Bacillus amyloliquefaciens strains art12 and art24 for the treatment of disorders of the CNS

Abstract

Disclosed herein are compositions, methods, and kits for preventing, ameliorating, or treating Multiple Sclerosis (MS), Autism Spectrum Disorder (ASD) and / or social anxiety, a tauopathy, Huntington's Disease (HD), or amyotrophic lateral sclerosis (ALS), and / or reducing the severity of one or more risk factors, signs, or symptoms associated with MS, ASD and / or social anxiety, a tauopathy, HD, or ALS. In particular, the technology of the present disclosure relates to methods for administering an effective amount of a composition comprising one or more strains of an operational group Bacillus amyloliquefaciens bacteria identified as ART24 and ART12, to a subject suffering from or at risk for MS, ASD and / or social anxiety, a tauopathy, HD, or ALS.

Description

BACILLUS AMYLOLIQUEFACIENS STRAINS ART12 AND ART24 FOR THE TREATMENT OF DISORDERS OF THE CNSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 452,948, filed March 17, 2023, U.S. Provisional Application No. 63 / 455,339, filed March 29, 2023, U.S. Provisional Application No. 63 / 509,996, filed June 23, 2023, U.S. Provisional Application No. 63 / 510,000, filed June 23, 2023, and U.S. Provisional Application No. 63 / 593,760, filed October 27, 2023, the contents of each of which are incorporated herein by reference in their entirety for any and all purposes.TECHNICAL FIELD

[0002] The present technology relates generally to methods and compositions for preventing, ameliorating, or treating Multiple Sclerosis (MS), Autism Spectrum Disorder (ASD) and / or social anxiety, tauopathies, Huntington’s Disease (HD), and amyotrophic lateral sclerosis (ALS), and / or reducing the severity of one or more risk factors, signs, or symptoms associated with these conditions. In particular, the present technology relates to administering an effective amount of a composition comprising one or more strains of an operational group Bacillus amyloliquefaciens bacteria, identified as ART24 and / or ART12, to a subject suffering from or at risk for MS, ASD and / or social anxiety, a tauopathy, HD, or ALS.BACKGROUND

[0003] The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art to the compositions and methods disclosed herein.

[0004] Multiple sclerosis (MS) is a nervous system disease of the brain and spinal cord that damages the myelin sheath coating on neurons. This damage results in impaired neuronal signaling with numerous downstream impacts including muscle weakness, loss of coordination and balance, painful or numbing sensations, and cognitive impairment. The condition affects approximately one million people in the United States alone, and is considered the most common demyelinating disease. MS includes four subtypes classifiedas clinically isolated syndrome, relapsing remitting MS, primary progressive MS, and secondary progressive MS.

[0005] The exact cause of MS is not fully understood, rendering diagnosis challenging. Additionally, there is no cure for the condition and there are limited treatment options currently available. As such, there is a significant need for novel approaches to treating MS.

[0006] Autism spectrum disorder (ASD) is the most commonly diagnosed neurodevelopmental disorder, with current estimates of more than 1% of affected children across nations. The condition affects approximately 1 in 45 children in the United States alone. Autism Spectrum Disorder includes three separably diagnosable conditions: autistic disorder, pervasive developmental disorder not otherwise specified, and Asperger syndrome. The patients form a highly heterogeneous group with only the behavioral phenotype in common. A few genetic markers for risk of ASD have been identified, but the vast majority of cases do not have a clear genetic linkage. Common symptoms, which are used to diagnose ASD via diagnostic systems such as questionnaires or surveys, include impaired social communication and interaction skills, restricted or repetitive behaviors or interests, delayed development of language skills, delayed development of movement skills, delayed development of cognitive or learning skills, hyperactive, impulsive, or inattentive behavior, epilepsy, seizures, gastrointestinal diseases or disorders, anxiety, excessive fear or fearlessness, or any combination thereof.

[0007] Social anxiety is a common mental health disorder, wherein subjects experience varying levels of enhanced anxiety regarding social interactions. In extreme cases, such as clinically diagnosed social anxiety disorder, subjects can experience nausea and panic attacks. Treatments for social anxiety exist, but many have varied efficacy and undesirable side effects.

[0008] There is currently no cure for ASD and there are no therapeutics approved to treat the core symptoms of ASD. Additionally, there are significant limitations to many of the currently approved therapeutics for treating social anxiety. As such, there is a significant need for novel approaches to treating ASD and social anxiety.

[0009] Tauopathies is an umbrella term encompassing a number of disorders that are characterized by Tau deposits in the brain. Mutations to the microtubule associated protein Tau (MAPT) gene that encodes Tau can lead to pathogenic isoforms 3R and 4R and deposits that are made up of 3R, 4R, or a mix therein. Tau deposits can occur in multiple locations, including neurons, glial cells, and extracellular space. Tauopathies are further characterized by neurodegeneration and symptoms of dementia, personality changes, social behavioral issues, psychiatric symptoms, language issues, and reduced balance and coordination.

[0010] At least 26 different tauopathies have been identified, most of which lack effective treatment options. For example, dementia afflicts more than 55 million people worldwide but there are limited treatment options available and no cure. While many mutations that cause Tau aggregation have been identified, the mechanism of pathogenesis is still uncertain, as is the degree to which Tau aggregation impacts pathogenesis in different tauopathies. Accordingly, there is a significant need for novel approaches to treating tauopathies broadly.

[0011] Huntington’s Disease (HD) is a neurodegenerative, autosomal dominant genetic disease caused by a mutation to the huntingtin gene (HTT). HD is mostly found in those of European descent, and estimates of disease prevalence range from 4 in 100,000 to 9 in 100,000. The HTT gene contains a variable number of CAG trinucleotide repeats encoding a polyglutamine tract. Less than 27 CAG repeats is classified as a normal level with no risk of disease. Between 27 and 35 repeats is considered an intermediate level with elevated risk of disease to an individual’s offspring, but no disease risk to the individual. Between 36 and 39 repeats is classified as reduced penetrance, with a risk of disease to the individual and to their offspring. Greater than 40 repeats is considered full penetrance, meaning the individual will have HD and any offspring will have a risk of the disease. The mutated HTT protein with an elongated polyglutamine tract is prone to cleavage and aggregation in neurons, forming inclusion bodies that interfere with neuronal activity and cause cell death. As HD progresses, increasing neuronal interference and cell death cause the symptoms associated with HD, including diminished cognitive function, memory loss, chorea, sudden mood swings, and death.

[0012] There is no cure for HD, and there are currently limited treatment options for managing the symptoms associated with the disease. Only tetrabenazine and deutetrabenzaine are approved in the United States, and both drugs treat the involuntary jerking and writhing motions (chorea) associated with HD. Antidepressants, moodstabilizing drugs, and antipsychotics are also commonly prescribed to treat psychiatric disorders associated with HD. Ultimately, none of these treatments slow disease progression or prevent neurodegeneration and death. Accordingly, there is a significant need for novel approaches to treating HD.

[0013] Amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease) is a fatal, progressive neuromuscular condition characterized by both lower motor neuron and upper motor neuron degeneration, leading to diffuse muscle weakness and spasticity. Although clinical presentations can vary, as ALS progresses, patients lose the use of their limbs, develop dysarthria and dysphagia, and most commonly die from respiratory failure. ALS is estimated to affect about 18,000 people in the United States at any given time. The annual prevalence of the condition in the U.S. is about four to six per 100,000 people. Nearly all cases of ALS are sporadic and idiopathic. Only about 5-10% of all ALS cases are due to identified genetic mutations. While a great deal has been learned about the pathophysiology of ALS and efforts have been made to improve multidisciplinary care, the average survival from the time of diagnosis remains only 3-5 years.

