Synbiotic compositions for gut dysbiosis

Abstract

Synbiotic compositions comprising, consisting of, or consisting essentially of, one or more prebiotics and one or more probiotics are provided. Such compositions may be used to treat gut dysbiosis and / or to ameliorate one or more symptoms associated therewith.

Description

[0001] SYNBIOTIC COMPOSITIONS FOR GUT DYSBIOSIS

[0002] FIELD

[0003] The present disclosure generally relates to the dietary supplements comprising one or more prebiotics and one or more probiotics. More specifically, the present disclosure relates to dietary supplement compositions that may reduce gut dysbiosis and / or leaky gut, and that may be useful in the treatment and / or management of one or more disorders relating to the gut.

[0004] BACKGROUND

[0005] Microbial dysbiosis of the gut is an imbalance in the gut microbiome that may lead to a loss of beneficial microorganisms, an overgrowth of harmful ones, and / or a loss of overall microbial diversity. This imbalance can disrupt normal gut functions and is linked to various health issues, including digestive problems like diarrhea and constipation, inflammatory bowel disease (IBD), metabolic disorders, and even neurological conditions through the gutbrain axis.

[0006] While its exact etiology can vary from person to person, microbial dysbiosis can arise in an individual for one or more of several reasons. For example, a diet low in fiber and high in processed foods, sugar, and saturated fats can contribute to dysbiosis. Bacterial, viral, or parasitic infections can trigger dysbiosis. Antibiotics in particular can reduce both harmful and beneficial bacteria. Stress, lack of sleep, and other lifestyle factors can impact the gut microbiome. As may be expected, any combination of the foregoing can also cause, or contribute to, microbial dysbiosis in an individual.

[0007] As with etiology, symptoms of microbial dysbiosis can vary widely from person to person, with specific symptoms often depending on the specific imbalance. Common symptoms include nausea, bloating and gas, diarrhea or constipation, stomach pain or upset stomach, fatigue, anxiety or depression, and skin rashes, among other symptoms.

[0008] The potential health consequences of microbial dysbiosis are numerous and varied and microbial dysbiosis of the gut is implicated in numerous conditions, as described hereinbelow. For example, dysbiosis is implicated in inflammatory bowel diseases (IBD) like Crohn's and ulcerative colitis, as well as irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). It is also linked to conditions like obesity and metabolic syndrome, it can contribute to autoimmune diseases and influence immune function, and it has been linked to fatigue, anxiety, and depression because the gut-brain axis connects the gut microbiome to the brain.

[0009] SUMMARY

[0010] Consequently, there is a need to for novel dietary supplement compositions that may reduce gut dysbiosis and leaky gut, and that may be useful in the treatment and / or management of one or more disorders relating to the gut. The present disclosure provides such compositions and related benefits as well. Generally speaking, the present disclosure provides synbiotic compositions, meaning that the disclosed compositions are combinations of prebiotic and probiotic components. In this regard, the disclosed synbiotic compositions provide both one or more probiotic microbes in combination with one or more nutrients needed for those probiotic microbes to live and grow.

[0011] In a first aspect, the present disclosure provides compositions for enhancing gut health and alleviating symptoms associated with gut dysbiosis, such compositions comprising one or more prebiotics and one or more probiotics. Generally speaking, the combined prebiotics and probiotics in the disclosed compositions can work synergistically to promote a balanced gut microbiota and enhance overall immune function.

[0012] In embodiments, the prebiotic comprises one or more prebiotics selected from the group consisting of Acai berries, Acai berry powder, Acai berry extract, Acacia fiber, Acerola cherry powder, Acerola cherry extract, Agave inulin, Almond butter, Almond powder, Almond extract, Almonds, Amla powder, Amla extract, Apple pectin, Apple powder, Apple extract, Arabinogalactan, Artichoke extract, Artichokes, Ashwagandha powder, Ashwagandha extract, Asparagus, Bacillus coagulans, Bamboo shoots, Banana powder, Banana extract, Bananas, Baobab powder, Baobab extract, Barley, Beans, Beets, Benecaries, Berries, Beta-glucan, Betel nut powder, Betel nut extract, Bilberries, Bilberry powder, Bilberry extract, Black currant powder, Black currant extract, Black currants, Blackberries, Blackberry powder, Blackberry extract, Blueberries, Blueberry powder, Blueberry extract, Brazil nut butter, Brazil nut powder, Brazil nut extract, Broccoli, Broccoli powder, Broccoli extract, Burdock root, Burdock root extract, Butternut powder, Butternut extract, Cacao butter, Cacao powder, Cacao extract, Cacao nibs, Cashew butter, Cashew powder, Cashew extract, Cashews, Celeriac, Celery, Cellulose, Cherries, Cherry extract, Cherry powder, Chia seeds, Chicory root, Chicory root extract, Citrus fruits, Citrus pectin, Citrus extract, Coconut butter, Coconut powder, Coconut extract, Coconut water, Coconuts, Coffee cherry powder, Coffee cherry extract, Cranberries, Cranberry powder, Cranberry extract, Dandelion greens, Dandelion extract, Date powder, Date extract, Dates, Elderberries, Elderberry powder, Elderberry extract, Fennel, Fennel extract, Fenugreek, Fenugreek extract, Flaxseeds, Flaxseed extract, Fructooligosaccharides (FOS), Galactomannans, Galactooligosaccharides (GOS), Garlic, Garlic, Garlic extract, Glucomannan, Goji berries, Goji berry powder, Goji berry extract, Grape powder, Grape extract, Grapes, Grapefruit, Grapefruit pectin, Grapefruit extract, Green peas, Green tea, Green tea powder, Green tea extract, Guar gum, Partially hydrolyzed guar gum, Guava, Guava powder, Guava extract, Hazelnut, Hazelnut butter, Hazelnut powder, Hazelnut extract, Hazelnuts, Honey, Human milk oligosaccharides (HMO), Inulin, Isomaltooligosaccharides (IMO), Jerusalem artichoke, Jerusalem artichoke extract, Kale, Kale powder, Kale extract, Karaya gum, Kefir, Kiwi, Kiwi powder, Kiwi extract, Kombucha, Konjac root, Konjac root extract, Lactulose, Lentils, Leeks, Locust bean gum, Macadamia nut butter, Macadamia nut powder, Macadamia nut extract, Macadamia nuts, Maqui berry powder, Maqui berry extract, Matcha powder, Matcha extract, Milk, Mulberry powder, Mulberry extract, Mushrooms, Oat bran, Oats, Okra, Onion powder, Onion extract, Onions, Orange powder, Orange extract, Oranges, Pecan butter, Pecan powder, Pecan extract, Pecans, Pectin, Papaya powder, Papaya extract, Papayas, Parsley, Pecan nut butter, Pectin, Peas, Pineapple powder, Pineapple extract, Pineapples, Pistachio butter, Pistachio powder, Pistachio extract, Pistachios, Plantain, Pomegranate powder, Pomegranate extract, Pomegranates, Potato startch, Psyllium husk, Pumpkin, Pumpkin powder, Pumpkin extract, Pumpkin seeds, Radish, Raffinose, Rhubarb, Rhubarb extract, Rye, Salsify, Sauerkraut, Shallots, Soybeans, Spinach, Spinach powder, Spinach extract, Stachyose, Starch, Strawberries, Strawberry powder, Strawberry extract, Sunflower seeds, Sweet potatoes, Tamarind gum, Tamarind extract, Turmeric powder, Turmeric extract, Turnips, Verbascose, Walnut butter, Walnut powder, Walnut extract, Walnuts, Wheat bran, Whole wheat bread, Xanthan gum, Xylooligosaccharides (XOS), Yacon syrup, Yeast beta-glucan, Yogurt, or combinations thereof.

[0013] In some embodiments, the prebiotic is an ingredient suitable to supplement a population of Faecalibacterium prausnitzii (F. prausnitzii). In some embodiments, the prebiotic is low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP). In some embodiments, the prebiotic is kiwi powder; in some embodiments, the prebiotic is walnut powder; and in some embodiments the prebiotic is a combination of kiwi powder and walnut powder. In some embodiments, the prebiotic is partially hydrolysed guar gum (PHGG).

[0014] In some embodiments, the prebiotic in the disclosed compositions is kiwi powder and the amount provided in the composition is suitable to supplement the population of F. prausnitzii. In some embodiments, the prebiotic supplements the population of Roseburia hominis.

[0015] In any of the foregoing embodiments, the prebiotic components, one or more of which may be low FODMAP, minimize gastrointestinal discomfort such as gas and bloating.

[0016] In embodiments, the probiotic is one or more bacteria selected from the group consisting of Anaerostipes caccae, Anaerostipes hadrus, Aspergillus niger, Aspergillus oryzae, Bacillus clausii, Bacillus coagulans, Bacillus licheniformis, Bacillus subtilis, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium intestinalis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium scardovii, Blautia hansenii, Blautia luti, Blautia obeum, Blautia producta, Blautia schitovskii, Blautia wexlerae, Butyrivibrio alvinus, Butyrivibrio crossotus, Butyrivibrio fibrisolvens, Butyrivibrio hungatei, Butyrivibrio lipocalidus, Butyrivibrio matronii, Butyrivibrio parvus, Butyrivibrio phytoremedians, Butyrivibrio plebeius, Butyrivibrio proteoclasticus, Butyrivibrio pseudofibrisolvens, Butyrivibrio straminisolvens, Butyrivibrio vermis, Butyrivibrio xylanivorans, Clostridium butyricum, Clostridium perfringens, Coprococcus catus, Coprococcus comes, Enterococcus faecalis, Enterococcus faecium, Escherichia coli (E. coli), Eubacterium biforme, Eubacterium brachy, Eubacterium cellulosolvens, Eubacterium combesii, Eubacterium coprostanoligenes, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium eligens, Eubacterium hallii, Eubacterium hadrum, Eubacterium incestum, Eubacterium limosum, Eubacterium minutum, Eubacterium multiforme, Eubacterium nitritogenes, Eubacterium nodatum, Eubacterium pexum, Eubacterium rectale, Eubacterium ruminantium, Eubacterium saburreum, Eubacterium siraeum, Eubacterium tenue, Eubacterium tortuosum, Eubacterium uniforme, Eubacterium ventriosum, Eubacterium xylanophilum Faecalibacterium prausnitzii, Faecalibacterium pseudoprausnitzii, Lactobacillus acidophilus, Lactobacillus agilis, Lactobacillus alimentarius, Lactobacillus aviarius, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus gallinarum, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus lactis, Lactobacillus mucosae, Lactobacillus panis, Lactobacillus pentosus, Lactobacillus plantarum, Lactobacillus psittaci, Lactobacillus pullorum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus ruminis, Lactobacillus saerimneri, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus sharpeae, Lactobacillus suebicus, Lactococcus cremoris, Lactococcus lactis, Leuconostoc lactis, Leuconostoc mesenteroides, Megasphaera elsdenii, Mitsuokella jalaludinii, Odoribacter splanchnicus, Pediococcus acidilactici, Pediococcus pentosaceus, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Saccharomyces boulardii, Saccharomyces cerevisiae, Streptococcus thermophilus, or combinations thereof.

[0017] In some embodiments, the disclosed compositions are low histamine-producing probiotic blends that include Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, or Lactobacillus rhamnosus individually or in any combination thereof.

[0018] In some embodiments, the disclosed compositions comprise probiotic bacteria selected from Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium longum, or any combination of the foregoing. In some embodiments, the disclosed compositions may further comprise butyrate-producing bacterial strains selected from the group consisting of Anaerostipes and Eubacterium. In various embodiments, probiotic bacteria are provided in the disclosed compositions at a concentration of 1 to 1 billion, 1 billion to 5 billion, 5 billion to 10 billion, 10 billion to 20 billion, or greater than 20 billion colony-forming units (CFU) per dose.

