, or hard candy. The food composition of any one of paragraphs 85-89. wherein the food composition is a frozen confection (e.g., ice cream, sorbet, sherbet, frozen yogurt or water ice), is a frozen confection product comprising a frozen composition and a chocolate composition or a chocolate analogue composition wherein the chocolate composition or a chocolate analogue composition is in the form of a coating on the frozen composition and / or inclusions located within the frozen composition and / or a ripple or swirl of sauce. The food composition of any one of paragraphs 85-90, wherein the prebiotic composition or the symbiotic composition is at a concentration of at least 1% to at most 70% in the food composition. A medical food for the improvement of mood, the promotion of relaxation, the promotion of a calming mood state, and / or the treatment of depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, comprising an effective amount of maltitol, wherein the medical food is formulated to provide a daily dosage of maltitol in the effective amount of 0.5g to 25g based on a serving size of about 0.8g to 125g of said medical food taken up to three times a day. A medical food for the improvement of mood, the promotion of relaxation, the promotion of a calming mood state, and / or the treatment of depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, comprising an effective amount of maltitol and at least one bacterial species, wherein the medical food is formulated to provide (a) a daily dosage of maltitol in the effective amount of 0.5 g to 25 g and (b) a daily dosage of the at least one bacterial species of 101CFU / g to 1013CFU / g, based on a serving size of about 0.8g to 125 g of said medical food taken up to three times a day. The use of maltitol in the food composition of any one of paragraphs 85-91 or in the medical food of any one of paragraphs 92-93 for replacing sugar in the food composition or in the medical food. A pharmaceutical composition comprising the prebiotic composition of any one of paragraphs 1- 38 or the synbiotic composition of any one of paragraphs 39-80, and a pharmaceutically acceptable carrier. The pharmaceutical composition of paragraph 95, wherein the prebiotic composition or the synbiotic composition is at a concentration of at least 1% to at most 70% in the pharmaceutical composition.The pharmaceutical composition of any one of paragraphs 95-96, wherein the pharmaceutical composition is formulated for delivery' to the gut of a mammalian subject. The pharmaceutical composition of any one of paragraphs 95-97, wherein the pharmaceutical composition is in the form of a probiotic, a prebiotic, a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof. The use of maltitol in the preparation of a medicament for the treatment of a disease or disorder related to low or reduced GABA levels. . The use of paragraph 99, wherein the disease or disorder related to low or reduced GABA levels is a mental disease or disorder. . The use of paragraph 100, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiffperson syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof. . A method of improving mood in a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98. . A method of promoting relaxation and / or promoting a calming mood state in a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98. . A method of reducing stress or anxiety in a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80. the nutritional supplement of any one ofparagraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98.. A method of increasing the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98. . A method of increasing the production rate of y-aminobutyric acid (GABA) by at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides in the gut of a mammalian subject or at least one bacterium of the genus Bifidobacterium, and / or increasing the concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80. the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98. . A method of treating depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, the method comprising administering an effective amount of the prebiotic composition of any one of paragraphs 1-38, the sy nbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98. . The method of any one of paragraphs 102-107, wherein the mammalian subject is a human.. The method of any one of paragraphs 102-108, wherein the administering is to the gut of die subject. . The method of any one of paragraphs 102-109, wherein improving mood in the mammalian subject, promoting relaxation and / or promoting a calming mood state in the mammalian subject, and / or reducing stress and / or anxiety in the mammalian subject is measured by a test selected from the group consisting of the Hopkins Symptom Checklist-25, Hamilton Depression Rating Scale, the Beck Depression Inventory, Positive and Negative Affect Schedule, Profile of Mood states (POMS) Questionnaire, a friendliness score. General Anxiety Disorder Questionnaire-7(GAD-7), Visual Analog Mood Scale, VAS / Likert Seale, Perceived Stress Seale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Center for Epidemiologic Studies Depression Scale, Geriatric Depression Scale, Montgomer -Asberg Depression Rating Scale, Cohen’s Perceived Stress Scale. Holmes and Rahe Stress Scale, World Health Organization Quality of Life, Short Form Health Survey (SF-36), and EuroQol five dimensions questiomiaire, or a combination thereof. . The method of any one of paragraphs 102-110, wherein mood is improved in the subject by at least 5%. . The method of any one of paragraphs 102-111, wherein relaxation is promoted in the subject by at least 5%. . The method of any one of paragraphs 102-112, wherein a calming mood state is promoted in the subject by at least 5%. . The method of any one of paragraphs 102-113, wherein stress and / or anxiety is reduced in the subject by at least 5%. . The method of any one of paragraphs 102-114. wherein at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium internalizes and / or metabolizes and / or is supported by maltitol from the composition in the gut of the mammalian subject. . The method of any one of paragraphs 102-115, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject. . The method of any one of paragraphs 102-116, wherein the increase of the relative and / or absolute abundance of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium is determined by:(i) quantifying the at least one maltitol-intemalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject before ingestion of the composition;(ii) quantifying the at least one maltitol-intcrnalizing, and / or maltitol-mctabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject after ingestion of the composition;(iii) and determining the relative and / or absolute abundance of the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of die genus Bifidobacterium from the data from (ii) compared to the data from (i). . The method of paragraph 117, wherein quantification of (i) and / or (ii) comprises nucleic acid sequencing. . The method of paragraph 118, wherein the nucleic acid sequencing comprises 16S metagenomic sequencing, shotgun metagenomic sequencing, and / or amplification and sequencing of the 16S gene by polymerase chain reaction and sequencing. . The method of paragraph 117. wherein quantification of (i) and / or (ii) comprises non- sequencing-based methods. . The method of any one of paragraphs 102-120. wherein the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifaciens. B. caccae, B. caecicola, B. caecigallinarum, B. cellulosilyticus, B. cellulosolvens. B. clarus, B. coagulans, B. coprocola. B. coprophilus, B. coprosuis. B. dorei, B. eggerthii, B. faecichinchillae, B. faecis, B. finegoldii, B. fiuxus, B. fragilis, B. galacturonicus, B. gallinaceum, B. gallinarum, B. goldsteinii, B. gramini solvens, B. helcogene, B. intestinalis, B. luti, B. massiliensis, B. nordii, B. oleiciplenus, B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifiaciens, B. putredinis, B. pyogenes, B. reticulotermitis, B. rodentium, B. salanitronis, B. salyersiae, B. sartorii, B. stercoris, B. thetaiotaomicron, B. uniformis, B. vulgatus, and B. xylanisolvens. . The method of any one of paragraphs 102-121, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobuty ric acid (GABA) by the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. . The method of any one of paragraphs 102-122, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effectiveamount of maltitol increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject. . The method of any one of paragraphs 102-123, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject. . The method of any one of paragraphs 102-124, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.. The method of any one of paragraphs 102-125, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) treats or improves symptoms of a mental disease or disorder. . The method of paragraph 126, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR-MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof. . The method of paragraph 126 or 127, wherein treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder. . The method of paragraph 128, wherein at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof. . The method of any one of paragraphs 102-129, wherein the method further comprises administering at least one mood-improving therapeutic to the subject.. The method of any one of paragraphs 102-130, wherein the method further comprises administering at least one anti-depression, anti-anxiety, and / or anti-stress therapeutic to the subject. . The method of any one of paragraphs 102-131, wherein the method further comprises identifying a subject in need of treatment by determining whether tire subject would benefit from an increase in endogenous GABA and / or GABA-producing bacteria by measuring an initial amount of GABA in the subject's stool. . The method of paragraph 132, wherein the initial amount of endogenous GABA in the subject's stool is below about 300 pg per gram (pg / g), about 200 pg / g, about 100 pg / g. about 50 pg / g, about 20 pg / g, or about 10 pg / g of wet or dry stool. . The method of paragraph 132 or 133, wherein the amount of GABA in the subject's stool is increased relative to the initial amount after administering the maltitol formulation. . The method of any one of paragraphs 102-134, wherein the method further comprises identifying a subject in need of treatment by determining whether the subject would benefit from an increase in endogenous GABA by measuring an initial amount of GABA-producing bacteria in the subject's stool. . The method of paragraph 135, wherein the initial amount of GABA-producing bacteria in the subject's stool is less than about 50%, about 40%, about 30%. about 20%, about 10%, about 5%, or about 1% of total bacteria as measured by 16S sequence mapping. . The method of paragraph 135 or 136, wherein the amount of GABA-producing bacteria in the subject's stool is increased relative to the initial amount after administering the maltitol formulation. . The method of any one of paragraphs 135-137, wherein the GABA-producing bacteria are selected from Table 5, Table 6, Table 11 (e.g., “increased” column), Table 12, or Table 13.. The method of any one of paragraphs 135-138, wherein the GABA-producing bacteria encode or express a protein or protein complex that internalizes and / or metabolizes maltitol selected from Table 9 or Table 10. . The method of any one of paragraphs 135-139, wherein the GABA-producing bacteria comprise at least one bacterium of the genus Bacleroides. . The prebiotic composition of any one of paragraphs 1-38, wherein the prebiotic composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the prebiotic composition is for the use of any one of paragraphs 102-140. . The synbiotic composition of any one of paragraphs 39-80. wherein the synbiotic composition is comprised by a packaged food product, wherein the package of the packaged food product isassociated with or comprises indicia that the synbiotic composition is for the use of any one of paragraphs 102-140. . The nutritional supplement of any one of paragraphs 81-84, wherein tire nutritional supplement is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the nutritional supplement is for the use of any one of paragraphs 102-140. . The food composition of any one of paragraphs 85-91, wherein the food composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the food composition is for the use of any one of paragraphs 102-140. . The medical food of any one of paragraphs 92-93. wherein the medical food is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the medical food is for the use of any one of paragraphs 102-140. . The pharmaceutical composition of any one of paragraphs 95-98, wherein the pharmaceutical composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the pharmaceutical composition is for the use of any one of paragraphs 102-140. . The prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98 for use in a method of improving mood in a mammalian subject. . The prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98 for use in a method of promoting relaxation and / or promoting a calming mood state in a mammalian subject. . The prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84. the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93. or the pharmacal composition of any one of paragraphs 95-98 for use in a method of reducing stress or anxiety in a mammalian subject. . The prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of anyone of paragraphs 39-80. the nutritional supplement of any one of paragraphs 81-84. the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93. or the pharmaceutical composition of any one of paragraphs 95-98 for use in a method of increasingthe relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject.151. The prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84. the food composition of any one of paragraphs 85-91, the medical food of any one of paragraphs 92-93. or the pharmacal composition of any one of paragraphs 95-98 for use in a method of increasing the production rate of y-aminobutyric acid (GABA) by at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, and / or increasing the concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a mammalian subject.152. The prebiotic composition of any one of paragraphs 1-38, the synbiotic composition of any one of paragraphs 39-80, the nutritional supplement of any one of paragraphs 81-84, the food composition of any one of paragraphs 85-91. the medical food of any one of paragraphs 92-93, or the pharmaceutical composition of any one of paragraphs 95-98 for use in a method of treating depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof.