[0014] There is no cure for ALS. Accordingly, there is a need to develop novel approaches to treating this condition.SUMMARY

[0015] In one aspect, the present disclosure provides a method for treating, ameliorating, or preventing a disease selected from the group consisting of: multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, and amyotrophic lateral sclerosis, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising one or more bacterial strains selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088). In some embodiments, thecomposition further comprises a preservative. In some embodiments, the preservative is a cryoprotectant. In some embodiments, the cryoprotectant is selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide. In some embodiments, the cryoprotectant is selected from the group consisting of inosine-5'- monophosphate (IMP), guanosine-5 '-monophosphate (GMP), adenosine-5 '-monophosphate (AMP), uranosine-5 '-monophosphate (UMP), cytidine-5 '-monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, and skim milk. In some embodiments, the cryoprotectant comprises trehalose. In some embodiments, the bacterial strain is lyophilized. In some embodiments, the bacterial strain is in the form of a spore. In some embodiments, the subject is administered the composition at a regular or irregular interval. In some embodiments, the subject is administered the composition daily, weekly, or monthly. In some embodiments, the subject is administered the composition twice a day. In some embodiments, the composition is administered orally, sublingually, buccaly, or rectally. In some embodiments, the composition is administered enterically. In some embodiments, the method further comprises administering a co-therapeutic to the subject. In some embodiments, the co-therapeutic is administered simultaneously or sequentially with the composition comprising a bacterial strain. In some embodiments, the composition comprises ART12. In some embodiments, the composition comprises ART24. In some embodiments, the composition comprises ART12 and ART24. In some embodiments, the method further comprises evaluating the subject’s symptom severity before composition administration and evaluating the subject’s symptom severity after the composition has been administered at least once. In some embodiments, the subject exhibits improved or reduced symptoms after administration of the composition. In some embodiments, the subject is asymptomatic and is at elevated risk of multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, or amyotrophic lateral sclerosis. In some embodiments, the subject exhibits a delay in onset multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, and amyotrophic lateral sclerosis after administration of the composition. In some embodiments, the composition further comprises a pharmaceutically appropriate excipient. In some embodiments, the disease is multiple sclerosis. In some embodiments, the diseaseis autism spectrum disorder and / or social anxiety. In some embodiments, the disease is a tauopathy. In some embodiments, the disease is Huntington’s Disease. In some embodiments, the disease is amyotrophic lateral sclerosis.

[0016] In one aspect, the present disclosure provides a kit for use in treating a disease selected from the group consisting of: multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, and amyotrophic lateral sclerosis comprising: (a) a composition comprising a bacterial strain selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088); and (b) a package insert with instructions for treating multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, or amyotrophic lateral sclerosis in a subject in need thereof. In some embodiments, the instructions indicate that the bacterial strain is administered to the subject twice daily. In some embodiments, the insert further instructs that the bacterial strain be administered orally. In some embodiments, the insert further instructs that the subject’s symptoms are tracked during the period of treatment. In some embodiments, the concentration of the bacterial strain is about IxlO8CFU / ml bacteria to about IxlO14CFU / ml bacteria. In some embodiments, the insert further instructs that the subject be administered about IxlO9CFU to about IxlO14CFU of the bacterial strain per day. In some embodiments, the composition comprising the bacterial strain is formulated for oral administration. In some embodiments, the kit further comprises a co-therapeutic.BRIEF DESCRIPTION OF THE DRAWINGS

[0017] FIG. 1 is a schematic of the experimental design used to study the therapeutic potential of ART12 and ART24 in the experimental allergic encephalomyelitis (EAE) model of Multiple Sclerosis in mice. In the top panel, the row labeled “A” designates Dosing FTY20 (Positive control), the row labeled “B” designates Dosing (Groups 2 and 4- 5), and the row labeled “C” designates Body Weight + Clinical signs.

[0018] FIG. 2 is a graph of the average EAE Clinical Scoring for each treatment group from study day 0 through study day 24. # p<0.05 compared to treatment group 2 (vehicle), ### p<0.001 compared to treatment group 2 (vehicle), and #### p<0.0001 compared totreatment group 2 (vehicle). All statistics performed using a one-way ANOVA followed by Dunnett’ s test.

[0019] FIG. 3 is a bar graph of the average Motor Evoked Potential (MEP) duration (milliseconds) for treatment groups 1-5 at study day 12 and study day 24, and the baseline MEP duration pre-treatment group assignment at study day 0. * p<0.05 compared to baseline, **** pO.OOOl compared to baseline, $$ p<0.01 compared to treatment group 1 (naive), and ### p<0.001 compared to treatment group 2 (vehicle). All statistics performed using a one-way ANOVA followed by Dunnett’ s test.

[0020] FIG. 4 is a bar graph of the average MEP number of sub-peaks for treatment groups 1-5 at study day 12 and study day 24, and the baseline MEP number of sub-peaks pre-treatment group assignment at study day 0. * p<0.05 compared to baseline, **** p<0.0001 compared to baseline, $ p<0.05 compared to treatment group 1 (naive), and ## p<0.01 compared to treatment group 2 (vehicle). All statistics performed using a one-way ANOVA followed by Dunnett’ s test.

[0021] FIG. 5 is a picture of the 3-chamber test structure that was used to test the social behavior of the different mouse treatment groups.

[0022] FIGS. 6A-6B are bar graphs of sociability test results in terms of average seconds spent by each test condition group exploring a stimulus mouse (Cong) or an object (Obj) (Mean + / - SEM). FIG. 6A is a graph of exploration time from the first five minutes in the 3-chamber test, and FIG. 6B is a graph of exploration time from the first ten minutes in the 3-chamber test. Statistics comparing results within a test condition group were performed using a paired Student’s t-test. Statistics comparing results between test condition groups were performed using an unpaired Student’s t-test, * p<0.05 compared to C57-Control and *** p<0.001 compared to C57-Control.

[0023] FIGS. 7A-7B are bar graphs of sociability test results in terms of average percent of time spent by each test condition group exploring the stimulus (congener) mouse (Mean + / - SEM). FIG. 7A is a graph of the percent of time spent exploring the stimulus mouse from the first five minutes in the 3-chamber test, and FIG. 7B is a graph of the percent of time spent exploring the stimulus mouse from the first ten minutes in the 3-chamber test.Statistics comparing test condition group results to a 50% baseline were performed using a paired Student’s t-test. Statistics comparing results between test condition groups were performed using an unpaired Student’ s t-test.

[0024] FIGS. 8A-8B are bar graphs of social novelty test results in terms of average seconds spent by each test condition group exploring a new stimulus mouse (Novel) or a familiar stimulus mouse (Famil) (Mean + / - SEM). FIG. 8A is a graph of exploration time from the first five minutes in the 3-chamber test, and FIG. 8B is a graph of exploration time from the first ten minutes in the 3-chamber test. Statistics comparing results within a test condition group were performed using a paired Student’ s t-test. Statistics comparing results between test condition groups were performed using an unpaired Student’s -test, * p<0.05 compared to C57-Control, ** p<0.01 compared to C57-Control, and *** p<0.001 compared to C57-Control.

[0025] FIGS. 9A-9B are bar graphs of sociability test results in terms of percent of time spent by each test condition group exploring the novel stimulus (congener) mouse (Mean + / - SEM). FIG. 9A is a graph of the percent of time spent exploring the novel stimulus mouse from the first five minutes in the 3-chamber test, and FIG. 9B is a graph of the percent of time spent exploring the novel stimulus mouse from the first ten minutes in the 3- chamber test. Statistics comparing test condition group results to a 50% baseline were performed using a paired Student’s t-test. Statistics comparing results between test condition groups were performed using an unpaired Student’s t-test.

[0026] FIG. 10 is a bar graph of the average distance traveled by each test condition group during the three phases of the 3-chamber experiment: habituation, sociability, and social novelty. Statistics comparing results between test condition groups were performed using an unpaired Student’s t-test, * p<0.05 compared to C57-Control and *** p<0.001 compared to C57-Control.

[0027] FIG. 11 is a graph of the relative fold change in average reactive oxygen species (ROS) production in the brain between the different treatment groups, with wild type (WT) treated as the baseline. **** p<0.0001 compared to tauopathy model. All statistics performed using a one-way ANOVA with post-hoc Turkeys test.

[0028] FIG. 12 is a graph of the average total swimming distance of the different treatment groups. **** p<0.0001 compared to tauopathy model. All statistics performed using a one-way ANOVA with post-hoc Turkeys test.

[0029] FIG. 13 is a graph of the average number of involuntary jerk movements per minute for each study group. Wild type (WT), Huntington’s Disease model fish (mHD), tetrabenazine-treated mHD fish (Tetrabenazine), ART 12-treated mHD fish (ART12), ART 24-treated mHD fish (ART24), and ART 12- and ART 24-treated mHD fish (ART12 / 24). **** p<o 0001 compared to mHD. All statistics performed using a one-way ANOVA with post-hoc Turkeys test.