[0019] In some embodiments, compositions provided by the present disclosure include one or more prebiotics combined with one or more probiotics in a volume at a multiple > 0 and less than or equal to 1, or > 1 and less than or equal to 2, or > 2 and less than or equal to 3, or > 3 and less than or equal to 4, or greater than 4.

[0020] In some embodiments, compositions provided by the present disclosure are formulated for oral ingestion as a powder, optionally dissolved in a drinkable medium (e.g., water, juice, etc.). The powder can also be mixed in a paste or gel prior to oral delivery, and / or may be mixed in another medium for oral ingestion such as food.

[0021] In some embodiments, the disclosed compositions are formulated in a capsule dosage or a pill dosage form, suitable for oral delivery. In those embodiments comprising a pill dosage form, the pill may or may not be formulated with an enteric coating. In some embodiments, the disclosed compositions are formulated for oral delivery via sublingual administration. In some embodiments, the disclosed compositions are formulated as a chewable (e.g., a chewable tablet, wafer, or the like), and / or may also be formulated as a gel or gelatin gummy.

[0022] In some embodiments, the disclosed compositions are formulated as a rectal suppository and / or an enema.

[0023] In any of the above dosage form formulations, the disclosed compositions may include one or more suitable excipient selected from the group consisting of starch, potato starch, com starch, oat bran, cellulose, guar gum, pectin, or other low FODMAP excipient.

[0024] In a second aspect, the present disclosure provides methods for enhancing gut health and / or treating one or more symptoms of gut dysbiosis. In various embodiments, the disclosed methods comprise administering a composition provided by the present disclosure to a subject in need thereof. In various embodiments, the subject may have symptoms associated with conditions associated with low levels of F. prausnitzii or Roseburia, such as ME / CFS, Crohn’s disease, ulcerative colitis, celiac disease, leaky gut, gut dysbiosis, gastrointestinal upset, Long COVID, fatigue, depression, brain fog, cognitive dysfunction, difficulty in concentration, memory loss, or other symptoms or conditions in any combination thereof. In some embodiments, administration of a disclosed composition increases butyrate production in the gut of the subject. In some embodiments, administration of a disclosed composition improves colonocyte function and restores and maintains gastrointestinal tract integrity. In some embodiments, administration of a disclosed composition can ameliorate one or more symptoms of Long CO VID such as fatigue, gastrointestinal upset, memory loss, difficulty in concentration, and others. In various embodiments, symptoms are treated and / or ameliorated by modulating the gut microbiome.

[0025] In various embodiments, the disclosed compositions can be administered once daily, twice daily, three times daily, four times daily, five times daily, six times daily, every other day, every two days, every three days, every four days, every 5 days, every 6 days, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or at any other time interval. In those embodiments where the compositions are formulated as powders for oral delivery, dosing may be achieved by mixing a set volume, for example one teaspoon, into a suitable liquid prior to ingestion.

[0026] DETAILED DESCRIPTION

[0027] Compositions and methods of making such compositions are provided herein that address the afore-mentioned problems. In particular, compositions comprising one or more prebiotics and one or more probiotics are provided. The disclosed compositions may reduce gut dysbiosis and / or leaky gut, and that may be useful in the treatment and / or management of one or more disorders relating to the gut.

[0028] As used herein, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. For example, a polyphenol refers to one or more polyphenols. As such, the terms “a,” “an,” “one or more,” and “at least one” can be used interchangeably. Similarly, the terms “comprising,” “including,” and “having” can be used interchangeably.

[0029] As used herein, unless otherwise specified, the terms “about,” “approximately,” and the like, when used in relation to numerical limitations or ranges, mean that the recited limitation or range may vary by up to 10%. By way of non-limiting example, “about 750” can mean as little as 675 or as much as 825, or any value therebetween. When used in relation to ratios or relationships between two or more numerical limitations or ranges, the terms “about,” “approximately,” and the like mean that each of the limitations or ranges may vary by up to about 10%; by way of non-limiting example, a statement that two quantities are “approximately equal” can mean that a ratio between the two quantities is as little as 0.9: 1.1 or as much as 1.1:0.9 (or any value therebetween), and a statement that a four-way ratio is “about 5:3: 1:1” can mean that the first number in the ratio can be any value of at least 4.5 and no more than 5.5, the second number in the ratio can be any value of at least 2.7 and no more than 3.3, and so on.

[0030] Certain features of the present disclosure are described in the context of separate embodiments but may also be provided in combination in a single embodiment. Conversely, various features of the present disclosure, which are described in the context of a single embodiment may also be provided separately or in any suitable sub-combination(s). All combinations of the disclosed embodiments are specifically embraced by the present disclosure and are disclosed herein as if each and every combination was individually and explicitly disclosed. In addition, all sub-combinations are also specifically embraced by the present disclosure and are disclosed herein as if each and every such sub-combination was individually and explicitly disclosed.

[0031] The present disclosure is not limited to particular embodiments described herein. Terminology used herein for describing particular embodiments only is not intended to be limiting. Any publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. Further, the publication dates provided may be different from actual publication dates, which may need to be independently confirmed.

[0032] Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the methods and compositions disclosed herein, the preferred methods and materials are now described.

[0033] COMPOSITIONS

[0034] In various aspects, the present disclosure provides synbiotic compositions comprising, consisting of, or consisting essentially of, one or more prebiotics and one or more probiotics. In the disclosed compositions, the one or more prebiotics can be any one or more of those disclosed herein; similarly, the one or more probiotics can be one or more of the probiotics disclosed herein. Depending upon the disclosed combination, a synbiotic composition may display synergistic effects.

[0035] Prebiotics

[0036] A “prebiotic” generally refers to a food ingredient that selectively stimulates the growth and / or activity of beneficial bacteria in the gut. The type of prebiotic is not generally limited and can be selected from Acai berries, Acai berry powder, Acai berry extract, Acacia fiber, Acerola cherry powder, Acerola cherry extract, Agave inulin, Almond butter, Almond powder, Almond extract, Almonds, Amla powder, Amla extract, Apple pectin, Apple powder, Apple extract, Arabinogalactan, Artichoke extract, Artichokes, Ashwagandha powder, Ashwagandha extract, Asparagus, Bacillus coagulans, Bamboo shoots, Banana powder, Banana extract, Bananas, Baobab powder, Baobab extract, Barley, Beans, Beets, Benecaries, Berries, Beta-glucan, Betel nut powder, Betel nut extract, Bilberries, Bilberry powder, Bilberry extract, Black currant powder, Black currant extract, Black currants, Blackberries, Blackberry powder, Blackberry extract, Blueberries, Blueberry powder, Blueberry extract, Brazil nut butter, Brazil nut powder, Brazil nut extract, Broccoli, Broccoli powder, Broccoli extract, Burdock root, Burdock root extract, Butternut powder, Butternut extract, Cacao butter, Cacao powder, Cacao extract, Cacao nibs, Cashew butter, Cashew powder, Cashew extract, Cashews, Celeriac, Celery, Cellulose, Cherries, Cherry extract, Cherry powder, Chia seeds, Chicory root, Chicory root extract, Citrus fruits, Citrus pectin, Citrus extract, Coconut butter, Coconut powder, Coconut extract, Coconut water, Coconuts, Coffee cherry powder, Coffee cherry extract, Cranberries, Cranberry powder, Cranberry extract, Dandelion greens, Dandelion extract, Date powder, Date extract, Dates, Elderberries, Elderberry powder, Elderberry extract, Fennel, Fennel extract, Fenugreek, Fenugreek extract, Flaxseeds, Flaxseed extract, Fructooligosaccharides (FOS), Galactomannans, Galactooligosaccharides (GOS), Garlic, Garlic, Garlic extract, Glucomannan, Goji berries, Goji berry powder, Goji berry extract, Grape powder, Grape extract, Grapes, Grapefruit, Grapefruit pectin, Grapefruit extract, Green peas, Green tea, Green tea powder, Green tea extract, Guar gum, Partially hydrolyzed guar gum, Guava, Guava powder, Guava extract, Hazelnut, Hazelnut butter, Hazelnut powder, Hazelnut extract, Hazelnuts, Honey, Human milk oligosaccharides (HMO), Inulin, Isomaltooligosaccharides (IMO), Jerusalem artichoke, Jerusalem artichoke extract, Kale, Kale powder, Kale extract, Karaya gum, Kefir, Kiwi, Kiwi powder, Kiwi extract, Kombucha, Konjac root, Konjac root extract, Lactulose, Lentils, Leeks, Locust bean gum, Macadamia nut butter, Macadamia nut powder, Macadamia nut extract, Macadamia nuts, Maqui berry powder, Maqui berry extract, Matcha powder, Matcha extract, Milk, Mulberry powder, Mulberry extract, Mushrooms, Oat bran, Oats, Okra, Onion powder, Onion extract, Onions, Orange powder, Orange extract, Oranges, Pecan butter, Pecan powder, Pecan extract, Pecans, Pectin, Papaya powder, Papaya extract, Papayas, Parsley, Pecan nut butter, Pectin, Peas, Pineapple powder, Pineapple extract, Pineapples, Pistachio butter, Pistachio powder, Pistachio extract, Pistachios, Plantain, Pomegranate powder, Pomegranate extract, Pomegranates, Potato starch, Psyllium husk, Pumpkin, Pumpkin powder, Pumpkin extract, Pumpkin seeds, Radish, Raffinose, Rhubarb, Rhubarb extract, Rye, Salsify, Sauerkraut, Shallots, Soybeans, Spinach, Spinach powder, Spinach extract, Stachyose, Starch, Strawberries, Strawberry powder, Strawberry extract, Sunflower seeds, Sweet potatoes, Tamarind gum, Tamarind extract, Turmeric powder, Turmeric extract, Turnips, Verbascose, Walnut butter, Walnut powder, Walnut extract, Walnuts, Wheat bran, Whole wheat bread, Xanthan gum, Xylooligosaccharides (XOS), Yacon syrup, Yeast beta-glucan, Yogurt, or combinations of any of the foregoing.

[0037] In some embodiments, the prebiotic is low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP). In some embodiments, the prebiotic is kiwi powder. In some embodiments, the prebiotic is walnut powder. In some embodiments the prebiotic is a combination of kiwi powder and walnut powder. In some embodiments, the prebiotic is partially hydrolysed guar gum (PHGG).

[0038] The one or more prebiotics provided in the disclosed compositions can often be selected to support the growth of a probiotic microbe that is also present in the composition(s). In doing so, the prebiotic is said to support the probiotic microbe. In some embodiments, the prebiotic is an ingredient suitable to supplement a population of Faecalibacterium prausnitzii (F. prausnitzii). In some embodiments, the prebiotic in the disclosed compositions is kiwi powder and the amount provided in the composition is suitable to supplement the population of F. prausnitzii. In some embodiments, the prebiotic supplements the population of Roseburia hominis.

[0039] In a preferred embodiment, the prebiotic is kiwi powder. Kiwi powder is a powdered form of whole kiwi fruit that is typically made by freeze-drying and milling the fruit to preserve its nutrients and sometimes its flavor. Milling freeze-dried kiwi fruit results in a finely ground powder made from the fruit that often includes the skin and seeds. It is a natural source of vitamins (like C and E), potassium, calcium, iron, fiber, and antioxidants. Suitable kiwi powder can be sourced from numerous vendors, for example AoguBio (Xi’an Shaanxi, China).