[0377] The technology described herein is further illustrated by the following examples which in no way should be construed as being further limiting.EXAMPLESExample 1

[0378] The gut microbiome is malleable and strongly influenced by diet. Prebiotics. food ingredients that promote the growth of beneficial bacteria and / or inhibit the growth of non-beneficial bacteria, can be used to modulate the microbiome in a health and well-being promoting manner. As such, a prebiotic that selectively supports GABA-producing Bacteroides in the gut microbiome can be used to increase GABA levels and improve stress, anxiety, or low mood. Similarly, a prebiotic that does not support the growth of Enterobacteriaceae can be used to lower the abundance of the proinflammatory family of bacteria in the gut microbiome to reduce inflammation and disease incidence. Of note, prebiotic ingredients such as these can be swapped for similar ingredients in existing food products to create foods that are more microbiome friendly. In particular, non-sucrose sweeteners are especially attractive as alternatives to sucrose, as they can make food products healthier, more palatable, andhave less blood glucosc-modulating potential. However, their probiotic potential is largely understudied (Plaza-Diaz et al., 2020; Ruiz-Ojeda et al., 2019).

[0379] Described herein is the investigation of the prebiotic potential, relevant to the microbiome- gut-brain axis, of a panel of sweeteners. To do this, the sweeteners were first screened against Enterobacteriaceae representatives and a GABA producer in monoculture to identify sweeteners with the potential to support GABA producing Bacteroides without supporting Enterobacteriaceae. The top candidate prebiotic sweeteners were further tested in an ex-vivo human gut simulator model to understand the effect of the sweeteners in mixed, fecal-derived communities on fecal bacterial community composition and GABA production.