[0030] FIG. 14 is a chart showing the operculum movement per minute for each treatment group, which are listed along the x-axis from left to right as follows: WT; TDP43- / - ALS model; Riluzole (lOpM); ADS024 (2E7 TCC / ml); ADS012 (2E7 TCC / ml); ADS024 (1E7 TCC / ml) + ADS012 (1E7 TCC / ml); and ADS024 (2E7 TCC / ml) + ADS012 (2E7 TCC / ml).

[0031] FIG. 15 is a chart showing the buccal movement per minute for each treatment group, which are listed along the x-axis from left to right as follows: WT; TDP43- / - ALS model; Riluzole (lOpM); ADS024 (2E7 TCC / ml); ADS012 (2E7 TCC / ml); ADS024 (1E7 TCC / ml) + ADS012 (1E7 TCC / ml); and ADS024 (2E7 TCC / ml) + ADS012 (2E7 TCC / ml).DETAILED DESCRIPTION

[0032] It is to be appreciated that certain aspects, modes, embodiments, variations and features of the present technology are described below in various levels of detail in order to provide a substantial understanding of the present technology. The definitions of certain terms as used in this specification are provided below. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this present technology belongs.I. Definitions

[0033] The following terms are used herein, the definitions of which are provided for guidance.

[0034] As used herein, the singular forms “a,” “an,” and “the” designate both the singular and the plural, unless expressly stated to designate the singular only.

[0035] The term “about” and the use of ranges in general, whether or not qualified by the term about, means that the number comprehended is not limited to the exact number set forth herein, and is intended to refer to ranges substantially within the quoted range while not departing from the scope of the present technology. As used herein, “about” will be understood by persons of ordinary skill in the art and will vary to some extent on the context in which it is used. If there are uses of the term which are not clear to persons of ordinary skill in the art given the context in which it is used, “about” will mean up to plus or minus 10% of the particular term.

[0036] As used herein, “administration” of an agent, drug, bacterial strain(s) or spore thereof, or composition of the present technology to a subject includes any route of introducing or delivering to a subject a compound to perform its intended function. Administration can be carried out by any suitable route, including orally, intranasally, parenterally (intravenously, intramuscularly, intraperitoneally, or subcutaneously), topically, or by inhalation. In some embodiments, the compositions of the present technology are formulated for enteric administration. In some embodiments, the compositions are formulated for oral, sublingual, buccal, or rectal delivery. In some embodiments, the compositions are formulated for use as a probiotic. In some embodiments, the compositions are formulated for use as a live biotherapeutic. As used herein, administration includes self-administration and administration by another.

[0037] As used herein, “ART12” or “ADS012” refers to a bacterial strain, or spore thereof, having been deposited under NCIMB Accession No. 43087, or compositions comprising the strain. ART12 is considered a member of an “operational group B. amyloliquefaciens” that comprises the soil-borne B. amyloliquefaciens, and plant associated Bacillus siamensis and Bacillus velezensis.

[0038] As used herein, “ART24” or “ADS024” refers to a bacterial strain, or spore thereof, having been deposited under NCIMB Accession No. 43088, or compositions comprising the strain. ART24 is considered a member of an “operational group B.amylohquefctcien " that comprises the soil-borne B. amyloliquefaciens, and plant associated Bacillus siamensis and Bacillus velezensis.

[0039] As used herein, the term a “course of therapy” refers to a treatment intervention that uses a form of interpersonal therapy as a treatment of a disease or disorder. For example, a course of therapy for Autism Spectrum Disorder could include talk therapy, discrete trial training, pivotal response training, speech and language therapy, occupational therapy, sensory integration therapy, physical therapy, social-relational training, or cognitive-behavior therapy. A course of therapy for a subject with ASD can assist the subject in managing symptoms associated with ASD. The skilled artisan will appreciate the range of appropriate treatment interventions that can be included within a course of therapy for a particular disease or disorder, such as Autism Spectrum Disorder.

[0040] As used herein, the terms “effective amount,” or “therapeutically effective amount,” and “pharmaceutically effective amount” refer to a quantity sufficient to achieve a desired therapeutic and / or prophylactic effect, e.g., an amount which results in the prevention of a disease, condition, and / or symptom(s) thereof. In the context of therapeutic or prophylactic applications, the amount of a composition administered to the subject will depend on the type and severity of the disease and on the characteristics of the subject, such as general health, age, sex, body weight, and tolerance to the composition drugs. It will also depend on the degree, severity, and type of disease or condition. The skilled artisan will be able to determine appropriate dosages depending on these and other factors. In some embodiments, multiple doses are administered. Additionally or alternatively, in some embodiments, multiple therapies, therapeutic compositions, or compounds (e.g., pharmaceutical compositions comprising multiple bacterial strains alone or in combination with additional active agents, such as: disease modifying agents; or pharmaceutical compositions comprising multiple bacterial strains alone or in combination with additional therapeutics, such as a course of therapy; or pharmaceutical compositions comprising multiple bacterial strains alone or in combination with additional active agents such as cooccurring symptom therapeutics; or anti-Tau antibodies, vaccines inducing immunity against tau, tau-disaggregation agents, anti-tau-expression agents, anti-amyloid plaque agents, anti-amyloid antibodies, modulators of Tau phosphorylation, modulators of Tau acylation, histone deacetylase inhibitors, modulators of Tau glycosylation, inhibitors of Tauglycosylation, modulators of Tau truncation, proteasome stimulators, USP14 inhibitors, phosphodiesterase inhibitors, autophagy activators, chaperone modulators, co-chaperone modulators, and Tau oriented multi -target directed ligands; or olanzapine, pimozide, risperidone, fluphenazine, tetrabenazine, deuterabenazine, amantadine, levetiracetam, clonazepam, haloperidol, aripiprazole, quetiapine, citalopram, escitalopram, fluoxetine, sertraline, divalproex, carbamazepine, lamotrigine, antipsychotics, antidepressants, anticonvulsants, mood-stabilizing drugs, and anti-anxiety agents) are administered.

[0041] In some embodiments, in the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject having one or more signs, symptoms, or risk factors of Multiple Sclerosis, including, but not limited to fatigue, dysesthesia, difficulty walking, numbness, tingling, spasticity, weakness, vision problems, vertigo, dizziness, bladder problems, bowel problems, sexual problems, pain and itching, cognitive function changes, emotional changes, depression, elevated levels of antibodies against myelin basic protein (MBP), myelin oligodendrocytic glycoprotein (MOG), Epstein Barr virus, ganglioside and / or neurofilaments, inflammation of the immune system, demyelination of neurons, impaired electrophysiology, elevated kappa free light chain abundance in cerebrospinal fluids, and / or lesions on the brain or spinal cord. For example, a “therapeutically effective amount” of the compositions of the present technology, includes levels at which the presence, frequency, or severity of one or more signs, symptoms, or risk factors of MS are, at a minimum, ameliorated. In some embodiments, a therapeutically effective amount reduces or ameliorates the physiological effects of MS, and / or the risk factors of MS, and / or the likelihood of developing MS. In some embodiments, a therapeutically effective amount increases the time between symptomatic episodes and decreases the severity of symptoms during an episode. In some embodiments, a therapeutically effective amount is achieved by multiple administrations. In some embodiments, a therapeutically effective amount is achieved with a single administration.