[0040] Probiotics

[0041] A “probiotic” generally refers to a live microorganism, or microbe (e.g., a bacteria, yeast, or the like), that provide health benefits to a subject when consumed. The type of probiotic is not generally limited and can be selected from Anaerostipes caccae, Anaerostipes hadrus, Aspergillus niger, Aspergillus oryzae, Bacillus clausii, Bacillus coagulans, Bacillus licheniformis, Bacillus subtilis, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium intestinalis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium scardovii, Blautia hansenii, Blautia luti, Blautia obeum, Blautia producta, Blautia schitovskii, Blautia wexlerae, Butyrivibrio alvinus, Butyrivibrio crossotus, Butyrivibrio fibrisolvens, Butyrivibrio hungatei, Butyrivibrio lipocalidus, Butyrivibrio matronii, Butyrivibrio parvus, Butyrivibrio phytoremedians, Butyrivibrio plebeius, Butyrivibrio proteoclasticus, Butyrivibrio pseudofibrisolvens, Butyrivibrio straminisolvens, Butyrivibrio vermis, Butyrivibrio xylanivorans, Clostridium butyricum, Clostridium perfringens, Coprococcus catus, Coprococcus comes, Enterococcus faecalis, Enterococcus faecium, Escherichia coli (E. coli), Eubacterium biforme, Eubacterium brachy, Eubacterium cellulosolvens, Eubacterium combesii, Eubacterium coprostanoligenes, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium eligens, Eubacterium hallii, Eubacterium hadrum, Eubacterium incestum, Eubacterium limosum, Eubacterium minutum, Eubacterium multiforme, Eubacterium nitritogenes, Eubacterium nodatum, Eubacterium pexum, Eubacterium rectale, Eubacterium ruminantium, Eubacterium saburreum, Eubacterium siraeum, Eubacterium tenue, Eubacterium tortuosum, Eubacterium uniforme, Eubacterium ventriosum, Eubacterium xylanophilum Faecalibacterium prausnitzii, Faecalibacterium pseudoprausnitzii, Lactobacillus acidophilus, Lactobacillus agilis, Lactobacillus alimentarius, Lactobacillus aviarius, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus gallinarum, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus lactis, Lactobacillus mucosae, Lactobacillus panis, Lactobacillus pentosus, Lactobacillus plantarum, Lactobacillus psittaci, Lactobacillus pullorum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus ruminis, Lactobacillus saerimneri, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus sharpeae, Lactobacillus suebicus, Lactococcus cremoris, Lactococcus lactis, Leuconostoc lactis, Leuconostoc mesenteroides, Megasphaera elsdenii, Mitsuokella jalaludinii, Odoribacter splanchnicus, Pediococcus acidilactici, Pediococcus pentosaceus, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Saccharomyces boulardii, Saccharomyces cerevisiae, Streptococcus thermophilus, or combinations of any of the foregoing.

[0042] In some embodiments, the disclosed compositions include low histamine-producing probiotic blends of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, or Lactobacillus rhamnosus individually or in any combination thereof. In some embodiments, the disclosed compositions include In some embodiments, the disclosed compositions include Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus.

[0043] In some embodiments, the disclosed compositions comprise probiotic bacteria selected from Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium longum, or any combination of the foregoing. In some embodiments, the disclosed compositions may further comprise butyrate-producing bacterial strains selected from the group consisting of Anaerostipes and Eubacterium.

[0044] In a preferred embodiment, compositions provided by the present disclosure include a probiotic blend of Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus.

[0045] Probiotics are typically measured in colony-forming units (CFU). A CFU is a measure used to estimate the number of viable probiotic cells in a composition. One CFU is a single cell or a group of cells that can reproduce to form a visible colony on a solid growth medium. As such, counting CFUs is an indirect way to count living microorganisms, as it's based on the assumption that each colony originated from a single, viable probiotic cell. In various embodiments, probiotic bacteria are provided in the disclosed compositions at a concentration of 1 to 1 billion, 1 billion to 5 billion, 5 billion to 10 billion, 10 billion to 20 billion, or greater than 20 billion colony-forming units (CFU) per dose. In some embodiments, the disclosed compositions include 100 billion CFU, 110 billion CFU, 120 billion CFU, 130 billion CFU, 140 billion CFU, 150 billion CFU, 160 billion CFU, 170 billion CFU, 180 billion CFU, 190 billion CFU, 200 billion CFU, or more probiotics. Compositions

[0046] The amount of the one or more prebiotics and the amount of the one or more probiotics in any given composition can vary. Generally speaking, a desirable ratio of the two will result in a composition having sufficient prebiotics that will support the growth and life of the one or more probiotics present in that composition. In some embodiments, the ratio of prebiotics to probiotics in the disclosed compositions can be 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, 10:1, 10.5:1, 1:10.5, 1:10, 1:9.5, 1:9, 1:8.5, 1:8, 1:7.5, 1:7, 1:6.5, 1:6, 1:5.5, 1:5, 1:4.5, 1:4, 1:3.5, 1:3, 1:2.5, 1:2, 1:1.5, or any other suitable ratio.

[0047] If there are more than one probiotic species present in a composition, the ratio between each of the probiotic microbes can also vary. In some embodiments, the ratio of one probiotic species to a second probiotic species in the disclosed compositions can be 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, 10:1, 10.5:1, 1:10.5, 1:10, 1:9.5, 1:9, 1:8.5, 1:8, 1:7.5, 1:7, 1:6.5, 1:6, 1:5.5, 1:5, 1:4.5, 1:4, 1:3.5, 1:3, 1:2.5, 1:2, 1:1.5, or any other suitable ratio.

[0048] In some embodiments, suitable compositions provided by the present disclosure include:

[0049] Component Ratio 1 Ratio 2 Ratio 3 Ratio 4 Ratio 5

[0050] Prebiotic 1 2 3 4.5 6

[0051] B. adolescentis 1 1 1 1 1 (probiotic)

[0052] Low Histamine 1 1 1 1 1 Blend* (probiotic)

[0053]

[0054] In the above Table, the Low Histamine Blend is a mixture of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus, for example B. Longum Bl-05, B. Lactis UABla-12, B. Bifidum Bb-06, L. Gasseri Lg-36, L. Salivarius Ls-33, L. Rhamnosus Lr-32 (240 billion CFU / gram, Foods For Gut, USA). In the above table, each Ratio contains a mixture of probiotics that is 50% Bifidobacterium adolescentis, and 50% of a blend of 6 additional probiotics. In some embodiments, the amount of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus in each Ratio is 20% Bifidobacterium longum, 20% Bifidobacterium bifidum, 2.5% Bifidobacterium lactis, 2.5% Lactobacillus gasseri, 0% Lactobacillus salivarius, and 5% Lactobacillus rhamnosus. In some embodiments, the amount of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus in each Ratio is 20% Bifidobacterium longum, 20% Bifidobacterium bifidum, 2.5% Bifidobacterium lactis, 2.5% Lactobacillus gasseri, 2.5% Lactobacillus salivarius, and 2.5% Lactobacillus rhamnosus. In some embodiments, the amount of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus in each Ratio is 8.33% Bifidobacterium longum, 8.33% Bifidobacterium bifidum, 8.33% Bifidobacterium lactis, 8.33% Lactobacillus gasseri, 8.33% Lactobacillus salivarius, and 8.33% Lactobacillus rhamnosus.

[0055] In some embodiments, the prebiotic provided in the above table is kiwi powder.

[0056] In a first preferred embodiment, a composition provided by the present disclosure includes: a prebiotic kiwi powder component specifically including, without limitation, vitamin C, calcium, potassium, and iron; and a probiotic blend component that is 50% Bifidobacterium adolescentis, 20% Bifidobacterium longum, 20% Bifidobacterium bifidum, 2.5% Bifidobacterium lactis, 2.5% Lactobacillus gasseri, 2.5% Lactobacillus salivarius, and 2.5% Lactobacillus rhamnosus. In this embodiment, the ratio of the prebiotic component to the probiotic component is 1:1.

[0057] In a second preferred embodiment, a composition provided by the present disclosure includes: a prebiotic kiwi powder component specifically including, without limitation, vitamin C, calcium, potassium, and iron; and a probiotic blend component that is 50% Bifidobacterium adolescentis, 20% Bifidobacterium longum, 20% Bifidobacterium bifidum, 2.5% Bifidobacterium lactis, 2.5% Lactobacillus gasseri, 2.5% Lactobacillus salivarius, and 2.5% Lactobacillus rhamnosus. In this embodiment, the ratio of the prebiotic component to the probiotic component is 2: 1.

[0058] In a third preferred embodiment, a composition provided by the present disclosure includes: a prebiotic kiwi powder component specifically including, without limitation, vitamin C, calcium, potassium, and iron; and a probiotic blend component that is 50% Bifidobacterium adolescentis, 20% Bifidobacterium longum, 20% Bifidobacterium bifidum, 2.5% Bifidobacterium lactis, 2.5% Lactobacillus gasseri, 0% Lactobacillus salivarius, and 5% Lactobacillus rhamnosus. In this embodiment, the ratio of the prebiotic component to the probiotic component is 1:1.

[0059] In a fourth preferred embodiment, a composition provided by the present disclosure includes: a prebiotic kiwi powder component specifically including, without limitation, vitamin C, calcium, potassium, and iron; and a probiotic blend component that is 50% Bifidobacterium adolescentis, 20% Bifidobacterium longum, 20% Bifidobacterium bifidum, 2.5% Bifidobacterium lactis, 2.5% Lactobacillus gasseri, 0% Lactobacillus salivarius, and 5% Lactobacillus rhamnosus. In this embodiment, the ratio of the prebiotic component to the probiotic component is 2: 1.

[0060] In a fifth preferred embodiment, a composition provided by the present disclosure includes: a prebiotic kiwi powder component specifically including, without limitation, vitamin C, calcium, potassium, and iron; and a probiotic blend component that is 50% Bifidobacterium adolescentis, 8.33% Bifidobacterium longum, 8.33% Bifidobacterium bifidum, 8.33% Bifidobacterium lactis, 8.33% Lactobacillus gasseri, 8.33% Lactobacillus salivarius, and 8.33% Lactobacillus rhamnosus. In this embodiment, the ratio of the prebiotic component to the probiotic component is 1:1.

[0061] In a sixth preferred embodiment, a composition provided by the present disclosure includes: a prebiotic kiwi powder component specifically including, without limitation, vitamin C, calcium, potassium, and iron; and a probiotic blend component that is 50% Bifidobacterium adolescentis, 8.33% Bifidobacterium longum, 8.33% Bifidobacterium bifidum, 8.33% Bifidobacterium lactis, 8.33% Lactobacillus gasseri, 8.33% Lactobacillus salivarius, and 8.33% Lactobacillus rhamnosus. In this embodiment, the ratio of the prebiotic component to the probiotic component is 2:1.

[0062] DOSAGE FORMS

[0063] In certain aspects, compositions of the disclosure may comprise additional agents to provide a form suitable for administration to an individual subject. Such agents may be described as biologically inactive and can be administered to subjects without causing deleterious interactions with the active agents. Examples of suitable agents include, but are not limited to, excipients such as starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol, and the like. Additional examples of suitable agents include, but are not limited to, vitamins, minerals, trace elements, oils (e.g., olive oil) antioxidants, pharmaceutical agents ( / .< ., drugs), fiber, buffering agents, antacids, stabilizers, sweetening agents, flavoring agents, dyes, or coloring agents. Examples of such additional agents are disclosed in US Patent Publication No. 2013 / 0095204, US Patent Publication No. 2007 / 0077279 and US Patent No. 9,839,624.