[0380] Maltitol was identified as (1) a prebiotic sweetener that increases Bacteroides and GABA production, (2) a prebiotic for use to reduce stress or low mood symptoms, (3) a prebiotic sweetener with minimal Enterobacteriaceae-supporting potential, and (4) as a prebiotic for use to reduce Enterobacteriaceae-associated inflammation and disease. Maltitol is a sugar alcohol, known as a polyol, primarily utilized as a sugar substitute. Structurally similar to sugar but with fewer calories, maltitol is a water-soluble white crystalline powder, highly soluble in water, with a slightly sweet taste and good texture, making it attractive as a sucrose alternative for food products. Maltitol reaches the colon primarily undigested (Plaza-Diaz et al., 2020; Ruiz-Ojeda et al., 2019), which is an aspect of its prebiotic potential.Methods

[0381] Monoculture Screen of the Sweeteners Panel

[0382] Preparation of the Monoculture Screening Plate

[0383] To prepare tire Monoculture Screening Plate, Sweeteners (see e.g., Table 1) were added to a 96-well plate at 4000 ug / mL.

[0384] Table 1. Sweetener panel tested in the Monoculture Screening Plate.

[0385] Preparation of the Bacterial Panel for the Monoculture Screening Plate

[0386] Enterobacteriaceae representatives Escherichia coli, Shigella sonnei, Enterobacter cloaceae, and Salmonella typhimurium were selected to screen against the sweeteners in monoculture (see e.g..Tabic 2). Additionally, Bacteroides xylanisolvens, a prominent strain in the human gut microbiomc, was included as a representative GABA producer. Bacterial strains were obtained from the American Type Culture Collection (ATCC) or the Deutsche Sammlung von Mikroorganismen und Zellkulturen collection (DSM) as indicated in Table 2.

[0387] Table 2. Members of the panel of bacteria selected for screening in the Monoculture Screening Plate.

[0388] Performing the Monoculture Screen

[0389] All growth of bacteria was performed under an anaerobic environment (5% CO2, 5%H2, 90% N2) and all non-medium materials were reduced for at least 24 hours prior to use. Stocks of each strain were revived on Brucella Blood Agar (BBA) (ANAEROBE SYSTEMS, California, USA) and were grown for 24-72 hours at 37°C. Cell suspensions were prepared for inoculation into the Monoculture Screening Plate by transferring cells from a BBA plate to a minimal medium.

[0390] At the time of testing, Brucella broth (ANAEROBE SYSTEMS, California. USA) was added to wells in each plate to serve as a positive growth control. Working with one plate per strain, the cell suspension was added to each well, including to a row of blank wells to serve as negative controls. Each strain was performed in duplicate. Plates were incubated for 24-72 hours at 37°C. The percent growth of each ingredient-strain combination was calculated based on the average cell density of an ingredient-strain combination compared to the average cell density of the negative controls for the respective strain.

[0391] Screening of Candidate Sweeteners in an Ex- Vivo Gut simulator model

[0392] Testing the Candidate Sweeteners in the Gut Simulator

[0393] The top candidate sweeteners and non-candidate controls from the monoculture screen were tested in a human gut simulator model, a fecal fermentation model. Namely, sweeteners that lead to expansive growth of Enterobacteriaceae were not included in the gut simulator model screen, except L-lyxose and L-arabinose which were screened as controls.

[0394] All experiments in the Human Gut Simulator (HuGS) were performed under anaerobic conditions (5% CO2, 5%H2, 90% N2) in an anaerobic chamber (COY LABORATORY PRODUCTS; Michigan, USA). Gut simulator communities were derived from six human donors from the HOLOBIOME Donor Vault, Donors 1-6.

[0395] All gut simulator experiments were performed in a rich medium, supplemented with 2.5 ml / L 10 g / mL Monosodium glutamate solution, at pH 5.0, 5.5, 6.0, 6.5, and / or 7.0, respectively. Inositol, L- Arabinose, and L-lyxose were tested in Donor 1 and Donor 2 under pH 7.0 only. Maltitol was tested initially in Donors 1 and 2 at pH 7.0, and then with all human donors under all pH conditions. The negative control communities in all experiments for each donor were grown in tire base rich medium without additional carbon sources added; this was performed at each pH level tested in an experiment respectively. Ingredients were tested at relevant doses, described in Table 3, in duplicate across the gut simulator models. The communities were incubated for 24-48 hours with the Sweeteners. Samples were collected for 16S sequencing, and for maltitol only, samples were collected for GABA analysis.

[0396] Table 3. Concentration of sweeteners tested in the human gut simulator model.

[0397] Analyzing the Effects of the Sweeteners on the Gut Simulator Model

[0398] DNA extraction was performed using a ZYMOBIOMICS DNA Miniprep Kit. DNA samples were prepared for 16S sequencing using QIASEQPHASED primers (QIAGEN) which target the V3 / V4 region (F: CCTACGGGNGGCWGCAG, SEQ ID NO: 597; R: GACTACHVGGGTATCTAATCC, SEQ ID NO: 598). The samples were sequenced using a V3 MISEQ 600cyc flowcell. The proprietary’ ILLUMINA software Bcl-convert was used to perform quality’ control and adapter trimming and all further processing and analysis was performed in Qiime 2 (Boylcn ct al., 2019). Qiimc2’s cutadapt (Martin, 2011) was used to remove primers and the sequences were then denoised using dada2 (Callahan et al., 2016). Operational taxonomic units (OTUs) were assigned using the Silva 99% OTUs full-length sequences database. The percent relative abundance of Bacteroides and Enterobacteriaceae in each sample was calculated and each ingredient- treated community was compared to the respective donor control community. Statistical significance of Bacteroides and Enterobacteriaceae relative abundance data was calculated using a One-way ANOVA with Dunnett’s multiple comparison test or a Student’s T-test (*p <0.05, ** p <0.01, *** p<0.001, ****p<0.0001) comparing the mean of each ingredient-treated samples to the mean of the donor control samples.

[0399] GABA was quantified by LC / MS. Samples were filter-sterilized using a polyethersulfone (PES) filter. To compare the concentrations of GABA of a single donor’s control communities versus the donor’s communities with maltitol treatment, a Student’s T-test was utilized (*p <0.05, ** p <0.01, *** p<0.001, ****p<0.0001).Results

[0400] An ideal prebiotic candidate sweetener would not lead to growth of Enterobacteriaceae while supporting growth of GABA-producing Bacteroides. To identify these prebiotics, a panel of sweeteners were first tested for their ability to promote growth of Enterobacteriaceae and a GABA producer in monoculture. The results of the monoculture screening are represented in Table 4. D- fructose, mannitol, and D-sorbitol led to the highest levels of growth of Enterobacteriaceae representatives E. colt and S. sonnet, making them poor prebiotic candidates. L-arabinose and L- lyxose supported most of the Enterobacteriaceae representatives to a moderate extent without supporting the representative GABA producer B. xylanisolvens. In addition, L-sorbose, and allulose each supported three of the four Enterobacteriaceae representatives. In contrast, inositol supported just two of the Enterobacteriaceae. Most notably, maltitol was the only sweetener to not support growth of any Enterobacteriaceae representative, yet it supported growth of B. xylanisolvens. These results support maltitol, and to lesser extent inositol, as prebiotic candidates that promote Bacteroides and / or reduce Enterobacteriaceae in the microbiome.