[0042] In some embodiments, in the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject having one or more signs, symptoms, or risk factors of ASD, including, but not limited to, impaired social communication and interaction skills (e.g., a lack of eye contact,lack of responsiveness to name, lack of facial expressions, failure to interact with others, failure to make hand gestures, failure to react to the emotions of other, or any combination thereof), restricted or repetitive behaviors or interests, delayed development of language skills, delayed development of movement skills, delayed development of cognitive or learning skills, hyperactive, impulsive, or inattentive behavior, epilepsy, seizures, gastrointestinal diseases or disorders, anxiety, excessive fear or fearlessness, or any combination thereof In the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject who is diagnosed with ASD using a diagnostic system or a subject who would be diagnosed with ASD by a diagnostic system if it were applied. Appropriate diagnostic systems include, but are not limited to, Childhood Autism Rating Scale (CARS), Childhood Autism Rating Scale 2 - Standard Form (CARS2-ST), Childhood Autism Rating Scale 2 - High Functioning (CARS2-ST), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Vineland Adaptive Behavior Scale II (VABS-II), Autism Diagnosis Interview (ADI-R), Autism Diagnostic Observation Schedule - Generic (ADOS- G), Gilliam Autism Rating Scale - Second Edition (GARS-2), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). For example, a “therapeutically effective amount” of the compositions of the present technology, includes levels at which the presence, frequency, or severity of one or more signs, symptoms, or risk factors of ASD are, at a minimum, ameliorated. In some embodiments, a therapeutically effective amount reduces or ameliorates the physiological effects of ASD, and / or the risk factors of ASD, and / or the likelihood of developing ASD. In the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject having one or more signs, symptoms, or risk factors of social anxiety, including, but not limited to, consistent fear of situations in which you may be judged negatively, worry about embarrassing or humiliating yourself, intense fear of interacting or talking with strangers, fear that others will notice that you look anxious, fear of physical symptoms that may cause you embarrassment, such as blushing, sweating, trembling or having a shaky voice, avoidance of doing things or speaking to people out of fear of embarrassment avoidance of situations where you might be the center of attention, anxiety in anticipation of a feared activity or event, intense fear or anxiety during social situations, analysis of your performance and identification of flaws in your interactions aftera social situation, and expectation of the worst possible consequences from a negative experience during a social situation. In the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject who is diagnosed with social anxiety using diagnostic criteria, such as those found in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In some embodiments, a therapeutically effective amount reduces social anxiety, improves sociability, improves social novelty preference, or some combination thereof. In some embodiments, a therapeutically effective amount is achieved by multiple administrations. In some embodiments, a therapeutically effective amount is achieved with a single administration.

[0043] In some embodiments, in the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject having one or more signs, symptoms, or risk factors of a tauopathy, including, but not limited to disinhibition, apathy, loss of empathy, stereotypic behaviors, hyperorality, memory loss, difficulty communicating and reasoning, confusion, loss of coordination, depression, anxiety, paranoia, agitation, hallucinations, postural instability, vertical supranuclear ophthalmoplegia, asymmetrical limb apraxia, cortical function deficits, asymmetric onset of tremor, bradykinesia, rigidity, cerebellar ataxia, difficulty speaking, anomia, impaired comprehension, phonemic paraphasia, motor speech disorder, visuospatial disorientation, impaired executive abilities, or any combination thereof. For example, a “therapeutically effective amount” of the compositions of the present technology, includes levels at which the presence, frequency, or severity of one or more signs, symptoms, or risk factors of a tauopathy are, at a minimum, ameliorated. In some embodiments, a therapeutically effective amount reduces or ameliorates the physiological effects of a tauopathy, and / or the risk factors of a tauopathy, and / or the likelihood of developing a tauopathy. In some embodiments, a therapeutically effective amount is achieved by multiple administrations. In some embodiments, a therapeutically effective amount is achieved with a single administration.

[0044] In some embodiments, in the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject having one or more signs, symptoms, or risk factors of HD, including, but notlimited to, neuronal degeneration, uncontrolled movements, chorea, akinesia, bradykinesia, hypokinesia, dysarthria, dysphagia, dystonia, tremors, slurred speech, difficulty swallowing, eating, speaking or walking, weight loss, lung infections, insomnia, fatigue, seizures, cognitive decline, dementia, psychosis, hallucinations, delusions, violent outbursts, depression, anxiety, or any combination thereof. For example, a “therapeutically effective amount” of the compositions of the present technology, includes levels at which the presence, frequency, or severity of one or more signs, symptoms, or risk factors of HD are, at a minimum, ameliorated. In some embodiments, a therapeutically effective amount reduces or ameliorates the physiological effects of HD, and / or the risk factors of HD, and / or the likelihood of developing HD. In some embodiments, a therapeutically effective amount is achieved by multiple administrations. In some embodiments, a therapeutically effective amount is achieved with a single administration.

[0045] In some embodiments, in the methods described herein, compositions comprising the bacterial strain(s) of the present technology, or spores thereof, may be administered to a subject having one or more signs, symptoms, or risk factors of ALS, including, but not limited to muscle weakness, muscle wasting (atrophy), muscle fasciculations, muscle spasticity, slowness of movement, poor balance, incoordination, alterations in vocal quality, dysarthria, dysphagia, incomplete eye closure, drooling, pseudobulbar affect, premature death, increased brain translocator protein- 18 kDa (TSPO) expression, respiratory muscle weakness, dyspnea with mild exertion, supine dyspnea, and / or respiratory insufficiency. For example, a “therapeutically effective amount” of the compositions of the present technology, includes levels at which the presence, frequency, or severity of one or more signs, symptoms, or risk factors of ALS are, at a minimum, ameliorated. In some embodiments, a therapeutically effective amount reduces or ameliorates the physiological effects of ALS, and / or the risk factors of ALS, and / or the likelihood of developing ALS. In some embodiments, a therapeutically effective amount increases the time between symptomatic episodes and decreases the severity of symptoms during an episode. In some embodiments, a therapeutically effective amount is achieved by multiple administrations. In some embodiments, a therapeutically effective amount is achieved with a single administration.

[0046] As used herein, the terms “freeze-dried” or “freeze-drying” and “lyophilized” or “lyophilization” are used interchangeably and refer to a process that removes water from a product after it is frozen and placed under a vacuum and the products produced therefrom.

[0047] As used herein, “pharmaceutically acceptable carrier and / or diluent” or “pharmaceutically acceptable excipient” includes but is not limited to solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. In some embodiments, the pharmaceutically acceptable carrier comprises a polysaccharide, locust bean gum, an anionic polysaccharide, a starch, a protein, sodium ascorbate, glutathione, trehalose, sucrose, or pectin. In some embodiments, the polysaccharide comprises a plant, animal, algal, or microbial polysaccharide. In some embodiments, the polysaccharide comprises guar gum, inulin, amylose, chitosan, chondroitin sulphate, an alginate, or dextran. In some embodiments, the starch comprises rice starch. The use of such media and agents for biologically active substances is well known in the art. Further details of excipients are provided below. Supplementary active ingredients, such as antimicrobials, for example antifungal agents, can also be incorporated into the compositions.

[0048] As used herein, “pharmaceutically acceptable excipient” refers to substances and compositions that do not produce an adverse, allergic, or other untoward reaction when administered to an animal or a human. As used herein, the term includes all inert, nontoxic, liquid or solid fillers, or diluents that do not react with the therapeutic substance of the present technology in an inappropriate negative manner, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, preservatives and the like, for example liquid pharmaceutical carriers e.g., sterile water, saline, sugar solutions, Tris buffer, ethanol and / or certain oils.

[0049] As used herein, “probiotic” refers to bacteria comprising a component of the transient or endogenous flora of a subject administered to confer a beneficial prophylactic and / or therapeutic effect on the subject. Probiotics are generally known to be safe by those skilled in the art.

[0050] As used herein, “live biotherapeutic product(s)” refers to live microorganisms that are applicable to the prevention, treatment, or cure of a disease, condition, or disorder. Live biotherapeutic products can further comprise co-therapeutics, pharmaceutically acceptable excipients, or other useful compounds.

[0051] As used herein, “prevention,” “prevent,” or “preventing” of a disorder or condition refers to, in a statistical sample, reduction in the occurrence or recurrence of the disorder or condition in treated subjects / samples relative to an untreated controls, or refers delays the onset of one or more symptoms of the disorder or condition relative to the untreated controls.

[0052] As used herein “social anxiety” refers to an intense, persistent fear of social interactions. In some embodiments, a subject with social anxiety is diagnosed with social anxiety disorder. In some embodiments, a subject with social anxiety exhibits diminished social behavior.

[0053] As used herein “subject” and “patient” are used interchangeably. In some embodiments, the subject is an animal subject. In some embodiments, the animal subject is a mammal. In some embodiments, the mammalian subject is a human.

[0054] As used herein, the term “simultaneous” administration refers to the administration of at least two agents by the same route and at the same time or at substantially the same time.

[0055] As used herein, the term “separate” administration refers to an administration of at least two agents at the same time or at substantially the same time by different routes.

[0056] As used herein, the term “sequential” administration refers to administration of at least two agents at different times, the administration route being identical or different. More particularly, sequential use refers to the whole administration of one agent before administration of the other agent(s) commences. It is thus possible to administer one of the agents over several minutes, hours, or days before administering another.

[0057] A “synergistic therapeutic effect” refers to a greater-than-additive therapeutic effect which is produced by a combination of at least two therapeutic agents, and which exceeds that which would otherwise result from the individual administration of the agents.