[0064] Compositions of the disclosure can take the form of solutions, suspensions, emulsions, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. In one embodiment, the disclosed compositions are provided in one or more capsule dosage forms (see, e.g., Grosswald et al., U.S. Pat. No. 5,698,155). Preferred compositions provided by the present disclosure are formulated for oral delivery.

[0065] Compositions for oral delivery may be in the form of tablets, lozenges, aqueous or oily suspensions, granules, powders, emulsions, capsules, syrups, or elixirs, for example. Orally administered compositions may contain one or more optional agents, for example, sweetening agents such as fructose, aspartame or saccharin, flavoring agents such as peppermint, oil of wintergreen, or cherry coloring agents and preserving agents, to provide a pharmaceutically palatable preparation. Moreover, where in tablet or pill form, the compositions may be coated to delay disintegration and absorption in the gastrointestinal tract, thereby providing a sustained action over an extended period of time. Selectively permeable membranes surrounding an osmotically active driving compound are also suitable for orally administered compounds and compositions of the present disclosure. In these later platforms, fluid from the environment surrounding the capsule is imbibed by the driving compound, which swells to displace the agent or agent composition through an aperture. These delivery platforms can provide an essentially zero order delivery profile as opposed to the spiked profiles of immediate release formulations. A time delay material such as glycerol monostearate or glycerol stearate may also be used. Oral compositions can include standard vehicles such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Such vehicles are preferably of pharmaceutical grade.

[0066] For oral liquid preparations such as, for example, suspensions, elixirs and solutions, suitable carriers, excipients or diluents include water, saline, alkyleneglycols (e.g., propylene glycol), polyalkylene glycols (e.g., polyethylene glycol) oils, alcohols, slightly acidic buffers between pH 4 and pH 6 (e.g, acetate, citrate, ascorbate at between about 5 mM to about 50 mM), etc. Additionally, flavoring agents, preservatives, coloring agents, bile salts, acylcamitines and the like may be added.

[0067] Compositions may also take a form for administration via other routes. For buccal administration, the compositions may take the form of tablets, lozenges, etc. formulated in conventional manner. Liquid formulations suitable for use with nebulizers and liquid spray devices and EHD aerosol devices will typically include a composition provided by the present disclosure with a pharmaceutically acceptable vehicle. Preferably, the pharmaceutically acceptable vehicle is a liquid such as alcohol, water, polyethylene glycol or a perfluorocarbon. Optionally, another material may be added to alter the aerosol properties of the solution or suspension of compositions of the present disclosure. Preferably, this material is liquid such as an alcohol, glycol, polyglycol or a fatty acid. Other methods of formulating liquid solutions or suspension suitable for use in aerosol devices are known to those of skill in the art (see, e.g, Biesalski, U.S. Pat. No. 5,112,598; Biesalski, U.S. Pat. No. 5,556,611). A composition provided by the present disclosure may also be formulated in rectal or vaginal compositions such as suppositories or retention enemas, e.g, containing conventional suppository bases such as cocoa butter or other glycerides. In addition to the formulations described previously, a composition provided by the present disclosure may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, a composition provided by the present disclosure may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

[0068] METHODS OF MAKING COMPOSITIONS

[0069] As noted herein, the present disclosure provides synbiotic compositions comprising one or more prebiotics and one or more probiotics. In some embodiments, the synbiotic compositions comprise a prebiotic component and a probiotic component in a specific ratio. Generally, each of the prebiotic components and the probiotic components are sources in dry powder form. For example, in those embodiments where the prebiotic is kiwi powder, the component itself is prepared by milling freeze dries kiwi fruit into a powder. Similarly, most probiotics come in a dry powdered (e.g., lyophilized) form, as can many excipients and additive, as disclosed herein.

[0070] In various aspects, then, compositions provided by the present disclosure are made via the blending of dry, sometimes powdered, components together. To ensure that all components are uniformly mixed together, the dry powdered ingredients are typically blended carefully to produce a uniform mixture. This blending process ensures that each dosage form (dry powder formulation, tablet, capsule, sachet, or other dosage form) delivers a consistent amount of a composition from dose to dose. Each component of the formulation is first weighed and dispensed according to the desired, final formulation parameters. Materials can be sieved or milled to break up clumps and achieve a visually consistent particle size.

[0071] The weighed and prepared powders are then transferred to a blender. The type of blender used is not at all limiting and indeed any can be utilized as long as it is capable of generating a homogenous, or nearly homogenous, mixture of dry components. Several types of blenders are commonly used for this purpose, including V-blenders, double-cone blenders, bin blenders, and high-shear mixers. The choice of equipment depends on the properties of the powders and the desired intensity of mixing. Free-flowing powders are often processed in a V-blender or double-cone blender, which use a gentle tumbling motion, while more cohesive or poorly flowing materials may require a high-shear mixer to achieve a uniform blend.

[0072] Materials are typically loaded into the blender in a defined sequence, often beginning with diluents or fillers, followed by the prebiotics and probiotics. In those embodiments where the ratio of one component to another is not uniform, often the higher concentration component will be loaded into the blender before the lower concentration component. The blend is mixed for a validated period of time and at a controlled rotation speed to achieve uniformity without over-mixing. Toward the end of the blending cycle, lubricants such as magnesium stearate may be added and mixed briefly to ensure even distribution without adversely affecting, for example, capsule loading capabilities, tablet compressibility, and / or dissolution characteristics.

[0073] After blending, samples are collected from various points in the blender to test for content uniformity. This testing confirms that all of the components are evenly distributed throughout the batch. If results meet specification, the blend is discharged into lined containers to protect against contamination and segregation. The blended powder is then transferred to the next stage of manufacturing, such as granulation, compression, or encapsulation, depending on the type of dosage form being produced.

[0074] Throughout this process, strict Good Manufacturing Practice (GMP) standards are followed to the extent possible. Environmental conditions such as humidity and temperature are controlled to minimize clumping or electrostatic buildup, which can affect mixing performance. Each step — from weighing and blending to sampling and documentation — is performed and recorded in accordance with the facility’s validated procedures to ensure consistent product quality and regulatory compliance.

[0075] METHODS, DOSING

[0076] Compositions provided by the present disclosure may generally be used to prevent or treat various conditions and / or to generally improve the health of a subject. As used herein, “subject” refers to any human or non-human animal. Examples include, but are not limited to, humans, non-human primates, such as chimpanzees, apes and other monkey species; domestic mammals (e.g., dogs and cats); laboratory animals (e.g., mice, rats guinea pigs); birds, and bats. Subjects of any age or race are covered by the present disclosure.

[0077] Compositions provided by the present disclosure are useful for the treatment of any condition or disease associated with gut dysbiosis. For example, compositions provided by the present disclosure are useful to enhance gut health and / or treat one or more symptoms of gut dysbiosis. In various embodiments, methods of treating a disease and or ameliorating one or more symptoms of a disease associated with gut dysbiosis are provided, the methods comprising administering a composition provided by the present disclosure to a subject in need thereof. In various embodiments, the subject may have symptoms associated with conditions associated with low levels of F. prausnitzii or Roseburia, such as ME / CFS, Crohn’s disease, ulcerative colitis, celiac disease, leaky gut, gut dysbiosis, gastrointestinal upset, Long COVID, fatigue, depression, brain fog, cognitive dysfunction, difficulty in concentration, memory loss, or other symptoms or conditions in any combination thereof. In some embodiments, the present disclosure provides methods of treating Long COVID, inclusive of any fatigue, depression, brain fog, cognitive dysfunction, difficulty in concentration, memory loss, or other symptoms or conditions in any combination thereof that accompany Long CO VID.

[0078] The amount (weight amount, concentration, etc.) of a composition suitable for use in a method of treatment can be determined by the amount of a composition desirable to deliver to a subject, the severity of the symptoms experienced by the subject, and / or the judgment of an attending health care professional. The desired amount may depend on the nature of the conditions or disease to be treated, and can be determined by standard clinical techniques known in the art. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dose ranges. In some embodiments, the amount of a composition administered will be dependent on, among other factors, the subj ect being treated, the weight of the subject, the severity of the disease, the manner of administration and the judgment of any prescribing health care provider.

[0079] In some embodiments, an amount of a composition is administered to a subject to deliver an amount of polyphenol in the range of from about 1 microgram (pg) to about 2,000 milligrams (mg). In some embodiments, the amount of a single dose of a composition administered to a subject is at least 5 pg, at least 10 pg, at least 25 pg, at least 50 pg, at least 100 pg, at least 500 pg, at least 1 mg, at least 5 mg, at least 10 mg, at least 25 mg, at least 50 mg, at least 100 mg, at least 250 mg, at least 50 mg, at least 1000 mg, or at least 2000 mg.

[0080] In some embodiments, a dose of a composition may be delivered by a single administration or by multiple administrations. In some embodiments, a dose of a composition may delivered orally. In some embodiments, a dose of a composition may be administered once per day, twice per day, three times per day, four times per day, once every two days, once every three days, once per week, once every two weeks, once per month, or on any schedule necessary to achieve the desired effect.

[0081] In some embodiments, a method of treating a disease and or ameliorating one or more symptoms of a disease associated with gut dysbiosis in a subject comprises administering to the subject a dose of a composition provided by the disclosure once per day. The dose of the composition can, in some embodiments, start at a low dose that can be increased to account for the subj ect’ s tolerance to the composition and the desired outcome and / or effect. In various embodiments, a dose of a composition provided by the present disclosure can be 1 g / day, 1.1 g / day, 1.2 g / day, 1.3 g / day, 1.4 g / day, 1.425 g / day, 1.5 g / day, 1.6 g / day, 1.7 g / day, 1.8 g / day, 1.9 g / day, 2 g / day, 2.1 g / day, 2.2 g / day, 2.3 g / day, 2.4 g / day, 2.5 g / day, 2.6 g / day, 2.7 g / day, 2.8 g / day, 2.85 g / day, 2.9 g / day, 3 g / day, 3.1 g / day, 3.2 g / day, 3.3 g / day, 3.4 g / day, 3.5 g / day, 3.6 g / day, 3.65 g / day, 3.7 g / day, 3.8 g / day, 3.9 g / day, 4 g / day, 4.1 g / day, 4.2 g / day, 4.3 g / day, 4.4 g / day, 4.5 g / day, 4.6 g / day, 4.7 g / day, 4.8 g / day, 4.9 g / day, 5 g / day, 5.1 g / day, 5.2 g / day, 5.3 g / day, 5.4 g / day, 5.5 g / day, 5.6 g / day, 5.7 g / day, 5.8 g / day, 5.9 g / day, 6 g / day, 6.1 g / day, 6.2 g / day, 6.3 g / day, 6.4 g / day, 6.5 g / day, 6.6 g / day, 6.7 g / day, 6.8 g / day, 6.9 g / day, 7 g / day, 7.1 g / day, 7.2 g / day, 7.3 g / day, 7.4 g / day, 7.5 g / day, 7.6 g / day, 7.7 g / day, 7.8 g / day, 7.9 g / day, 8 g / day, 8.1 g / day, 8.2 g / day, 8.3 g / day, 8.4 g / day, 8.5 g / day, 8.6 g / day, 8.7 g / day, 8.8 g / day, 8.9 g / day, 9 g / day 9.1 g / day, 9.2 g / day, 9.3 g / day, 9.4 g / day, 9.5 g / day, 9.6 g / day, 9.7 g / day, 9.8 g / day, 9.9 g / day, 10 g / day, or more. An example of a suitable dosing regimen is as follows: the dose of a disclosed composition administered may be initially 1 g / day, 1.1 g / day, 1.2 g / day, 1.3 g / day, 1.4 g / day, 1.5 g / day, 1.6 g / day, 1.7 g / day, 1.8 g / day, 1.9 g / day, or 2 g / day. In some embodiments, the initial dose may be about 1.4 g / day, or 1.425 g / day. Such initial dosing may continue for a period of days or weeks, depending on the desired outcome. After the initial dosing regimen is complete, the dose administered may increase to 2.1 g / day, 2.2 g / day, 2.3 g / day, 2.4 g / day, 2.5 g / day, 2.6 g / day, 2.7 g / day, 2.8 g / day, 2.9 g / day, or 3 g / day. In some embodiments, this increased dose may be about 2.8 g / day or 2.85 g / day. Such increased dosing may continue for a period of days or weeks, depending on the desired outcome. After this increased dosing regimen is complete, the dose administered may increase again to a daily maintenance dose of 3.1 g / day, 3.2 g / day, 3.3 g / day, 3.4 g / day, 3.5 g / day, 3.6 g / day, 3.7 g / day, 3.8 g / day, 3.9 g / day, or 4 g / day. In some embodiments, this maintenance dose may be about 3.7 g / day or 3.65 g / day. Maintenance dosing may continue indefinitely.