[0401] Table 4. Growth of Enterobacteriaceae strains and a GABA producing Bacteroides on a sweetener panel. Compared to the average of control cultures grown w ithout a sweetener, represents less than 120% of growth, “+” represents between 120.1 %-l 50% of grow th. “++” represents 150. l%-250% of growth, and “+++” represents 250.1% of growth and above.

[0402] Based on the monoculture screening results, the ability of representatives from the sweetener panel to modulate microbiome strains in mixed communities was further assessed in an ex-vivo Human Gut Simulator model (HuGS). A HuGS. a system designed to mimic the human gastrointestinal (GI) tract, offers a controlled environment that permits the study of intricate microbialinteractions in ex- vivo fecal communities without external influences (c.g., genetics, environmental exposures, etc.). In the HuGS, four sweeteners were tested based on the results of the monoculture screen: (1) maltitol and (2) inositol as the most promising prebiotic candidates from the sweetener panel and (3) L-arabinose and (4) L-lyxose as negative controls that broadly supported Enterobacteriaceae without supporting B. xylanisolvens.

[0403] Gut simulator communities were grown with and without the swe...

Claims

CLAIMSWhat is claimed herein is:

1. A prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bacteroides in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase the relative and / or absolute abundance of the at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abrmdance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control.

2. A prebiotic composition for increasing the relative and / or absolute abundance of at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject relative to a control, the prebiotic composition comprising an amount of maltitol effective to increase relative abundance of the at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject relative to a control.

3. A prebiotic composition for decreasing the relative and / or absolute abundance of at least one bacterium of the family Enterobacteriaceae in the gut of a mammalian subject, the prebiotic composition comprising an amount of maltitol effective to decrease the relative and / or absolute abundance of the at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject compared to other formulations containing a sweetener that is not maltitol.

4. The prebiotic composition of any one of claims 1-3, wherein the effective amount of maltitol is comprised by a unit amount of the prebiotic composition.

5. The prebiotic composition of any one of claims 1-4, wherein the effective amount of maltitol is a concentration of at least 1% to at most 100% w / w maltitol.

6. The prebiotic composition of any one of claims 1-5, wherein the effective amount of maltitol is 0.5g to 25g per unit or serving.

7. The prebiotic composition of any one of claims 1-6, wherein the form of maltitol is selected from the group consisting of maltitol syrup, maltitol powder, maltitol crystals, and maltitol gel.

8. The prebiotic composition of claim 7, wherein the maltitol syrup comprises about 5% sorbitol.

9. The prebiotic composition of any one of claims 1-8, wherein at least one maltitol-intcrnalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of die genus Bifidobacteriuminternalizes, is supported by, and / or metabolizes the effective amount of maltitol in the composition in the gut of the mammalian subject.

10. The prebiotic composition of any one of claims 1-9, wherein the mammalian subject is a human.

11. The prebiotic composition of any one of claims 1-10, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject.

12. The prebiotic composition of any one of claims 1-11, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject.

13. The prebiotic composition of any one of claims 1-12, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or scrum, cerebrospinal fluid, breast milk, or fcccs of the mammalian subject.

14. The prebiotic composition of any one of claims 1-13, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves tire mood of the subject.

15. The prebiotic composition of any one of claims 1-14, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.

16. The prebiotic composition of any one of claims 1-15, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absoluteabundance of GABA-producing Bacteroides or the at least one bacterium of the genus Bifidobacterium in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder.

17. The prebiotic composition of claim 16, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR-MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's. Alzheimer's, and Huntington's diseases), orthostatic tremor. Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

18. The prebiotic composition of claim 16 or 17. wherein treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder.

19. The prebiotic composition of claim 18, wherein at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

20. The prebiotic composition of any one of claims 1-19, wherein the prebiotic composition further comprises at least one excipient selected from the group consisting of encapsulation materials (e.g., chitosan, wax, and gelatin), solubilizers (e.g., TWEEN 80 or SPAN 60), bulking agents (e.g., maltodextrin or microci stalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g.. ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof.

21. The prebiotic composition of any one of claims 1-20, wherein the prebiotic composition further comprises at least one additional prebiotic selected from the group consisting of amino acid (e.g., arginine, glutarate, and ornithine), biotin, fructooligosaccharide, galactooligosaccharide, hemi cellulose (e.g.. arabinoxylan, xylan. xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, gum (e.g., guar gum, gum arabic, and carrageenan), oligofructose, oligodextrose, tagatose. resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide. pectin (e.g.. xylogalactouronan, citrus pectin, apple pectin, andrliamnogalacturonan-I), dietary fiber (c.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccharide, and polyamine (e.g., spermidine, putrescine).

22. The prebiotic composition of any one of claims 1-21, wherein the prebiotic composition is formulated for delivery to the gut of a mammalian subject.

23. The prebiotic composition of any one of claims 1-22, wherein the prebiotic composition is in the form of a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a candy, a syrup, an elixir, a lozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

24. The prebiotic composition of any one of claims 3-23, wherein the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence selected from Table 7.

25. The prebiotic composition of any one of claims 3-24, wherein the at least one bacterium of the family Enterobacteriaceae comprises a 16S sequence comprising one of SEQ ID NOs: 46-89 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 46-89.

26. The prebiotic composition of any one of claims 3-25, wherein the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8.

1. The prebiotic composition of any one of claims 3-26. wherein the at least one bacterium of the family Enterobacteriaceae comprises a genome selected from Table 8 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 8.

28. The prebiotic composition of any one of claims 1-27, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium selected from the “increased” column ofTable 11.

29. The prebiotic composition of any one of claims 1-28, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence selected from Table 12.

30. The prebiotic composition of any one of claims 1-29, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence comprising one of SEQ ID NOs: 207-360 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 207-360.

31. The prebiotic composition of any one of claims 1-30, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 13.

32. The prebiotic composition of any one of claims 1-31, wherein the prebiotic increases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table I 3or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 13.