[0058] For example, use of the bacterial strain(s) of the present technology in conjunction with other agents for the treatment of MS may result in a greater than additive therapeutic effect. In some embodiments, the synergistic effect may permit the use of lower doses of the bacterial strain(s) of the present technology and / or other agents than would be required if each were used alone.

[0059] As another example, use of a bacterial strain of the present technology in conjunction with other agents for the treatment of ASD and / or social anxiety, and / or cooccurring symptoms of either condition, may result in a greater than additive therapeutic effect. In some embodiments, the synergistic effect may permit the use of lower doses of the bacterial strain of the present technology and / or other agents than would be required if each were used alone.

[0060] As another example, use of bacterial strain(s) of the present technology in conjunction with other agents for the treatment of a tauopathy may result in a greater than additive therapeutic effect. In some embodiments, the synergistic effect may permit the use of lower doses of bacterial strain(s) of the present technology and / or other agents than would be required if each were used alone.

[0061] As another example, use of bacterial strain(s) of the present technology in conjunction with other agents for the treatment of Huntington’s Disease may result in a greater than additive therapeutic effect. In some embodiments, the synergistic effect may permit the use of lower doses of bacterial strain(s) of the present technology and / or other agents than would be required if each were used alone.

[0062] As another example, use of bacterial strain(s) of the present technology in conjunction with other agents for the treatment of ALS may result in a greater than additive therapeutic effect. In some embodiments, the synergistic effect may permit the use of lower doses of bacterial strain(s) of the present technology and / or other agents than would be required if each were used alone.

[0063] “Treating,” “treat,” “treated,” or “treatment” of a disease or disorder includes: (i) inhibiting the disease or disorder, z.e., arresting its development; (ii) relieving the disease or disorder, z.e., causing its regression; (iii) slowing progression of the disorder; and / or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the disease or disorder. In some embodiments, treating a disease or disorder comprises ameliorating the disease or disorder or a symptom of the disease or disorder.

[0064] It is to be appreciated that the various modes of treatment or prevention of medical diseases and conditions as described are intended to mean “substantial,” which includes total but also less than total treatment or prevention, and wherein some biologically or medically relevant result is achieved.II. Multiple Sclerosis

[0065] Multiple sclerosis (MS) is a nervous system disease of the brain and spinal cord that damages the myelin sheath coating on neurons. This damage results in impaired neuronal signaling with numerous downstream impacts including muscle weakness, loss of coordination and balance, painful or numbing sensations, and cognitive impairment. The condition affects approximately one million people in the United States alone, and is considered the most common demyelinating disease. MS includes four subtypes classified as clinically isolated syndrome, relapsing remitting MS, primary progressive MS, and secondary progressive MS. The exact cause of MS is not fully understood, rendering diagnosis challenging. Diagnostic tools include blood tests, spinal taps, MRIs of the central nervous system, evoked potential tests that measure neural signaling, and symptom pattern analysis. Symptoms and risk factors for MS include fatigue, dysesthesia, difficulty walking, numbness, tingling, spasticity, weakness, vision problems, vertigo, dizziness, bladder problems, bowel problems, sexual problems, pain and itching, cognitive function changes, emotional changes, depression, elevated levels of antibodies against myelin basic protein (MBP), myelin oligodendrocytic glycoprotein (MOG), Epstein Barr virus, ganglioside and / or neurofilaments, inflammation of the immune system, demyelination of neurons, impaired electrophysiology, elevated kappa free light chain abundance in cerebrospinal fluids, and / or lesions on the brain or spinal cord.

[0066] There is no cure for MS and there are limited treatment options currently available. The therapeutics that do exist are classified as disease modifying agents because they can modify, but not completely halt, the progression of MS. Disease modifying agents typically act via either immunomodulation or immunosuppression. Disease modifying agents currently approved in the United States to treat MS include injectable medications (Avonex® (interferon beta-la), Betaseron® (interferon beta-lb), Copaxone® (glatiramer acetate), Extavia® (interferon beta-lb), Glatiramer Acetate Injection (glatiramer acetate - generic equivalent of Copaxone), Glatopa® (glatiramer acetate - generic equivalent of Copaxone 20mg and 40mg doses), Kesimpta® (ofatumumab), Plegridy® (peginterferon beta- la), Rebif® (interferon beta- la)), oral medications (Aubagio® (teriflunomide), Bafiertam™ (monomethyl fumarate), Dimethyl Fumarate (dimethyl fumarate - generic equivalent of Tecfidera), Gilenya® (fmgolimod), Mavenclad® (cladribine), Mayzent® (siponimod), Ponvory™ (ponesimod), Tecfidera® (dimethyl fumarate), Vumerity® (diroximel fumarate), Zeposia® (ozanimod)), and infused medications (Briumvi™ (ublituximab-xiiy), Lemtrada® (alemtuzumab), Novantrone® (mitoxantrone), Ocrevus® (ocrelizumab), Tysabri® (natalizumab)). Additional emergency interventions to treat an MS attack and mitigate symptoms temporarily include corticosteroids and plasma exchanges.

[0067] Multiple animal models have been developed to study MS progression and test potential therapeutics. One such model is the myelin oligodendrocyte glycoprotein (MOG)- induced experimental allergic encephalomyelitis (EAE) method, which is well known to those in the art. Miyamura et. al., (2019). Myelin Oligodendrocyte Glycoprotein 35-55 (MOG 35-55)-induced Experimental Autoimmune Encephalomyelitis: A Model of Chronic Multiple Sclerosis, Bio-protocol 9 (24): e3453. EAE is a central nervous system autoimmune demyelinating disease that mimics many of the clinical and pathologic features of MS. The MOG murine model consists of a sensitization period, induced by a single subcutaneous injection of MOG emulsified in Complete Freund’s adjuvant, followed by intraperitoneal supplemental immune-stimulation with pertussis toxin carried out once at the day of EAE induction and once again 48 hours later. The resulting mouse model exhibits many of the signs and symptoms of MS and is responsive to known MS treatments. Two common methods to study MS treatments in the MOG model are disease severity scoringand electrophysiology experiments. Disease severity scoring uses a number of physical signs and symptoms of MS progression to create a disease severity score which can be tracked over time to determine whether a treatment intervention is having a positive impact. For an example of disease severity scoring in the study of MS, see Weaver, A. et al., An elevated matrix metalloproteinase (MMP) in an animal model of multiple sclerosis is protective by affecting Thl / Th2 polarization. The FASEB Journal, 19, 1668-1670 (2005). Electrophysiology can be assayed by methods well known in the art, involving the measurement of motor or sensory evoked potentials and determining whether various parameters, such as duration or sub-peak number, are improved by a treatment intervention. For an example of electrophysiology experimental design in the MOG mouse model, see Teixeira, N.B., Picolo, G., Giardini, A.C. et al. Alterations of peripheral nerve excitability in an experimental autoimmune encephalomyelitis mouse model for multiple sclerosis. J Neuroinflammation 17, 266 (2020).III. Autism Spectrum Disorder

[0068] Autism spectrum disorder (ASD) is the most commonly diagnosed neurodevelopmental disorder, with current estimates of more than 1% of affected children across nations. The condition affects approximately 1 in 45 children in the United States alone. Autism Spectrum Disorder includes three separably diagnosable conditions: autistic disorder, pervasive developmental disorder not otherwise specified, and Asperger syndrome. The patients form a highly heterogeneous group with only the behavioral phenotype in common. A few genetic markers for risk of ASD have been identified, but the vast majority of cases do not have a clear genetic linkage. Common symptoms, which are used to diagnose ASD via diagnostic systems such as questionnaires or surveys, include impaired social communication and interaction skills (e.g. a lack of eye contact, lack of responsiveness to name, lack of facial expressions, failure to interact with others, failure to make hand gestures, and / or failure to react to the emotions of other), restricted or repetitive behaviors or interests, delayed development of language skills, delayed development of movement skills, delayed development of cognitive or learning skills, hyperactive, impulsive, or inattentive behavior, epilepsy, seizures, gastrointestinal diseases or disorders, anxiety, excessive fear or fearlessness, or any combination thereof. Common diagnostic systems for ASD include Childhood Autism Rating Scale (CARS), Childhood AutismRating Scale 2 - Standard Form (CARS2-ST), Childhood Autism Rating Scale 2 - High Functioning (CARS2-ST), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Vineland Adaptive Behavior Scale II (VABS-II), Autism Diagnosis Interview (ADI-R), Autism Diagnostic Observation Schedule - Generic (ADOS-G), Gilliam Autism Rating Scale - Second Edition (GARS-2), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

[0069] There is no cure for ASD and treatment options are limited. One class of treatment includes courses of therapy. A course of therapy can provide various benefits to a subject suffering from ASD, including helping the subject control the behavioral symptoms associated with ASD. Courses of therapy used to treat subjects with ASD include talk therapy, discrete trial training, pivotal response training, speech and language therapy, occupational therapy, sensory integration therapy, physical therapy, social-relational training, and / or cognitive-behavior therapy. A second class of treatment includes therapeutics that treat co-occurring symptoms of ASD. Such co-occurring symptoms include, but are not limited to, irritability, high energy levels, inability to focus, self-harm, anxiety, depression, seizures, sleep problems, gastrointestinal pathologies, or any combination thereof. Therapeutics currently approved to treat co-occurring symptoms of ASD include risperidone and aripiprazole. There are no therapies currently approved to treat the core symptoms of ASD.