[0082] In some embodiments, the composition may be administered in conjunction with one or more other treatments for the condition or disease.

[0083] DISCUSSION

[0084] Microbial dysbiosis of the gut is implicated in many conditions including Long COVID, Irritable Bowel Syndrome (IBS), Crohn’s Disease, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS), Multiple Sclerosis (MS), Ulcerative Colitis (UC), Celiac disease, Chronic inflammation, Intestinal fistula, Leaky gut syndrome, Sepsis, Autonomic disorders, Dysautonomia, Mitochondrial dysfunction, Immune system health including the regulation, and function of T-cell exhaustion, Treg cells, helper cells, Immunomodulatory and auto-immune disorders such as lupus, Conditions known and unknown related to the brain-gut axis, States of mental health and conditions, such as depression, anxiety, suicidal ideation, social function, etc., Autism, Obesity, Diabetes, Digestion, Liver function, cardiopulmonary function, Clotting, Endocrine dysfunction, Cancer, Cancer prevention, Metabolic syndromes, Neurodegenerative conditions, Parkinson’s disease (PD), Alzheimer’s disease (AD), Lewy body dementia, Huntington’s Disease, amyotrophic lateral sclerosis (ALS), Malnutrition, nutrient absorption, Sleep patterns, Viral persistence, Appetite regulation and eating, Menstrual regularity, Gas and bloating, Aberrant fatty acid metabolism, Fatty liver disease, Plaque, dental disease, Gingivitis, Halitosis, Ulcers, Bacterial infections, overgrowth, imbalance, C. difficile, H. pylori, Bacterial gastroenteritis, Staphylococcus aureus, Bacillus Cereus, Campylobacter, Yersinia, Vibrio, Bowel infections, Small intestinal bacterial overgrowth (SIBO), Fungal infections, overgrowth, imbalance, Viral infections, Viral persistence, Virus reactivation, Helminths and worms, Parasites, Food poisoning, Atopic dermatitis (AD), or eczema, Memory loss (Short term, Long term), Constipation, Diarrhea, Obesity, Long COVID, post-exertional malaise (PEMS), postural orthostatic tachyardia syndrome (POTS), brain fog, and more. The foregoing may not be a comprehensive list of known conditions related to dysbiosis of the microbiome. Gastrointestinal diseases: Gastroenteritis, Antibiotic associated diarrhea, Traveler’s diarrhea, C. Difficile infection, Inflammatory bowel disease, Celiac disease, H. Pylori infection, Treatment of Lactose Intolerance. Allergy. Respiratory diseases: Asthma, Cystic Fibrosis, Respiratory infections and COVID-19. Neurological and Psychiatric diseases. Liver diseases and Hepatic Encephalopathy. Urinary tract infections. Metabolic syndrome and Cardiovascular diseases: Diabetes, Obesity, Cardiovascular disease, High Cholesterol, lipid disease. Cancer. Oral Diseases: Gingivitis, Periodontitis, Dental caries, Halitosis, Oral candidiasis. Autoimmune Diseases: Sjogren’s syndrome, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Multiple Sclerosis. Bacterial Vaginosis. Osteoporosis.

[0085] In addition, research continues and there are constant discoveries of additional conditions that are related to dysbiosis of the microbiome and other conditions of the gut.

[0086] There is an axis between the microbiota in the gut and the brain. The interaction between the gut microbiota and central nervous system (CNS) regulates neuropsychiatric symptoms, diverse neurodegenerative diseases, developmental disorders, autonomic nervous system, cognitive function and mood. Gut bacteria produce metabolites, such as SCFAs (acetate, propionate, and butyrate), tryptophan metabolites (indole and its derivatives), and microbial neurotransmitters (GABA, serotonin, and catecholamines), which become activation signals at the enteric nervous system (ENS) level in order to facilitate communication between the gut and brain via immune cells and cytokines. Depending on the composition of the gut microbiota, this may lead to protective effects when in balance or favor disease development in dysbiosis: CNS, central nervous system; SCFAs, short-chain fatty acids; GABA, y-aminobutyric acid; ENS, enteric nervous system; Treg, regulatory T lymphocyte.

[0087] There is an axis between the microbiota in the gut and the skin. Microbiota-gut-skin axis. Bidirectional communication between the gut microbiota and skin occurs through bacterial metabolites, bacterial translocation, and immune system modulation, either by pathogens or probiotics, (a) Intestinal dysbiosis plays an important role in the inflammatory state of the skin in several dermatoses through the increase in proinflammatory metabolites, cytokines, and lymphocytes, (b) Probiotics help restore the balance through the increase in antiinflammatory metabolites, such as SCFAs, immune cells, such as Treg lymphocytes, and cytokines, such as IL- 10, to reduce and control the inflammation produced during these cutaneous pathologies: SCFAs, short-chain fatty acids; APC, antigen-presenting cell. There is an axis between the microbiota in the gut and the lung or respiratory system. The microbiota-gut-lung communication is bidirectional, through the lymph and blood circulation, being conducted by metabolites released in both mucous membrane tissues. The presence of intestinal dysbiosis during lung disease plays a key role through its immunomodulatory capacity. In COPD, ventilation-perfusion mismatch leads to intestinal tissue hypoxia and epithelial cell damage associated with dysbiosis, which induces a decrease in SCFA secretion, an increase in the Thl7 / Treg ratio, and the secretion of proinflammatory cytokines, which correlates with pulmonary inflammation. In asthma, intestinal dysbiosis correlates positively with disease severity. The decrease in A. muciniphila and increase in the alveolar epithelium permeability are associated with a decrease in Bacteroides acidifaciens and butyric acid concentration. In COVID-19, SARS-CoV-2 decreases the ACE2 expression in the gut, which is associated with gut dysbiosis, with an increase in pathogens and a decrease in probiotic bacteria. This leads to an increase in intestinal permeability, proinflammatory markers, neutrophil recruitment, and cell activation in the pulmonary tissue. Prebiotic, probiotic, and postbiotic supplementation restores the gut microbiota (GM), reduces inflammation in the airways, restores the balance between cytokine and chemokine production, decreases leucocyte recruitment, and increases the SCFA concentration: COPD, chronic obstructive pulmonary disease; SCFAs, short-chain fatty acids; COVID-19, coronavirus disease 2019; FEV1, forced expiratory volume in the first second; ALT, alanine transaminase; AST, aspartate transaminase; LDH, lactate dehydrogenase; CK, creatine kinase; Treg, regulatory T lymphocyte.

[0088] There is an axis between the microbiota in the gut and the heart or cardiovascular system. Through the gut microbiota and heart communication axis, intestinal dysbiosis (ID) may trigger or exacerbate heart diseases, such as hypertension, atherosclerosis, CAD, and even heart failure. In this case, ID favors the presence of bacteria that produce toxic metabolites, such as TMA, TMAO, indoxyl sulfate, and other endotoxins, which are responsible for the detrimental relationship between gut and heart. On the other hand, a balanced gut microbiota favors the production of SCFAs, bile acids, and other compounds that promote homeostatic processes in the heart: CAD, coronary artery disease; TMA, trimethylamine; TMAO, trimethylamine N-oxide; SCFAs, short-chain fatty acids.

[0089] There is an axis between the gut microbiota and metabolism. In obesity and Type 2 Diabetes Mellitus (T2DM), the inflammatory state is not produced by infections or autoimmune factors but by metabolic dysfunction in a condition known as metainflammation. The most abundant bacterial phyla of the gut microbiota are Firmicutes and Bacteroidetes; however, people with T2DM or obesity have an imbalanced proportion of these bacteria in contrast to healthy subjects. In addition, there is an increase in bacterial translocation and blood LPS, which promotes proinflammatory cytokines such as IL-6 and TNF-a. Prebiotic and probiotic intake promotes the positive modulation of the gut microbiota, produces greater saccharolytic and SCFAs fermentation, improves epithelial barrier function, and increases the abundance of anti-inflammatory markers such as IL-4 and IL- 10. The increase in SCFAs impacts the release of intestinal hormones PYY and GLP-1 and is associated with the inhibition of triglyceride and cholesterol synthesis. It also reduces bacterial translocation and the production of proinflammatory markers: T2DM, type 2 diabetes mellitus; SCFAs, short-chain fatty acids; PYY, peptide YY; GLP-1, glucagon-like peptide 1; CRP, C-reactive protein. Other axes may include and are not limited to the circulatory system, the lymphatic system, the immune system, the muscle system, the nervous system.

[0090] Butyrate is made in the gastrointestinal tract predominantly by a number of microorganisms. Current research suggests that butyrate serves as the main energy source for the cells lining the gut, fulfilling up to 70% of their energy needs, supporting the gut's immune system, and can protect against digestive tract diseases. Colonocytes (the cells that line the colon) use butyrate as their main source of energy.

[0091] Probiotic bacteria may include but are not limited to Anaerostipes caccae, Anaerostipes hadrus, Aspergillus niger, Aspergillus oryzae, Bacillus clausii, Bacillus coagulans, Bacillus licheniformis, Bacillus subtilis, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium intestinalis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium scardovii, Blautia hansenii, Blautia luti, Blautia obeum, Blautia producta, Blautia schitovskii, Blautia wexlerae, Butyrivibrio alvinus, Butyrivibrio crossotus, Butyrivibrio fibrisolvens, Butyrivibrio hungatei, Butyrivibrio lipocalidus, Butyrivibrio matronii, Butyrivibrio parvus, Butyrivibrio phytoremedians, Butyrivibrio plebeius, Butyrivibrio proteoclasticus, Butyrivibrio pseudofibrisolvens, Butyrivibrio straminisolvens, Butyrivibrio vermis, Butyrivibrio xylanivorans, Clostridium butyricum, Clostridium perfringens, Coprococcus catus, Coprococcus comes, Enterococcus faecalis, Enterococcus faecium, Escherichia coli (E. coli), Eubacterium biforme, Eubacterium brachy, Eubacterium cellulosolvens, Eubacterium combesii, Eubacterium coprostanoligenes, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium eligens, Eubacterium hallii, Eubacterium hadrum, Eubacterium incestum, Eubacterium limosum, Eubacterium minutum, Eubacterium multiforme, Eubacterium nitritogenes, Eubacterium nodatum, Eubacterium pexum, Eubacterium rectale, Eubacterium ruminantium, Eubacterium saburreum, Eubacterium siraeum, Eubacterium tenue, Eubacterium tortuosum, Eubacterium uniforme, Eubacterium ventriosum, Eubacterium xylanophilum, Faecalibacterium prausnitzii, Faecalibacterium pseudoprausnitzii, Lactobacillus acidophilus, Lactobacillus agilis, Lactobacillus alimentarius, Lactobacillus aviarius, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus gallinarum, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus lactis, Lactobacillus mucosae, Lactobacillus panis, Lactobacillus pentosus, Lactobacillus plantarum, Lactobacillus psittaci, Lactobacillus pullorum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus ruminis, Lactobacillus saerimneri, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus sharpeae, Lactobacillus suebicus, Lactococcus cremoris, Lactococcus lactis, Leuconostoc lactis, Leuconostoc mesenteroides, Megasphaera elsdenii,inii, Odoribacter splanchnicus, Pediococcus acidilactici, Pediococcus pentosaceus, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Saccharomyces boulardii, Saccharomyces cerevisiae, Streptococcus thermophilus, and other probiotic bacteria.