33. The prebiotic composition of any one of claims 1-32, wherein the prebiotic increases the relative and / or absolute abundance of a combination of bacteria selected from Table 16.

34. The prcbiotic composition of any one of claims 1-33, wherein the prcbiotic decreases the relative and / or absolute abundance of at least one bacterium selected from the “decreased” column of Table 11.

35. The prebiotic composition of any one of claims 1-34, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence selected from Table 14.

36. The prebiotic composition of any one of claims 1-35, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a 16S sequence comprising one of SEQ ID NOs: 361-596 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 361-596.

37. The prebiotic composition of any one of claims 1-36, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 15.

38. The prebiotic composition of any one of claims 1-37, wherein the prebiotic decreases the relative and / or absolute abundance of at least one bacterium comprising a genome selected from Table 15or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 15.

39. A synbiotic composition comprising the prebiotic composition of any one of claims 1-38 and at least one bacterial species.

40. A synbiotic composition comprising maltitol and at least one bacterial species.

41. The synbiotic composition of any one of claims 39-40, wherein the synbiotic composition comprises an amount of maltitol effective to increase the growth rate and / or metabolic activity’ of at least one bacterium of the genus Bacteroides in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by the mammalian subject.

42. The synbiotic composition of any one of claims 39-41, wherein the synbiotic composition comprises an amount of maltitol effective to increase the growth rate and / or metabolic activity of at least one bacterium of the genus Bifidobacterium in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is increased when the prebiotic composition is consumed by tire mammalian subject.

43. The synbiotic composition of any one of claims 39-42. wherein the synbiotic composition comprises an amount of maltitol effective to decrease the growth rate and / or metabolic activity of at least one bacterium of the family Enterobacteriaceae in the gut of the mammalian subject, such that the relative and / or absolute abundance of such bacterium in the gut of the mammalian subject is decreased when the prebiotic composition is consumed by the mammalian subject.

44. The synbiotic composition of any one of claims 39-43. wherein the effective amount of maltitol is comprised by a unit amount of the synbiotic composition.

45. The synbiotic composition of any one of claims 39-44, wherein the effective amount of maltitol is a concentration of at least 1% to at most 100% w / w maltitol.

46. The synbiotic composition of any one of claims 39-45, wherein the at least one bacterial species is at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species encodes and / or expresses a protein or protein complex that internalizes and / or metabolizes maltitol.

47. The synbiotic composition of any one of claims 39-46. wherein the protein or protein complex that internalizes and / or metabolizes maltitol is selected from Table 9 or Table 10.

48. The synbiotic composition of any one of claims 39-47. wherein the protein or protein complex that internalizes and / or metabolizes maltitol is maltitol dehydrogenase or a-glucosidase.

49. The synbiotic composition of any one of claims 39-48. wherein the protein or protein complex that internalizes maltitol comprises one of SEQ ID NOs: 171-206 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 171-206 that maintains its function as a polypeptide.

50. The synbiotic composition of any one of claims 39-49, wherein the protein or protein complex that metabolizes maltitol comprises one of SEQ ID NOs: 90-170 or an amino acid sequence that is at least 95% identical to one of SEQ ID NOs: 90-170 that maintains its function as a polypeptide.

51. The synbiotic composition of any one of claims 39-50, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence selected from Table 5 or Table 12.

52. The synbiotic composition of any one of claims 39-51, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or 207-360 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 1-45 or 207-360.

53. The synbiotic composition of any one of claims 39-52, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 6 or Table 13.

54. The synbiotic composition of any one of claims 39-53, wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a genome selected from Table 6 or Table 13 or a nucleic acid sequence that is at least 95% identical a genome selected from Table 6 or Table 13.

55. The synbiotic composition of any one of claims 39-54. wherein the at least one maltitol- internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species comprises a combination of bacteria selected from Table 16.

56. The synbiotic composition of any one of claims 39-55, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is dried and / or viable.

57. The synbiotic composition of any one of claims 39-56, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is freeze- dried and / or spray -dried.

58. The synbiotic composition of any one of claims 39-57. wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is a viable, isolated bacterial species.

59. The synbiotic composition of any one of claims 39-58. wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is present at a concentration of at a concentration of at least 101colony forming units per gram (CFU / g) to at most 1013CFU / g.

60. The synbiotic composition of any one of claims 39-59, wherein the at least one maltitol- intemalizing. and / or maltitol-metabolizing, and / or maltitol-supported bacterial species is at least one bacterium of the genus Bacteroides.61 . The synbiotic composition of any one of claims 39-60, wherein the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifaciens, B. caccae, B. caecicola, B. caecigallinarum, B. cellulosilyticus, B. cellulosolvens. B. clams, B. coagulans, B. coprocola. B. coprophilus, B. coprosuis, B. dorei, B. eggerthii, B. faecichinchillae, B. faecis, B. finegoldii, B. fluxus, B. fragilis, B. galacturonicus, B. gallinaceum, B. gallinarum, B. goldsteinii, B. gramini solvens, B. helcogene, B. intestinalis, B. luti, B. massiliensis, B. nordii, B. oleiciplenus, B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifaciens, B. putredinis, B. pyogenes, B. reticulotermitis, B. rodentium, B. salanitronis, B. salyersiae, B. sartorii, B. stercoris, B. thetaiotaomicron, B. uniformis, B. vulgatus, and B. xylanisolvens.

62. The synbiotic composition of any one of claims 39-61, wherein the at least one bacterium of the genus Bacteroides comprises a 16S sequence comprising one of SEQ ID NOs: 1-45 or a nucleic acid sequence that is at least 95% identical to one of SEQ ID NOs: 1-45.

63. The synbiotic composition of any one of claims 39-62. wherein the at least one bacterium of the genus Bacteroides comprises a genome selected from Table 6 or a nucleic acid sequence that is at least 95% identical to a genome selected from Table 6.

64. The synbiotic composition of any one of claims 39-63. wherein the at least one bacterium of the genus Bacteroides encodes and expresses a protein or protein complex that internalizes and / or metabolizes maltitol.

65. The synbiotic composition of any one of claims 39-64. wherein the protein or protein complex that internalizes and / or metabolizes maltitol comprises one of SEQ ID NOs: 179-295 or an aminoacid sequence that is at least 95% identical to one of SEQ ID NOs: 179-295 that maintains its function as a polypeptide.

66. The synbiotic composition of any one of claims 39-65, wherein the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides internalizes and / or metabolizes tire maltitol in the composition in the gut of a mammalian subject.