[0070] Animal models have been developed to study ASD and test novel therapeutics. One such widely accepted model is the BTBR mouse (BTBR T+Itpr3tf / J). Meyza KZ, Blanchard DC. The BTBR mouse model of idiopathic autism - Current view on mechanisms. Neurosci Biobehav Rev. 2017 May;76(Pt A):99-l 10. BTBR mice possess similar neuroanatomical features to some subpopulations of subjects with ASD. BTBR mice also exhibit ASD-like behaviors, including social impairments and repetitive behavior. BTBR mice therefore provide a useful background for testing the efficacy of new therapeutics that treat ASD.

[0071] A common experimental design to test behavioral phenotypes in mice involves the use of a 3 -chamber box, wherein the mice are placed in a central compartment and allowed to explore the chambers, and any stimulus objects therein, under different conditions. YangM, Silverman JL, Crawley JN. Automated three-chambered social approach task for mice. Curr Protoc Neurosci. 2011 Jul; Chapter 8: Unit 8.26. The box can be set up to test sociability, by allowing mice to explore other mice or inanimate objects, or to test social novelty preferences, by allowing mice to explore novel or familiar mice. Using the 3- chamber box test, various treatments can be applied to BTBR mice to determine whether the treatments can improve the ASD-like behavioral symptoms observed in BTBR mice.IV. Social Anxiety

[0072] Social anxiety is a common mental health disorder, wherein subjects experience varying levels of consistent, enhanced anxiety relating to social interactions. In extreme cases, such as clinically diagnosed social anxiety disorder, subjects can experience nausea and panic attacks. Common signs and symptoms of social anxiety including consistent fear of situations in which you may be judged negatively, worry about embarrassing or humiliating yourself, intense fear of interacting or talking with strangers, fear that others will notice that you look anxious, fear of physical symptoms that may cause you embarrassment, such as blushing, sweating, trembling or having a shaky voice, avoidance of doing things or speaking to people out of fear of embarrassment avoidance of situations where you might be the center of attention, anxiety in anticipation of a feared activity or event, intense fear or anxiety during social situations, analysis of your performance and identification of flaws in your interactions after a social situation, and expectation of the worst possible consequences from a negative experience during a social situation. Social anxiety disorder can be diagnosed using diagnostic systems, including the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), based on physical exams, symptom severity and frequency, anxiety triggers, and questionnaires about social anxiety symptoms. Common therapies for social anxiety include psychotherapy, cognitive behavioral therapy, selective serotonin reuptake inhibitors (such as paroxetine or sertraline), serotonin and norepinephrine reuptake inhibitors (such as venlafaxine), anti-depressants, anti-anxiety medications, benzodiazepines, and beta blockers.

[0073] Multiple animal models have been developed that exhibit signs and symptoms of social anxiety, including the BTBR mouse described above. BTBR mice have been characterized as exhibiting social anxiety like behaviors that were reversible to normalsocialization with the administration of an anti-anxiety medication. Pobbe RL el al., General and social anxiety in the BTBR T+ tf / J mouse strain. Behav Brain Res. 2011 Jan 1 ;216(l):446-51. The 3-chamber test, as described above, is commonly used to test social anxiety in mouse models by observing social behavioral patterns.V. Tauopathies

[0074] Tauopathies is an umbrella term encompassing a number of neurodegenerative disorders that are characterized by Tau deposits in the brain and central nervous systems. In certain Tauopathies the Tau deposits also contain other proteins at various abundances, such as beta-amyloid. Mutations to the microtubule associated protein Tau (MAPT) gene that encodes Tau can lead to the pathogenic isoforms 3R and 4R and deposits that are made up of 3R, 4R, or a mix therein. At least the following mutations are known to be pathogenic: R5H, R5L, G55R, A152T, K257T, I260V, L266V, G272V, G273R, N279K, K280del, L284L, L284R, S285R, C291R, N296del, N296D, N296H, N296N, P301L, P301S, P301T, G303V, S305I, S305N, S305S, L315L, L315R, K317M, K317N, S320F, S320Y, P332S, G335A, G335S, G335V, Q336H, Q336R, V337M, E342V, S352L, S356T, V363I, P364S, G366R, K369I, E372G, G389R, P397S, R406W, R406G, and N410H. Tau deposits can occur in multiple locations, including neurons, glial cells, and extracellular space.Tauopathies are further characterized by symptoms including, but not limited to: disinhibition, apathy, loss of empathy, stereotypic behaviors, hyperorality, memory loss, difficulty communicating and reasoning, confusion, loss of coordination, depression, anxiety, paranoia, agitation, hallucinations, postural instability, vertical supranuclear ophthalmoplegia, asymmetrical limb apraxia, cortical function deficits, asymmetric onset of tremor, bradykinesia, rigidity, cerebellar ataxia, difficulty speaking, anomia, impaired comprehension, phonemic paraphasia, motor speech disorder, visuospatial disorientation, impaired executive abilities, or any combination thereof. At a cellular level, signs of tauopathies include tau deposits, elevated reactive oxygen species levels, and neuronal degradation.

[0075] To date, 26 different tauopathies have been identified. Known tauopathies include, but are not limited to: Alzheimer's disease, amyotrophic lateral sclerosis, Parkinsonismdementia complex, anti -IgLON5 -related tauopathy, Caribbean Parkinsonism, chronictraumatic encephalopathy, diffuse neurofibrillary tangles with calcification, progressive supranuclear palsy, Down syndrome, Familial British dementia, Familial Danish dementia, Niemann-Pick disease type C, non-Guamanian motor neuron disease with neurofibrillary tangles, postencephalitic Parkinsonism, primary age-related tauopathy, progressive ataxia, palatal tremor, neurofibrillary dementia, familial frontotemporal dementia, Parkinsonism, Pick's disease, argyrophilic grain disease, corticobasal degeneration, Guadeloupean Parkinsonism, globular glial tauopathy, Huntington's Disease, SLC9a-related Parkinsonism, Tau astrogliopathy, and aging-related Tau astrogliopathy. Despite the prevalence of tauopathies, most still lack effective treatment options. For example, dementia afflicts more than 55 million people worldwide, but there are limited treatment options available and no cure.

[0076] While many pathogenic mutations that cause Tau aggregation have been identified, the mechanism of pathogenesis is still uncertain, as is the degree to which Tau aggregation impacts pathogenesis. Therapeutics that are being developed for tauopathies include, but are not limited to: anti-Tau antibodies, vaccines inducing immunity against tau, tau-disaggregation agents, anti-tau-expression agents, anti-amyloid plaque agents, antiamyloid antibodies, modulators of Tau phosphorylation, modulators of Tau acylation, histone deacetylase inhibitors, modulators of Tau glycosylation, inhibitors of Tau glycosylation, modulators of Tau truncation, proteasome stimulators, USP14 inhibitors, phosphodiesterase inhibitors, autophagy activators, chaperone modulators, co-chaperone modulators, and Tau oriented multi -target directed ligands.