[0092] Bacteria that make butyrate in the GI tract may include but are not limited to Butyrivibrio alvinus, Butyrivibrio crossotus, Butyrivibrio fibrisolvens, Butyrivibrio hungatei, Butyrivibrio lipocalidus, Butyrivibrio matronii, Butyrivibrio parvus, Butyrivibrio phytoremedians, Butyrivibrio plebeius, Butyrivibrio proteoclasticus, Butyrivibrio pseudofibrisolvens, Butyrivibrio straminisolvens, Butyrivibrio vermis, Butyrivibrio xylanivorans, faecalibacterium prausnitzii (f. prausnitzii), Roseburia intestinalis, Roseburia Hominis, Eubacterium rectale, Roseburia spp., Clostridium butyricum, Clostridium beijerinckii, and Eubacterium Hallii, etc.

[0093] Addressing chronic inflammation may be useful in addressing many conditions. While there are many approaches to reducing inflammation, such as administering steroids, natural approaches through the gut microbiome may have fewer side effects and may confer additional benefits. F. Prausnitzii is an example of an organism that is generally considered to be anti-inflammatory when growing in the gut microbiome.

[0094] Research has shown that f. prausnitzii is often abnormally low in the gut microbiome of people with ME / CFS, Crohn’s disease, Ulcerative colitis, Celiac disease and Long COVID. In Long COVID, two of the main butyrate producers, f. prausnitzii and Roseburia hominis may be abnormally low, resulting in inadequate levels of butyrate production Inadequate levels of butyrate may cause the colon cells to become leaky and allow toxins, bacteria, fungi, viruses, parasites and other harmful substances to pass into the bloodstream. When bacteria and toxins leak through the colon cell tight junctions, this can increase inflammation in the body and may increase autoimmunity via molecular mimicry.

[0095] Current research suggests that irritable bowel syndrome may be helped if the leaky gut is mitigated.

[0096] F. prausnitzii can play an important role in gut health, metabolic processes, mitochondrial function, immune function, cancer prevention and mitigation, disease prevention and mitigation through its secreted metabolite — butyrate. Butyrate facilitates the regeneration of colonocytes, thus maintaining intestinal integrity. Moreover, butyrate also induces regulatory T cell (Treg) development to promote intestinal mucosal immune tolerance and maintain the balance between Thl7 and Treg cells to prevent intestinal inflammation. This evidence highlights the importance of the gut microbiota in intestinal disease.

[0097] Prebiotics are nutrients, polyphenols, compounds, or other substances that pass through the stomach and into the intestines to promote the growth of bacteria in the intestines. Microorganisms take up prebiotics and use them to sustain colonies, support internal and external metabolic processes, produce metabolites such as but not limited to butyrate. Mechanisms of actions include and are not limited to regulatory T cell development, regulation of the immune system and immune response, modulation of inflammation and inflammatory pathways, butyrate production, hormone regulation, metabolic regulation, organ and system support, tissue support, regulation of intracellular gaps, regulation of nerve impulses, myelination, ion transfer, modulation of bacterial growth, modulation of fungal growth, modulation of microbial growth, cytokine production, cortisol production, stress, cell senescence, cerebrospinal fluid clearance, neuronal generation, astrocyte regulation, glial cell regulation, insulin regulation, adrenergic and adrenaline regulation, testosterone regulation, estrogen regulation, endothelial cell health, endothelial support, blood cell support, blood cell production, musculoskeletal function, lactate clearance, blood pressure regulation, heart rate regulation, pulmonary regulation, regulation of fibrosis formation, where regulation is the maintenance, inhibition or enhancement of the component being regulated.

[0098] High FODMAP compounds: Some compounds are high in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP). Such high FODMAP compounds are actively metabolized by gastrointestinal microbes and support healthy population ratios. High FODMAP compounds, however, may be poorly absorbed by the small intestine in some people, and have been shown to exacerbate and contribute to symptoms of gastrointestinal inflammation in conditions e.g. irritable bowel disease / syndrome, Celiac disease, Crohn’s disease, leaky gut syndrome.

[0099] Low FODMAP diets are often employed to reduce GI distress and inflammation. Low FODMAP prebiotic compounds can be used to sustain and support healthy populations of the GI microbiome. Low FODMAP compounds can promote the growth of particular organisms such as f. prausnitzii and the Roseburia species.

[0100] Low FODMAP foods and ingredients include Vegetables and Legumes: Alfalfa, Bamboo shoots, Bean sprouts, Beetroot, Black beans, Bok choy / pak choi, Broccoli, Broccolini, Brussels sprouts, Butternut squash, Cabbage, Callaloo, Carrots, Celeriac, Celery, Chicory leaves, Chickpeas, Chilli, Chives, Cho cho, Choy sum, Collard greens, Corn / sweet corn, Courgette, Cucumber, Eggplant / aubergine, Fennel, Fermented cabbage e.g. sauerkraut, Green beans, Green pepper / green bell pepper / green capsicum, Ginger, Kale, Karela, Leek leaves, Lentils - in small amounts, Lettuce: Butter lettuce, Iceberg lettuce, Radicchio lettuce, Red coral lettuce, Rocket lettuce, Romaine / Cos lettuce;, Marrow, Okra, Olives, Parsni, Peas, snow peas, Pickled gherkins, Pickled onions, large, Potat, Pumpkin, Pumpkin, canned, Radis, Red peppers / red bell pepper / red capsicu, Scallions / spring onions (green part), Seaweed / nori, Silverbeet / char, Spaghetti squash, Spinach, Baby Spinach, Squash, Sun-dried tomatoes, Swede, Swiss chard, Sweet potato, Tomato, Tomato juice, Tomatillo, Turnip, Water chestnuts, Water Spinach, Yam, Zucchini. Fruit: Ackee, Applesauce, Bananas, Bilberries, Blueberries, Breadfruit, Carambola, Cantaloupe, Cranberry, Clementine, Coconut, Cranberry juice, Dates, Dragon fruit, Lingonberries, Grapes, Guava, Honeydew and Galia melons, Jackfruit, Kiwifruit, Lemon including lemon juice, Lime including lime juice, Mandarin, Orange, Passion fruit, Paw paw, Papaya, Pineapple, Plantain, peeled, Prickly pear / nopales, Raspberry, Rhubarb, Strawberry, Tamarind, Tangelo. Meats, Poultry and Meat Substitutes: Beef, Chicken, Chorizo, Foie gras, Kangaroo, Lamb, Pork, Prosciutto, Quom, mince, Turkey. Fish and Seafood: Canned tuna; Fresh fish e.g.: Cod, Haddock, Plaice, Salmon, Trout, Tuna, Crab, Lobster, Mussels, Oysters, Prawns, Shrimp. Cereals, Grains, Breads, Biscuits, Pasta, Nuts and Cakes: Wheat free breads, Gluten free breads, Breads as Com bread, Rice bread, Spelt sourdough bread, Potato flour bread, Wheat free or gluten free pasta, Bread, including small doses of whole wheat bread, Almonds, Brazil nuts, Bulgur , Buckwheat, Buckwheat flour, Buckwheat noodles, Brown rice / whole grain rice, Chestnuts, Chips, plain / potato crisps, plain, Cornflour / maize, Crispbread, Corncakes, Cornflakes, Corn, creamed and canned, Com tortillas, Crackers, plain, Flax seeds / linseeds, Flaxseed Oil, Hazelnuts, Kellogg's Com Flakes, Crispix, Frosted Flakes, Frosted Krispies, Rice Krispies, Macadamia nuts, Millet, Mixed nuts, Oatmeal, Oats, Oatcakes, Pastry, filo / phyllo, Pastry, puff, Peanuts, Pecans, Pine nuts, Polenta, Popcorn, Porridge and oat based cereals, Potato flour, Pretzels, Quinoa, Pasta, wheat, Rices as, Basmati rice, Bomba rice, Brown rice, Rice noodles, White rice, Wild rice, Rice bran, Rice cakes, Rice crackers, Rice flakes, Rice flour, Seeds asChia seeds, Dill seeds, Egusi seeds, Hemp seeds, Poppy seeds, Pumpkin seeds, Sesame seeds, Sunflower seeds, Starch, maize, potato and tapioca, Sorghum, Tortilla chips / com chips, Walnuts. Condiments, Dips, Sweets, Sweeteners and Spreads: Aspartame, Acesulfame K, Almond butter, Barbecue sauce, Capers in vinegar, Capers, Chocolate as Dark chocolate, Milk chocolate, White chocolate, Chutney, Dijon mustard, Erythritol (E968 / 968), Fish sauce, Golden syrup, Glucose, Glycerol (E422 / 422), Jam / jelly, strawberry, Jam / jelly, raspberry, Ketchup, Maple syrup, Marmalade, Marmite, Mayonnaise - ensuring no garlic or onion in ingredients, Miso paste, Mustard, Oyster sauce, Pesto sauce, Peanut butter, Rice malt syrup, Saccharine, Shrimp paste, Soy sauce, Sriracha hot chilli sauce, Stevia, Sweet and sour sauce, Sucralose, Sugar - also called sucrose, Tahini paste, Tamari sauce, Tamarind paste, Tomato sauce (outside USA), Vegemite, Vinegars as Apple cider vinegar, Balsamic vinegar, Rice wine vinegar, Worcestershire sauce. Drinks and Protein Powders: Alcohol -is an irritant to the gut, limited intake advised: Clear spirits such as Vodka, Gin, Wine -limited to one drink, Coffee as, Espresso coffee, regular or decaffeinated, black, Espresso coffee, regular or decaffeinated,, Instant coffee, regular or decaffeinated, black, Instant coffee, regular or decaffeinated, with milk (dairy, lactose-free, whole, lowfat, nonfat, skim, half and half, oat, coconut, soy, almond), Coconut milk, Coconut water, Drinking chocolate powder, Fruit juice, Kvass, Lemonade, Protein powders:, Egg protein, Rice protein, Sacha Inchi protein, Whey protein isolate, Soya milk made with soy protein, Sugar free fizzy drinks / soft drinks / soda - such as diet coke, in low quantities as , aspartame and acesulfame k can be irritants, 'Sugar' fizzy drinks / soft drinks / soda that do not contain HFCS such as lemonade, cola. , Limit intake due to these drinks being generally unhealthy and can cause gut irritation. Tea: Black tea, weak e.g. PG Tips, Chai tea, weak, Fruit and herbal tea, weak - ensure no apple added, Green tea, Peppermint tea, White tea, Water. Dairy Foods and Eggs: Butter, Cheese as, American Cheese, Brie, Camembert, Cheddar, Cottage, Cream Cheese, Feta, Goat / chevre, Haloumi, Monterey Jack, Mozzarella, Paneer, Parmesan, Ricotta, Swiss, Dairy free pudding, Eggs, Margarine, Milk as Almond milk, Hemp milk, Lactose free milk, Macadamia milk, Oat milk, Rice milk, Sorbet, Soy protein, Swiss cheese, Tempeh, Tofu - drained and firm varieties, Whipped cream, Yoghurt as Coconut yoghurt, Greek yoghurt, Lactose free yoghurt, Goats yoghurt, Soy yoghurt Herbs: Basil, Bay leaves, Cilantro, Coriander, Curry leaves, Fenugreek, Gotukala, Lemongrass, Mint, Oregano, Pandan, Parsley, Rampa, Rosemary, Sage, Tarragon, Thyme Spices: All spice, Black pepper, Cardamon, Chili powder (check ingredients, sometimes has garlic added), Chipotle chili powder, Cinnamon, Cloves, Cumin, Curry powder, Fennel seeds, Five spice, Goraka, Mustard seeds, Nutmeg, Paprika, Saffron, Star anise, Turmeric Oils: Avocado oil, Canola oil, Coconut oil, Olive oil, Peanut oil, Rice bran oil, Sesame oil, Soybean oil, Sunflower oil, Vegetable oil, Garlic infused oil, Onion infused oil , Acai powder, Asafoetida powder , Baking powder, Baking soda, Cacao powder, Cocoa powder, Cream, Gelatin, Ghee, clarified butter, Icing sugar, Lard, Maca Powder, Mango Powder, Matcha Powder, Nutritional yeast, Salt, Soybean oil, Tahini, hulled

[0101] Combinations of low FODMAP and / or high FODMAP compounds may be utilized to achieve particular desired outcomes. In particular it is possible that some high FODMAP compounds may be tolerated in some people and / or if introduced gradually, and a formulation including high FODMAP compounds may be useful in such situations.