67. The synbiotic composition of any one of claims 39-66. wherein die mammalian subject is a human.

68. The synbiotic composition of any one of claims 39-67. wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol- intemalizing. and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides by at least 1% in the gut of the mammalian subject.

69. The synbiotic composition of any one of claims 39-68, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.

70. The synbiotic composition of any one of claims 39-69, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases die concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.

71. The synbiotic composition of any one of claims 39-70. wherein die increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or semm, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject.

72. The synbiotic composition of any one of claims 39-71. wherein die increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum.cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.

73. The synbiotic composition of any one of claims 39-72, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) and / or the relative and / or absolute abundance of GABA-producing Bacleroides in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject is used for treating or improving symptoms of a mental disease or disorder.

74. The synbiotic composition of claim 39-73, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR-MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiff-person syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

75. The synbiotic composition of claim 73 or 74, wherein treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder.

76. The synbiotic composition of claim 75, wherein at least one symptom of the mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability’, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memory loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

77. The synbiotic composition of any one of claims 39-76, wherein the synbiotic composition further comprises at least one excipient selected from the group consisting of encapsulation materials (e.g., chitosan, wax, and gelatin), solubilizers (e.g., Tween 80 or Span 60), bulking agents (e.g., maltodextrin or microcry stalline cellulose), binders (e.g., cellulose derivatives or gums), preservatives (e.g.. ascorbic acid or sodium benzoate), food colorings, and antioxidants, or a combination thereof.

78. The synbiotic composition of any one of claims 39-77. wherein the synbiotic composition further comprises at least one additional prebiotic selected from the group consisting of amino acid (e.g., arginine, glutarate, and ornithine), biotin, fructooligosaccharide, galactooligosaccharide, hemicellulose (e.g., arabinoxylan, xylan, xyloglucan, glucomannan), inulin, chitin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, gum (e.g., guar gum, gum arabic, and carrageenan), oligofructose, oligodextrose, tagatose, resistant maltodextrins (e.g., resistant starch), trans-galactooligosaccharide, pectin (e.g., xylogalactouronan, citrus pectin, apple pectin, and rhamnogalacturonan-I), dietary fiber (e.g., soy fiber, sugarbeet fiber, pea fiber, com bran, and oat fiber), xylooligosaccharide, and polyamine (e.g., spermidine, putrescine).

79. The synbiotic composition of any one of claims 39-78. wherein the synbiotic composition is formulated for delivery to the gut of a mammalian subject.

80. The synbiotic composition of any one of claims 39-79. wherein the synbiotic composition is in the form of a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

81. A nutritional supplement comprising the prebiotic composition of any one of claims 1-38 or the synbiotic composition of any one of claims 39-80.

82. The nutritional supplement of claim 81, wherein the prebiotic composition or the synbiotic composition is at a concentration of at least 1% to at most 70% in the nutritional supplement.

83. The nutritional supplement of any one of claims 81-82. wherein the nutritional supplement is formulated for delivery' to the gut of a mammalian subject.

84. The nutritional supplement of any one of claims 81-83. wherein the nutritional supplement is in the form of a probiotic, a prebiotic, a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a candy, a syrup, an elixir, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

85. A food composition comprising the prebiotic composition of any one of claims 1-38 or the synbiotic composition of any one of claims 39-80.

86. The food composition of claim 85, wherein the food composition is selected from the group consisting of milk, yogurt, plant-based dairy alternatives (e.g., oat milk, almond milk, coconut milk, soy milk, pea milk, etc.), soft drinks (e.g., soda, carbonated water, etc.) fermented milk, protein shakes, fruit juice (e.g., apple juice, orange juice, grapefruit juice, grape juice, etc.), nondairy fermented beverages (e.g., kombucha, etc.), vegetable juices (e.g. carrot juice, tomato juice, etc.), alcoholic beverages (e.g., camred cocktail, alcoholic cider, etc.), sauces (e.g., gravy, tomato sauce, barbeque sauce, etc.), broth and stock (e.g., chicken stock, beef broth, vegetable broth, etc.), syrups, tea beverages (e.g., tea-based powder, milk tea, etc.), coffee beverages (e.g., cold brew, latte, iced coffee), yogurt beverages, or cereal-based beverages (e.g., rice milk, beer, barley tea, etc.).

87. The food composition of any one of claims 85-86. wherein the food composition is selected from the group consisting of granola bars, meal replacement bars, protein bars, fruit bars, breakfastcereals, pastas, bread products (c.g., loaves, buns, croutons, etc.), condiments and relishes (c.g., ketchup, relish, etc.), frosting, gelatin and pudding, cough drops, or jams and jellies.

88. The food composition of any one of claims 85-87, wherein the food composition is selected from the group of food concentrates consisting of bouillon concentrate, soup concentrate, or gravy concentrate.

89. The food composition of any one of claims 85-88, wherein the food composition is a confectionary selected from the group consisting of a chocolate composition, a chocolate analogue composition, chewing gum, soft chew candy, gummy candy, or hard candy.

90. The food composition of any one of claims 85-89. wherein the food composition is a frozen confection (e.g., ice cream, sorbet, sherbet, frozen yogurt or water ice), is a frozen confection product comprising a frozen composition and a chocolate composition or a chocolate analogue composition wherein the chocolate composition or a chocolate analogue composition is in the form of a coating on the frozen composition and / or inclusions located within the frozen composition and / or a ripple or swirl of sauce.

91. The food composition of any one of claims 85-90, wherein the prebiotic composition or the symbiotic composition is at a concentration of at least 1% to at most 70% in the food composition.

92. A medical food for the improvement of mood, the promotion of relaxation, the promotion of a calming mood state, and / or the treatment of depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, comprising an effective amount of maltitol, wherein the medical food is formulated to provide a daily dosage of maltitol in the effective amount of 0.5g to 25g based on a serving size of about 0.8g to 125g of said medical food taken up to three times a day.

93. A medical food for the improvement of mood, the promotion of relaxation, the promotion of a calming mood state, and / or the treatment of depression, anxiety', stress, and / or other mental health disorders in a mammalian subject in need thereof, comprising an effective amount of maltitol and at least one bacterial species, wherein the medical food is formulated to provide (a) a daily dosage of maltitol in the effective amount of 0.5 g to 25 g and (b) a daily dosage of the at least one bacterial species of 101CFU / g to 1013CFU / g, based on a serving size of about 0.8g to 125 g of said medical food taken up to three times a day.