[0077] Animal models have been developed to study tauopathies, including in zebrafish (Dariio rerio) via mutations to the zebrafish MAPT gene which result in a truncated tau protein. The zebrafish model exhibits many of the signs of tauopathies, including striatal nerve degeneration, diminished mobility, and elevated reactive oxygen levels in the brain. Therefore, the zebrafish model provides a useful background for testing the efficacy of new therapeutics that treat tauopathies.VI. Huntington’s Disease

[0078] Huntington’s Disease (HD) is a neurodegenerative, autosomal dominant genetic disease caused by a mutation to the huntingtin gene (HTT). HD is primarily prevalent in those of European descent, and estimates of disease prevalence range from 4 in 100,000 to 9 in 100,000. The HTT gene contains a variable number of CAG trinucleotide repeats encoding a polyglutamine tract. Less than 27 CAG repeats is classified as a normal level with no risk of disease. Between 27 and 35 repeats is considered an intermediate level with elevated risk of disease to an individual’s offspring, but no disease risk to the individual. Between 36 and 39 repeats is classified as reduced penetrance, with a risk of disease to the individual and to their offspring. Greater than 40 repeats is considered full penetrance, meaning the individual will have HD and any offspring will have a risk of the disease. The mutated HTT protein with an elongated polyglutamine tract is prone to cleavage and aggregation in neurons, forming inclusion bodies in the cytoplasm and nucleus that gradually interfere with neuronal activity and cause cell death. Initially the primary region affected is the dorsal striatum, however as HD progresses the entire brain begins to be affected. Striatal medium spiny neurons are the most prone to diminished activity and cell death during early disease stages.

[0079] As HD progresses, increasing neuronal interference and cell death cause the symptoms associated with HD, including, but not limited to: neuronal degeneration, uncontrolled movements, chorea, akinesia, bradykinesia, hypokinesia, dysarthria, dysphagia, dystonia, tremors, slurred speech, difficulty swallowing, eating, speaking or walking, weight loss, lung infections, insomnia, fatigue, seizures, cognitive decline, dementia, psychosis, hallucinations, delusions, violent outbursts, depression, or anxiety, or any combination thereof. At a cellular level, signs of HD include inclusion bodies and neuronal degradation, particularly in the dorsal striatum during early disease stages. There are no therapies that treat the underlying cause of HD, and limited options exist to treat the symptoms associated with the disease. In the United States only tetrabenazine and deutetrabenazine are approved for treating chorea, the involuntary jerking and writhing motions associated with HD. Other medications used to treat the symptoms associated with HD include olanzapine, pimozide, risperidone, fluphenazine, amantadine, levetiracetam, clonazepam, haloperidol, aripiprazole, quetiapine, citalopram, escitalopram, fluoxetine,sertraline, divalproex, carbamazepine, lamotrigine, antipsychotics, antidepressants, anticonvulsants, mood-stabilizing drugs, and anti-anxiety agents.

[0080] While the mutation that causes HD is known, the function of the HTT protein is still poorly characterized and the exact pathology of the disease is not entirely understood. Current therapies being developed for HD include, but are not limited to, methods for silencing the HTT gene, reversing the HTT mutation, increasing HTT clearance, increasing inclusion body clearance, improving neuronal survival (via correction of transcriptional regulation using histone deacetylase inhibitors, modulating aggregation of huntingtin, improving metabolism and mitochondrial function and restoring function of synapses), and replacing dead or damaged neurons via stem cell therapy.

[0081] Animal models have been developed to study HD, including in zebrafish (Danio rerio) via mutations to the zebrafish HTT gene. The zebrafish model exhibits many of the signs of HD, including striatal nerve degeneration, chorea, and diminished mobility. Therefore, the zebrafish model provides a useful background for testing the efficacy of new therapeutics that treat HD.VII. Amyotrophic Lateral Sclerosis (ALS)

[0082] Amyotrophic Lateral Sclerosis (ALS) is a fatal, progressive neuromuscular condition characterized by weakness, muscle wasting, fasciculations, and increased reflexes. ALS is characterized by adult-onset, idiopathic, progressive degeneration of anterior horn cells and upper and lower motor neurons resulting in progressive muscle weakness, wasting, and fasciculations. Atrophy of the anterior horn cells and replacement of the large motor neurons by fibrous astrocytes (gliosis) causes the affected anterior and lateral columns of the spinal cord to become hard, hence the term “lateral sclerosis.” Typical signs and symptoms of ALS include, but are not limited to, muscle weakness, muscle wasting (atrophy), muscle fasciculations, muscle spasticity, slowness of movement, poor balance, incoordination, alterations in vocal quality, dysarthria, dysphagia, incomplete eye closure, drooling, pseudobulbar affect, premature death, increased brain translocator protein- 18 kDa (TSPO) expression, respiratory muscle weakness, dyspnea with mild exertion, supine dyspnea, respiratory insufficiency, and / or elevated plasma or CSF levels ofneurofilament light chain (NfL). Respiratory insufficiency (RI) in ALS usually emerges in the late stage of disease progression, although it may sometimes be the presenting feature. Respiratory complications, especially hypoventilation, reduced bronchial clearance, and lung infection account for the majority of deaths in ALS. Mild respiratory involvement causes fatigue in daily-life activities and disruption of sleep, with negative impact on quality of life, and hypoxemia may impair cognitive function. Biomarkers of ALS, such a neurofilament light chain (NfL), can be valuable for defining subgroups of patients and to track disease progression and treatment response. Neurofilament light chains are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. CSF, serum, and plasma NfL levels have been shown to discriminate patients with ALS from healthy controls with high sensitivity and specificity, and correlate with disease progression or survival in patients with ALS (Lu et al., Neurology, 84(22):2247-2257 (Jun. 2015)).

[0083] Up to 10% of ALS is familial. Several causative genes are known, including mutant superoxide dismutase 1 (SOD1 mutant C9orf72 (i.e., a G4C2 hexanucleotide repeat in the C9orf72 gene), mutant FUS (fused in sarcoma), mutant TARDBP gene leading to modifications of the TAR-DNA binding protein 43 (TDP-43), and optineurin.

[0084] The clinical presentation varies, depending on the area of the nervous system that is damaged and progression of the pathologic changes. The classic presentation of ALS is insidious, progressive, asymmetric muscular weakness and atrophy along with neurologic signs, particularly fasciculations and hyperreflexia. It usually presents with problems in dexterity or gait resulting from muscle weakness. Difficulty in speaking or swallowing is the initial symptom in the bulbar form of the disease. Over a period of months or years, patients with ALS develop severe, progressive muscular weakness and other symptoms caused by loss of function in both upper and lower motor neurons. Sphincter control, sensory function, intellectual abilities and skin integrity are preserved. Patients become completely disabled, often requiring ventilatory support and gastrostomy. Death usually occurs within five years of diagnosis and is typically attributed to respiratory failure or cachexia. The diagnosis of ALS is clinical, based on the characteristic signs of progressive weakness, atrophy, fasciculations and hyperreflexia affecting several regions of the body. The early differential diagnosis may include musculoskeletal, neurologic, or systemicconditions. The etiology of the disease is unknown. Current management involves aggressive, individualized alleviation of symptoms and complications.

[0085] There is no cure for ALS and there are limited treatment options currently available. The agents currently labeled for the treatment of ALS are riluzole (Rilutek®, Tiglutik™, Exservan™), tofersen (QALSODY™), sodium phenylbutyrate and taurursodiol (RELYVRIO™), dextromethorphan / quinidine (Nuedexta®), and edaravone (Radicava®). At least one other drug (mecasermin) is under consideration by the U.S. Food and Drug Administration. Various symptomatic treatments including baclofen (Lioresal®), diazepam (Valium®), dantrolene (Dantrium®), nonsteroidal anti-inflammatory agents, anticonvulsive medications, such as carbamazepine (Tegretol) or phenytoin (Dilantin®), amitriptyline (Elavil®), nortriptyline (Pamelor™), or Lorazepam (Ativan®), may be helpful.

[0086] Multiple animal models have been developed to study ALS and test potential therapeutics. The study of animal models is essential to understand the pathological mechanisms of ALS and to develop new treatments for it, given its heterogeneity, complexity, and unclear etiology. Several models have been described, based on genetic manipulation of 801)1, TARDBP, FUS, and C9ORF72, as well as other genes and chemical exposures in different species: C. elegans, fruit flies, zebrafish, mice, rats and non-human primates. Zebrafish (Danio rerio) is a small tropical fish from southeast Asia, that was initially used as a model organism for developmental studies, and it has been established as a prominent disease model for drug screening and preclinical trials. Zebrafish are vertebrates and have a high degree of conservation of genes and processes implicated in human ALS. Additionally, zebrafish embryos develop ex vivo and are optically transparent, which facilitates microscopy techniques and makes in vivo imaging of motor neurons and ALS-relevant pathology possible.VIII. ART 12 and ART24

[0087] The technology of the present disclosure relates to the use of the ART12 and / or ART24 strain, or spores thereof, to treat or prevent MS, ASD and / or social anxiety, a tauopathy, HD, and ALS. ART12 or ADS012 refers to a bacterial strain, or spore thereof, having been deposited under NCIMB Accession No. 43087, or compositions comprising thestrain. ART24 or ADS024 refers to a bacterial strain, or spore thereof, having been deposited under NCIMB Accession No. 43088, or compositions comprising the strain.