[0102] Polyphenols are an important secondary metabolite produced by plants, have attracted tremendous attention due to their health-promoting effects, including their antioxidant, antiinflammatory, antibacterial, anti-adipogenic, and neuro-protective activities, as well as health properties.

[0103] Polyphenols include but are not limited to dietary polyphenols, phenolic acids such as but not limited to benzoic acid and cinnamic acid and its derivatives, flavonoids, polyphenolic amides such as casaicinoids and avenanthramides such as but not limited to capsaicin, avenathramide, resveratrol, fisetin, and phyllanthin, other non-flavonoids such as but not limited to stilbenes and lignans.

[0104] Flavonoids include but are not limited to flavonoids, flavones, isoflavones, chaicones, flavanols, flavonols, flavanonols, quercetin, and anthocyanins.

[0105] Dietary polyphenols are derived from but not limited to blueberries, coffee, chia, cili, oat, grape, sesame, celery, grapefruit, soybean, licorice, cocoa, teas, oranges, eggplant, pineapple, walnuts, cashews, pecans, pumpkin, fruits and vegetables.

[0106] A randomized, double-blind, placebo-controlled trial showed that “a synbiotic (prebiotic + probiotic) called SIM01 modulated the gut microbiome to successfully alleviate fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and general malaise in people with Long COVID.” SIM01 contains: 20 billion colony-forming units of three bacterial strains, - bifidobacterium adolescentis (b.adolescentis), bifidobacterium bifidum (b.bifidum), and bifidobacterium longum (b. longum) three prebiotic compounds including galacto-oligosaccharides, xylo-oligosaccharides, and resistant dextrin.

[0107] While SIM01 appeared to work to some degree the ingredients are not ideal. In particular the three prebiotic compounds in SIM01 are high in Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols (FODMAP), which are short-chain carbohydrates (sugars) that are not tolerated well by some people due to lack of absorption by the small intestine.

[0108] "Gut microbiome-based multi-label machine learning accurately predicts upcoming longterm symptoms after acute COVID19." n = 707 with PACS, who were on average 5 months post-COVID-19 (Figure 1C), The top-ranked gut microbiome features for PACS include: depletion of bifidobacterium adolescentis and Roseburia hominis, pyruvate fermentation to acetate and lactate II, and enrichment of Clostridium bolteae, Flavonifractor plautii, and the urea cycle.

[0109] Only mild improvement of clinical symptoms was noted over a long period of months to year

[0110] We developed a fecal-microbiome-based multi-label machine learning model for predicting different symptoms of PACS, of which the high accuracy further reflects the finding that the gut microbiome associates with phenotypic manifestations of PACS. In line with our hypothesis, we observed that the gut microbiome explains a large part of heterogeneity in PACS. Several common biomarkers for PACS, including potential probiotics such as Bifidobacterium adolescentis, Roseburia hominis, and the bacterial pathways producing short-chain fatty acids (SCFAs).

[0111] This application describes methods and formulations that may reduce gut dysbiosis and leaky gut, that may be useful in the treatment of Irritable Bowel Syndrome (IBS), Crohn’s disease, Long CO VID and other illnesses that are caused or exacerbated by issues related to the gut microbiome.

[0112] The formula used in SIM01 appears to be helpful to those who suffer from conditions such as Long COVID, IBS, IBD, Crohn’s, etc. However, the SIM01 formula has high FODMAP components, which may not be well tolerated by many people.

[0113] We sought to develop a supplement that includes a low FODMAP prebiotic, has ingredients that promote the bacterium F. prausnitzii and Roseburia, and includes the bacterium used in SIM01, specifically Bifidobacterium adolescentis, Bifidobacterium bifidum, and Bifidobacterium longum.

[0114] Bifidobacterium adolescentis showed positive correlations with alleviation in fatigue, gastrointestinal upset, and memory loss. Bifidobacterium bifidum increases are correlated with alleviation in fatigue and general unwellness. Bifidobacterium longum correlated with an alleviation in difficulty in concentration.

[0115] The formulation described in this patent uses a low FODMAP prebiotic. Low FODMAP prebiotics include: Kiwi is a low FODMAP and has been shown in many studies to increase f. prausnitzii. To increase Roseburia this formulation may include low FODMAP prebiotics for Roseburia such as walnuts. In some embodiments the walnuts are substituted and / or augmented by other low FODMAP prebiotics for Roseburia. This is particularly useful in case of a walnut allergy. Some possible alternative prebiotics include: Partially hydrolysed guar gum (PHGG) is a low FODMAP prebiotic that increases Roseburia., potato starch, Gluten free oats, Flaxseeds, Chia seeds, Benecarios (carrot polysaccharide), Citrus pectin

[0116] One embodiment of this formulation includes, B. adolescentis, and low-histamine producers B. bifidum, and B. longum.

[0117] Many people with Long COVID have a syndrome called Mast Cell Activation Syndrome (MCAS). Use of bacteria that are low histamine producers may be helpful to avoid triggering MCAS reactions.

[0118] Other bacteria that may be included in the low histamine blend are B. longum, B. bifidum, B. lactis, L. gasseri, L. salivarius, L. rhamnosus, B. infantis, and others.

[0119] Cross-feeding between butyrate-producing and non-producing strains contributes to the production of butyrate.

[0120] Fermentation by-products from Bifidobacterium (acetate, formate, lactate and succinate) feed butyrate-producing bacteria, including Anaerostipes caccae and Roseburia intestinalis. Blautia spp. and Lactobacillus spp. are common producers of acetate and lactate, respectively, which can cross-feed butyrate producers, such as Anaerostipes spp. and Eubacterium spp. and may be included in a formulation.

[0121] One embodiment of this formulation contains: 2 parts kiwi powder, 1 part B adolescentis, 1 part low Histamine blend that includes B. Longum, B. Lactis , B. Bifidum , L. Gasseri , L. Salivarius , L. Rhamnosus or any combination of the ingredients.

[0122] Surprisingly, dramatic reduction of symptoms of Long COVID using a low FODMAP formulation of prebiotic and probiotics resolved in a matter of less than two weeks compared to all existing published literature at the time of this writing which showed only mild effects after more than 6 months of treatment.

[0123] EXAMPLES

[0124] The following example provides those of ordinary skill in the art with a description of how to make and use the subject matter disclosed herein and are not intended to limit the scope of what the inventors regard as inventive nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc.) but some experimental errors and deviations should be accounted for.

[0125] Example 1. Dosing of Subjects Having Long CO VID, Positive Outcomes

[0126] Three subjects have had a significant positive effect on Long CO VID symptoms from the following compositions provided herein:

[0127] LC-OG Composition: 1) prebiotic kiwi powder component including vitamin C, calcium, potassium, and iron; and 2) probiotic blend component of 50% Bifidobacterium adolescentis, 50% blend of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus. The ratio of the prebiotic component to the probiotic component is 1:1.

[0128] LC-02 Composition: 1) prebiotic kiwi powder component including vitamin C, calcium, potassium, and iron; and 2) probiotic blend component of 50% Bifidobacterium adolescentis, 50% blend of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus. The ratio of the prebiotic component to the probiotic component is 2:1.

[0129] Subject 1

[0130] 25 year-old female with severe Long COVID, which caused her to be bedbound. She has a history of celiac disease which has been well controlled by diet. Her symptoms included severe fatigue, for which she had to sleep approximately 16 hours a day, severe headaches that were new onset since her diagnosis and were associated with photophobia and nausea. She also had malaise, inability to listen to music or tolerate noise at times. In addition to severe fatigue (exhaustion), the subject had difficulty thinking and concentrating (brain fog), insomnia, anxiety, exercise intolerance and balance issues. She was diagnosed with POTS on autonomic testing. The subject was unable to do activities of daily living, including that she was unable to feed herself at times because of weakness and confusion and was also unable to bathe herself. This subject had post-exertional malaise crashes every day to every other day in which she would lose the ability to speak (aphasia) and the ability to move. Within 10 days of starting the LC-OG synbiotic, the subject was no longer having crashes which she indicates has been life changing. With pacing, she was able to go out in a wheelchair and socialize with a friend for 2 to 3 hours without crashing which was an unexpected, significant change. She was now able to read a book and could watch TV for one hour without becoming severely fatigued. She was not as sensitive to light and sound and noted that she could think more clearly. The subject is now able to reheat a meal on her own and can feed herself. The subject went from having severe PEM crashes every day to every other day, to only having a milder PEM crash about once every 2 to 3 months.

[0131] The subject was later switched to LC-02 synbiotic and has done well on this formula with minimal post-exertional malaise symptoms, improved cognition, and improved fatigue. Migraine headaches have improved and she needs to have Botox injections for severe migraine less often. She still has limited exercise tolerance, but states that the improvement that she has had since she started the LC-OG and LC-02 synbiotics has been life changing.

[0132] Subject 2

[0133] Male in his late 20s, considered a strong study subject by doctor because he had Long CO VID as a single diagnosis with no other medical comorbidities. He was a healthy, active man until he became ill with CO VID and then his health declined. Symptoms included brain fog (memory loss and difficulty in concentration), severe fatigue, occasional shortness of breath and exercise intolerance. In addition, he noted pain in his chest, joints and muscles, as well as gastrointestinal symptoms of diarrhea, constipation, irritable bowel pain symptoms and acid reflux. He started the LC-OG synbiotic as a monotherapy because he wanted to try one treatment protocol at a time to best assess what worked for him. The subject states that since starting the LC-OG synbiotic, all of his Long COVID symptoms have improved including remission of brain fog symptoms, improved energy levels and an overall feeling of wellness, as well as normalized gut symptoms.