94. The use of maltitol in the food composition of any one of claims 85-91 or in the medical food of any one of claims 92-93 for replacing sugar in the food composition or in the medical food.

95. A pharmaceutical composition comprising the prebiotic composition of any one of claims 1-38 or the synbiotic composition of any one of claims 39-80, and a pharmaceutically acceptable carrier.

96. The pharmaceutical composition of claim 95, wherein the prebiotic composition or the synbiotic composition is at a concentration of at least 1% to at most 70% in the pharmaceutical composition.

97. The pharmaceutical composition of any one of claims 95-96, wherein the pharmaceutical composition is formulated for delivery' to the gut of a mammalian subject.

98. The pharmaceutical composition of any one of claims 95-97, wherein the pharmaceutical composition is in the form of a probiotic, a prebiotic, a synbiotic, a capsule, a tablet, a caplet, a pill, a troche, a lozenge, a powder, a granule, a medical food, a supplement, a gummy, a gel, a sachet, or a combination thereof.

99. The use of maltitol in the preparation of a medicament for the treatment of a disease or disorder related to low or reduced GABA levels.

100. The use of claim 99, wherein the disease or disorder related to low or reduced GABA levels is a mental disease or disorder.

101. The use of claim 100, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiffperson syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

102. A method of improving mood in a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98.

103. A method of promoting relaxation and / or promoting a calming mood state in a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80. the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98.

104. A method of reducing stress or anxiety in a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80. the nutritional supplement of any one of claims81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98.

105. A method of increasing the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one maltitol-intemalizing, and / or maltitol- metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80. the nutritional supplement of any one of claims 81-84. the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98.

106. A method of increasing the production rate of y-aminobutyric acid (GABA) by at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides in the gut of a mammalian subject or at least one bacterium of the genus Bifidobacterium, and / or increasing the concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a mammalian subject, the method comprising administering an effective amount of the prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85- 91, the medical food of any one of claims 92-93. or the pharmaceutical composition of any one of claims 95-98.

107. A method of treating depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof, the method comprising administering an effective amount of the prebiotic composition of any one of claims 1-38, die sy nbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98.

108. The method of any one of claims 102-107, wherein tire mammalian subject is a human.

109. The method of any one of claims 102-108, wherein tire administering is to the gut of the subject.

110. The method of any one of claims 102-109, wherein improving mood in the mammalian subject, promoting relaxation and / or promoting a calming mood state in the mammalian subject, and / or reducing stress and / or anxiety in the mammalian subject is measured by a test selected from the group consisting of the Hopkins Symptom Checklist-25, Hamilton Depression Rating Scale, the Beck Depression Inventory, Positive and Negative Affect Schedule, Profile of Mood states (POMS) Questionnaire, a friendliness score. General Anxiety Disorder Questionnaire-7(GAD-7), Visual Analog Mood Scale, VAS / Likert Seale, Perceived Stress Seale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Center for Epidemiologic Studies Depression Scale, Geriatric Depression Scale, Montgomer -Asberg Depression Rating Scale, Cohen’s Perceived Stress Scale. Holmes and Rahe Stress Scale, World Health Organization Quality of Life, Short Form Health Survey (SF-36), and EuroQol five dimensions questiomiaire, or a combination thereof.

111. The method of any one of claims 102-110, wherein mood is improved in the subject by at least 5%.

112. The method of any one of claims 102-111, wherein relaxation is promoted in the subject by at least 5%.

113. The method of any one of claims 102-112, wherein a calming mood state is promoted in the subject by at least 5%.

114. The method of any one of claims 102-113, wherein stress and / or anxiety is reduced in the subject by at least 5%.

115. The method of any one of claims 102-114. wherein at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium internalizes and / or metabolizes and / or is supported by maltitol from the composition in the gut of the mammalian subject.

116. The method of any one of claims 102-115. wherein the internalization and / or metabolization by or the support of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of tire effective amount of maltitol increases the relative and / or absolute abundance of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium by at least 1% in the gut of the mammalian subject.

117. The method of any one of claims 102-116, wherein the increase of the relative and / or absolute abundance of the at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol- supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium is determined by:(i) quantifying the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject before ingestion of the composition;(ii) quantifying the at least one maltitol-intcrnalizing, and / or maltitol-mctabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium in a fecal sample collected from the subject after ingestion of the composition;(iii) and determining the relative and / or absolute abundance of the at least one maltitol- intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or the at least one bacterium of the genus Bacteroides or the at least one bacterium of the genus Bifidobacterium from the data from (ii) compared to the data from (i).

118. The method of claim 117, wherein quantification of (i) and / or (ii) comprises nucleic acid sequencing.

119. The method of claim 118, wherein the nucleic acid sequencing comprises 16S metagenomic sequencing, shotgun metagenomic sequencing, and / or amplification and sequencing of the 16S gene by polymerase chain reaction and sequencing.

120. The method of claim 117, wherein quantification of (i) and / or (ii) comprises non-sequencing- based methods.

121. The method of any one of claims 102-120. wherein the at least one bacterium of the genus Bacteroides is selected from the group consisting of B. acidifaciens. B. caccae, B. caecicola, B. caecigallmarum. B. cellulosilyticus. B. celhtlosolvens, B. clarus, B. coagulans, B. coprocola, B. coprophilus, B. coprosuis, B. dorei, B. eggerthii. B. faecichinchillae, B. faecis. B. finegoldii, B. fluxus. B. fragilis, B. galacturonicus, B. gallinaceum, B. gallinarum, B. goldsteinii, B. graminisolvens, B. helcogene, B. intestinalis, B. luti, B. massiliensis, B. nordii, B. oleiciplenus, B. oris, B. ovatus, B. paurosaccharolyticus, B. plebeius, B. propionicifaciens, B. putredinis. B. pyogenes, B. reticulotermitis, B. rodentium, B. salanitronis, B. salyersiae, B. sartorii, B. stercoris, B. thetaiotaomicron, B. uniformis, B. vulgatus, and B. xylanisolvens.

122. The method of any one of claims 102-121, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitol increases the production of y-aminobutyric acid (GABA) by the at least one maltitol-internalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.

123. The method of any one of claims 102-122, wherein the internalization and / or metabolization by or the support of the at least one maltitol-intemalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or by the at least one bacterium of the genus Bacteroides or by the at least one bacterium of the genus Bifidobacterium of the effective amount of maltitolincreases the concentration of y-aminobutyric acid (GABA) by at least 1% in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject.

124. The method of any one of claims 102-123, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject improves the mood of the subject.

125. The method of any one of claims 102-124, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) in the gut, blood plasma or serum, cerebrospinal fluid, breast milk, or feces of the mammalian subject reduces stress and / or anxiety in the subject.

126. The method of any one of claims 102-125, wherein the increased production rate and / or concentration of y-aminobutyric acid (GABA) treats or improves symptoms of a mental disease or disorder.

127. The method of claim 126, wherein the mental disease or disorder is selected from the group consisting of depression, bipolar disorder, schizophrenia, anxiety, anxiety disorders, obsessive compulsive disorder, eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant / restrictive food intake disorder, other specified feeding or eating disorder, pica, and rumination disorder), addiction, social phobia, treatment-resistant major depressive disorder (TR- MDD), major depressive disorder and its subtypes (melancholic depression, atypical depression, catatonic depression, postpartum depression, and seasonal affective disorder), neurodegenerative amyloid disorders (Parkinson's, Alzheimer's, and Huntington's diseases), orthostatic tremor, Lafora disease, restless leg syndrome, neuropathic pain, pain disorders, dementia, epilepsy, stiffperson syndrome, premenstrual dysphoric disorder, autism spectrum disorder, sleep disorders, and attention deficit hyperactivity disorder (ADHD), and combinations thereof.

128. The method of claim 126 or 127, wherein treating or improving the mental disease or disorder comprises decreasing at least one symptom of the mental disease or disorder.

129. The method of claim 128, wherein at least one symptom of tire mental disease or disorder is selected from the group consisting of fatigue, insomnia, motor dysfunction, stress, persistent anxiety, persistent sadness, social withdrawal, substance withdrawal, irritability, thoughts of suicide, thoughts of self-harm, restlessness, low sex drive, lack of focus, seizures, memoty loss, anger, bouts of emotional reactivity, confusion, pain, and muscle spasms, loss of appetite, altered intestinal motility, quality of life score, and combinations thereof.

130. The method of any one of claims 102-129, wherein the method further comprises administering at least one mood-improving therapeutic to the subject.

131. The method of any one of claims 102-130, wherein the method further comprises administering at least one anti-depression, anti-anxiety, and / or anti-stress therapeutic to the subject.

132. The method of any one of claims 102-131, wherein the method further comprises identifying a subject in need of treatment by determining whether the subject would benefit from an increase in endogenous GABA and / or GABA-producing bacteria by measuring an initial amount of GABA in the subject's stool.

133. The method of claim 132, wherein the initial amount of endogenous GABA in the subject's stool is below about 300 pg per gram (pg / g), about 200 pg / g. about 100 pg / g, about 50 pg / g, about 20 pg / g. or about 10 pg / g of wet or dry stool.

134. The method of claim 132 or 133, wherein the amount of GABA in the subject's stool is increased relative to the initial amount after administering the maltitol formulation.

135. The method of any one of claims 102-134, wherein the method further comprises identifying a subject in need of treatment by determining whether the subject would benefit from an increase in endogenous GABA by measuring an initial amount of GABA-producing bacteria in the subject's stool.

136. The method of claim 135, wherein the initial amount of GABA-producing bacteria in the subject's stool is less than about 50%, about 40%, about 30%. about 20%, about 10%, about 5%, or about 1% of total bacteria as measured by 16S sequence mapping.

137. The method of claim 135 or 136, wherein the amount of GABA-producing bacteria in the subject's stool is increased relative to the initial amount after administering the maltitol formulation.

138. The method of any one of claims 135-137. wherein the GABA-producing bacteria are selected from Table 5, Table 6, Table 11 (e.g., “increased” column), Table 12, or Table 13.

139. The method of any one of claims 135-138, wherein the GABA-producing bacteria encode or express a protein or protein complex that internalizes and / or metabolizes maltitol selected from Table 9 or Table 10.

140. The method of any one of claims 135-139, wherein the GABA-producing bacteria comprise at least one bacterium of the genus Bacteroides.

141. The prebio tic composition of any one of claims 1-38, wherein the prebiotic composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the prebiotic composition is for the use of any one of claims 102-140.

142. The synbiotic composition of any one of claims 39-80. wherein the symbiotic composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the synbiotic composition is for the use of any one of claims 102-140.

143. The nutritional supplement of any one of claims 81-84, wherein the nutritional supplement is comprised by a packaged food product, wherein the package of the packaged food product isassociated with or comprises indicia that the nutritional supplement is for the use of any one of claims 102-140.

144. The food composition of any one of claims 85-91, wherein the food composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the food composition is for the use of any one of claims 102-140.

145. The medical food of any one of claims 92-93, wherein the medical food is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the medical food is for the use of any one of claims 102-140.

146. The pharmaceutical composition of any one of claims 95-98. wherein the pharmaceutical composition is comprised by a packaged food product, wherein the package of the packaged food product is associated with or comprises indicia that the pharmaceutical composition is for the use of any one of claims 102-140.

147. The prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84. the food composition of any one of claims 85-91, the medical food of any one of claims 92-93. or the pharmaceutical composition of any one of claims 95-98 for use in a method of improving mood in a mammalian subject.

148. The prebiotic composition of any one of claims 1-38. the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98 for use in a method of promoting relaxation and / or promoting a calming mood state in a mammalian subject.

149. The prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98 for use in a method of reducing stress or anxiety in a mammalian subject.

150. The prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmacal composition of any one of claims 95-98 for use in a method of increasing the relative abundance, absolute abundance, growth rate, metabolic activity, proportion, and / or concentration of at least one maltitol-internalizing, and / or maltitol-metabolizing, and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject.

151. The prebio tic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91, the medical food of any one of claims 92-93, or the pharmaceutical composition of any one of claims 95-98 for use in a method of increasing the production rate of y- aminobutyric acid (GABA) by at least one maltitol-intemalizing, and / or maltitol-metabolizing. and / or maltitol-supported bacterial species or at least one bacterium of the genus Bacteroides or at least one bacterium of the genus Bifidobacterium in the gut of a mammalian subject, and / or increasing the concentration of y-aminobutyric acid (GABA) in the gut. blood plasma or serum, cerebrospinal fluid, breast milk, or feces of a mammalian subject.

152. The prebiotic composition of any one of claims 1-38, the synbiotic composition of any one of claims 39-80, the nutritional supplement of any one of claims 81-84, the food composition of any one of claims 85-91. the medical food of any one of claims 92-93, or the pharmacal composition of any one of claims 95-98 for use in a method of treating depression, anxiety, stress, and / or other mental health disorders in a mammalian subject in need thereof.

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