[0134] Subject 3

[0135] 28 year-old female with Long CO VID who had symptoms of severe fatigue, difficulty in concentration (brain fog), malaise, unrefreshing sleep, hair loss, anxiety, exercise intolerance, joint and muscle pain, and gastrointestinal issues including constipation, abdominal pain, nausea, vomiting and bloating. She had post-exertional malaise (PEM) crashes 5 times weekly and only tolerated being upright for 2 hours per day. After being on the LC-OG synbiotic, she did not notice a large difference in her symptoms. But her responses on a questionnaire showed that all of her symptoms had improved 1 to 2 points after just 2 weeks of taking LC-OG. For example, she rated difficulty in concentration as a 7 on a 10 point scale initially, but it was down to a 5 within 2 weeks of being on LC-OG. She stated that she was now able to be upright for 12 hours per day, instead of 2 hours. Her PEM crashes also decreased in frequency to 4 times per week.

[0136] The subject also noted that LC-OG was the first probiotic that did not cause mast cell activation syndrome (MCAS) symptoms. She wrote “this is the first probiotic that I’ve taken that did not cause adverse reactions”.

[0137] LC-OG and LC-02 6 contain 6 histamine-reducing probiotics and 1 histamine neutral probiotic which may be why MCAS symptoms were better on these formulas.

Claims

What is claimed is:

1. A composition for enhancing gut health and alleviating symptoms associated with gut dysbiosis, comprising:a prebiotic component comprising one or more prebiotics; anda probiotic component comprising one or more probiotics.

2. The composition of claim 1 wherein the one or more prebiotics are selected from the group consisting of Acai berries, Acai berry powder, Acai berry extract, Acacia fiber, Acerola cherry powder, Acerola cherry extract, Agave inulin, Almond butter, Almond powder, Almond extract, Almonds, Amla powder, Amla extract, Apple pectin, Apple powder, Apple extract, Arabinogalactan, Artichoke extract, Artichokes, Ashwagandha powder, Ashwagandha extract, Asparagus, Bacillus coagulans, Bamboo shoots, Banana powder, Banana extract, Bananas, Baobab powder, Baobab extract, Barley, Beans, Beets, Benecaries, Berries, Beta-glucan, Betel nut powder, Betel nut extract, Bilberries, Bilberry powder, Bilberry extract, Black currant powder, Black currant extract, Black currants, Blackberries, Blackberry powder, Blackberry extract, Blueberries, Blueberry powder, Blueberry extract, Brazil nut butter, Brazil nut powder, Brazil nut extract, Broccoli, Broccoli powder, Broccoli extract, Burdock root, Burdock root extract, Butternut powder, Butternut extract, Cacao butter, Cacao powder, Cacao extract, Cacao nibs, Cashew butter, Cashew powder, Cashew extract, Cashews, Celeriac, Celery, Cellulose, Cherries, Cherry extract, Cherry powder, Chia seeds, Chicory root, Chicory root extract, Citrus fruits, Citrus pectin, Citrus extract, Coconut butter, Coconut powder, Coconut extract, Coconut water, Coconuts, Coffee cherry powder, Coffee cherry extract, Cranberries, Cranberry powder, Cranberry extract, Dandelion greens, Dandelion extract, Date powder, Date extract, Dates, Elderberries, Elderberry powder, Elderberry extract, Fennel, Fennel extract, Fenugreek, Fenugreek extract, Flaxseeds, Flaxseed extract, Fructooligosaccharides (FOS), Galactomannans, Galactooligosaccharides (GOS), Garlic, Garlic, Garlic extract, Glucomannan, Goji berries, Goji berry powder, Goji berry extract, Grape powder, Grape extract, Grapes, Grapefruit, Grapefruit pectin, Grapefruit extract, Green peas, Green tea, Green tea powder, Green tea extract, Guar gum, Partially hydrolyzed guar gum, Guava, Guava powder, Guava extract, Hazelnut, Hazelnut butter, Hazelnut powder, Hazelnut extract, Hazelnuts, Honey, Human milk oligosaccharides (HMO), Inulin, Isomaltooligosaccharides (IMO), Jerusalem artichoke, Jerusalem artichoke extract, Kale,Kale powder, Kale extract, Karaya gum, Kefir, Kiwi, Kiwi powder, Kiwi extract, Kombucha, Konjac root, Konjac root extract, Lactulose, Lentils, Leeks, Locust bean gum, Macadamia nut butter, Macadamia nut powder, Macadamia nut extract, Macadamia nuts, Maqui berry powder, Maqui berry extract, Matcha powder, Matcha extract, Milk, Mulberry powder, Mulberry extract, Mushrooms, Oat bran, Oats, Okra, Onion powder, Onion extract, Onions, Orange powder, Orange extract, Oranges, Pecan butter, Pecan powder, Pecan extract, Pecans, Pectin, Papaya powder, Papaya extract, Papayas, Parsley, Pecan nut butter, Pectin, Peas, Pineapple powder, Pineapple extract, Pineapples, Pistachio butter, Pistachio powder, Pistachio extract, Pistachios, Plantain, Pomegranate powder, Pomegranate extract, Pomegranates, Potato starch, Psyllium husk, Pumpkin, Pumpkin powder, Pumpkin extract, Pumpkin seeds, Radish, Raffinose, Rhubarb, Rhubarb extract, Rye, Salsify, Sauerkraut, Shallots, Soybeans, Spinach, Spinach powder, Spinach extract, Stachyose, Starch, Strawberries, Strawberry powder, Strawberry extract, Sunflower seeds, Sweet potatoes, Tamarind gum, Tamarind extract, Turmeric powder, Turmeric extract, Turnips, Verbascose, Walnut butter, Walnut powder, Walnut extract, Walnuts, Wheat bran, Whole wheat bread, Xanthan gum, Xylooligosaccharides (XOS), Yacon syrup, Yeast beta-glucan, Yogurt, and combinations of any of the foregoing.

3. The composition of claim 1 or claim 2, wherein the prebiotic component is selected from kiwi powder, walnut powder, partially hydrolysed guar gum, and combinations of any of the foregoing.

4. The composition of any one of claims 1 - 3, wherein the one or more probiotics are selected from the group consisting of Anaerostipes caccae, Anaerostipes hadrus, Aspergillus niger, Aspergillus oryzae, Bacillus clausii, Bacillus coagulans, Bacillus licheniformis, Bacillus subtilis, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium intestinalis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium scardovii, Blautia hansenii, Blautia luti, Blautia obeum, Blautia producta, Blautia schitovskii, Blautia wexlerae, Butyrivibrio alvinus, Butyrivibrio crossotus, Butyrivibrio fibrisolvens, Butyrivibrio hungatei, Butyrivibrio lipocalidus, Butyrivibrio matronii, Butyrivibrio parvus, Butyrivibrio phytoremedians, Butyrivibrio plebeius, Butyrivibrio proteoclasticus, Butyrivibrio pseudofibrisolvens, Butyrivibrio straminisolvens, Butyrivibrio vermis,Butyrivibrio xylanivorans, Clostridium butyricum, Clostridium perfringens, Coprococcus catus, Coprococcus comes, Enterococcus faecalis, Enterococcus faecium, Escherichia coli (E. coli), Eubacterium biforme, Eubacterium brachy, Eubacterium cellulosolvens, Eubacterium combesii, Eubacterium coprostanoligenes, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium eligens, Eubacterium hallii, Eubacterium hadrum, Eubacterium incestum, Eubacterium limosum, Eubacterium minutum, Eubacterium multiforme, Eubacterium nitritogenes, Eubacterium nodatum, Eubacterium pexum, Eubacterium rectale, Eubacterium ruminantium, Eubacterium saburreum, Eubacterium siraeum, Eubacterium tenue, Eubacterium tortuosum, Eubacterium uniforme, Eubacterium ventriosum, Eubacterium xylanophilum Faecalibacterium prausnitzii, Faecalibacterium pseudoprausnitzii, Lactobacillus acidophilus, Lactobacillus agilis, Lactobacillus alimentarius, Lactobacillus aviarius, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus gallinarum, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus lactis, Lactobacillus mucosae, Lactobacillus panis, Lactobacillus pentosus, Lactobacillus plantarum, Lactobacillus psittaci, Lactobacillus pullorum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus ruminis, Lactobacillus saerimneri, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus sharpeae, Lactobacillus suebicus, Lactococcus cremoris, Lactococcus lactis, Leuconostoc lactis, Leuconostoc mesenteroides, Megasphaera elsdenii, Mitsuokella jalaludinii, Odoribacter splanchnicus, Pediococcus acidilactici, Pediococcus pentosaceus, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Saccharomyces boulardii, Saccharomyces cerevisiae, Streptococcus thermophilus, and combination of any of the foregoing.

5. The composition of any one of claims 1-4, wherein the probiotic component comprises Bifidobacterium adolescentis and a blend of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus gasseri, Lactobacillus salivarius, and Lactobacillus rhamnosus.

6. The composition of claim 5, wherein the probiotic component comprises 50% Bifidobacterium adolescentis and 50% of the blend.

7. The composition of claim 5 or claim 6, wherein the ratio of the prebiotic component to the probiotic component is 1:1.

8. The composition of claim 5 or claim 6, wherein the ratio of the prebiotic component to the probiotic component is 2:1.

9. The composition of any one of claims 1-8, wherein the prebiotic is an ingredient to supplement the population of Faecalibacterium prausnitzii (F. prausnitzii);10. The composition of any one of claims 1-9, wherein the prebiotic is low FODMAP.

11. The composition of any one of claims 1-10, wherein the prebiotic or prebiotics are combined with the probiotic in a volume at a multiple > 0 and less than or equal to 1, or > 1 and less than or equal to 2, or > 2 and less than or equal to 3, or > 3 and less than or equal to 4, or greater than 4.

12. The composition of any one of claims 1-11, which is formulated for oral administration.

13. The composition of claim 12, wherein the composition is in the form of a powder, a capsule, a tablet, a chewable dosage form, or a gummy dosage form.

14. The composition of claim 13, wherein the tablet is formulated with an enteric coating.

15. The composition of any one of claims 1-11, which is formulated in a rectal suppository or an enema.

16. The composition of any one of claims 1-11, which is formulated for sublingual administration.

17. The composition of claim 13, wherein the powder is administered dissolved in an aqueous fluid, or wherein the powder is combined into a paste or gel prior to administration, or wherein the powder is included with food prior to ingestion.

18. The composition of any one of claims 1-17, further comprising one or more excipients selected from the group consisting of starch, potato starch, corn starch, oat bran, cellulose, guar gum, pectin, a low FODMAP excipient, or combinations thereof.

19. A method of treating gut dysbiosis and / or one or more symptoms thereof, comprising administering a composition according to any one of claims 1-18 to a subject in need thereof.

20. The method of claim 19, wherein the composition ameliorates one or more symptoms associated with conditions associated with low levels of F. prausnitzii or Roseburia.

21. The method of claim 20, wherein the symptoms are selected from the group consisting of ME / CFS, Crohn’s disease, ulcerative colitis, celiac disease, leaky gut, gut dysbiosis, gastrointestinal upset, Long COVID, fatigue, depression, brain fog, cognitive dysfunction, difficulty in concentration, memory loss, and combinations of any of the foregoing.

22. The method of any one of claims 19-21, wherein the composition increases butyrate production in the gut of the subject.

23. The method of any one of claims 19-22, wherein the composition improves colonocyte function and restores and maintains gastrointestinal tract integrity.

24. The method of any one of claims 19-23, wherein the composition ameliorates one or more symptoms of Long COVID, wherein the symptoms are selected from the group consisting of fatigue, gastrointestinal upset, memory loss, difficulty in concentration, and combinations thereof.

25. The method of any one of claims 19-24, wherein the composition is administered to the subject once daily, twice daily, three times daily, four times daily, five times daily, six times daily, every other day, every two days, every three days, every four days, every 5 days, every 6 days, once a week, once every two weeks, once every three weeks, once every four weeks, or once a month.

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