[0088] In some embodiments, bacterial strains of the present technology, or spores thereof, are used in methods and compositions for treating or preventing MS, ASD and / or social anxiety, a tauopathy, HD, and ALS. In some embodiments, the bacterial strains comprise a probiotic for preventing or controlling MS, ASD and / or social anxiety, a tauopathy, HD, and ALS. In some embodiments, the bacterial strains comprise a live biotherapeutic product for preventing or controlling MS, ASD and / or social anxiety, a tauopathy, HD, and ALS. In some embodiments, compositions of the present technology comprise vegetative bacterial cells. In some embodiments, compositions of the present technology comprise bacterial spores. In some embodiments, compositions of the present technology comprise a combination of vegetative bacterial cells and bacterial spores. In some embodiments, the compositions of the present technology comprise ART12. In some embodiments, the compositions of the present technology comprise ART24. In some embodiments, the compositions of the present technology comprise ART12 and ART24. In some embodiments, the compositions of the present technology comprise an ART12 and / or ART24 bacterial strain that has been physically destructed or lysed. In some embodiments, the compositions of the present technology comprise an isolated fraction of lysed ART12 and / or ART24 bacteria.

[0089] In some embodiments, the bacterial strain(s) of the present technology, or spores thereof, are used in methods and edible product compositions for treating or preventing MS, ASD and / or social anxiety, a tauopathy, HD, and ALS in a subject in need thereof. In some embodiments, the bacterial strain(s) comprises a dietary supplement for preventing or controlling MS, ASD and / or social anxiety, a tauopathy, HD, and ALS in a subject in need thereof.IX. Therapeutic and Prophylactic Methods

[0090] The following discussion is presented by way of example only, and is not intended to be limiting.

[0091] One aspect of the present technology includes methods of treating or preventing MS, ASD and / or social anxiety, a tauopathy, HD, and ALS in a subject diagnosed as having, suspected as having, or at risk of having MS, ASD and / or social anxiety, a tauopathy, HD, or ALS. In therapeutic applications, compositions or medicaments comprising the ART12 and / or ART24 bacterial strain, or spore thereof, are administered to a subject suspected of, or already suffering from MS, ASD and / or social anxiety, a tauopathy, HD, or ALS (such as, e.g., subjects exhibiting one or more signs or symptoms of MS, ASD and / or social anxiety, a tauopathy, HD, or ALS), in an amount sufficient to cure, or at least partially arrest, the signs or symptoms of the MS, ASD and / or social anxiety, a tauopathy, HD, or ALS, including its complications and intermediate pathological phenotypes in development of the disease.

[0092] Subjects suffering from MS can be identified by any or a combination of diagnostic or prognostic assays known in the art. For example, typical symptoms of MS include, but are not limited to: fatigue, dysesthesia, difficulty walking, numbness, tingling, spasticity, weakness, vision problems, vertigo, dizziness, bladder problems, bowel problems, sexual problems, pain and itching, cognitive function changes, emotional changes, depression, elevated levels of antibodies against myelin basic protein (MBP), myelin oligodendrocytic glycoprotein (MOG), Epstein Barr virus, ganglioside and / or neurofilaments, inflammation of the immune system, demyelination of neurons, impaired electrophysiology, elevated kappa free light chain abundance in cerebrospinal fluids, and / or lesions on the brain or spinal cord. In some embodiments MS is diagnosed using imaging technology to examine the brain and spinal column for abnormalities.

[0093] In some embodiments, subjects with MS treated with the bacterial strain(s) of the present technology, or spores thereof, will show amelioration or elimination of one or more of the following symptoms: fatigue, dysesthesia, difficulty walking, numbness, tingling, spasticity, weakness, vision problems, vertigo, dizziness, bladder problems, bowel problems, sexual problems, pain and itching, cognitive function changes, emotional changes, depression, elevated levels of antibodies against myelin basic protein (MBP), myelin oligodendrocytic glycoprotein (MOG), ganglioside, Epstein Barr virus, and / or neurofilaments, inflammation of the immune system, demyelination of neurons, impairedelectrophysiology, elevated kappa free light chain abundance in cerebrospinal fluids, and / or lesions on the brain or spinal cord.

[0094] In one aspect, the present technology provides a method for preventing or delaying the onset of MS or symptoms of MS in a subject at risk of having MS. In some embodiments, the bacterial strain(s) of the present technology is formulated as a probiotic useful as a food supplement and for re-establishing beneficial bacteria in the intestinal tract. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic product useful in pharmaceutical applications. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic edible product useful in pharmaceutical applications.

[0095] Subjects suffering from ASD can be identified by any or a combination of diagnostic or prognostic assays known in the art. For example, typical symptoms of ASD include, but are not limited to: impaired social communication and interaction skills (e.g. a lack of eye contact, lack of responsiveness to name, lack of facial expressions, failure to interact with others, failure to make hand gestures, and / or failure to react to the emotions of other), restricted or repetitive behaviors or interests, delayed development of language skills, delayed development of movement skills, delayed development of cognitive or learning skills, hyperactive, impulsive, or inattentive behavior, epilepsy, seizures, gastrointestinal diseases or disorders, anxiety, excessive fear or fearlessness, or any combination thereof. In some cases a subject suffering from ASD can be identified using a diagnostic system. For example, diagnostic systems for ASD include, but are not limited to, the Childhood Autism Rating Scale (CARS), the Childhood Autism Rating Scale 2 - Standard Form (CARS2-ST), the Childhood Autism Rating Scale 2 - High Functioning (CARS2-ST), the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS), the Vineland Adaptive Behavior Scale II (VABS-II), the Autism Diagnosis Interview (ADI-R), the Autism Diagnostic Observation Schedule - Generic (ADOS-G), the Gilliam Autism Rating Scale - Second Edition (GARS-2), and / or the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

[0096] In some embodiments, subjects with ASD treated with the bacterial strain of the present technology, or spores thereof, will show amelioration or elimination of one or moreof the following symptoms: impaired social communication and interaction skills (e.g. a lack of eye contact, lack of responsiveness to name, lack of facial expressions, failure to interact with others, failure to make hand gestures, and / or failure to react to the emotions of other), restricted or repetitive behaviors or interests, delayed development of language skills, delayed development of movement skills, delayed development of cognitive or learning skills, hyperactive, impulsive, or inattentive behavior, epilepsy, seizures, gastrointestinal diseases or disorders, anxiety, and excessive fear or fearlessness.

[0097] In one aspect, the present technology provides a method for preventing or delaying the onset of ASD or symptoms of ASD in a subject at risk of having ASD. In some embodiments, the bacterial strain(s) of the present technology is formulated as a probiotic useful as a food supplement and for re-establishing beneficial bacteria in the intestinal tract. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic edible product useful in pharmaceutical applications.

[0098] Subjects suffering from social anxiety can be identified by any or a combination of diagnostic or prognostic assays known in the art. For example, typical symptoms of social anxiety include, but are not limited to: consistent fear of situations in which you may be judged negatively, worry about embarrassing or humiliating yourself, intense fear of interacting or talking with strangers, fear that others will notice that you look anxious, fear of physical symptoms that may cause you embarrassment, such as blushing, sweating, trembling or having a shaky voice, avoidance of doing things or speaking to people out of fear of embarrassment avoidance of situations where you might be the center of attention, anxiety in anticipation of a feared activity or event, intense fear or anxiety during social situations, analysis of your performance and identification of flaws in your interactions after a social situation, and expectation of the worst possible consequences from a negative experience during a social situation. In some cases a subject suffering from social anxiety is diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

[0099] In some embodiments, subjects with social anxiety treated with the bacterial strain(s) of the present technology, or spores thereof, will show amelioration or elimination of one or more of the following symptoms: consistent fear of situations in which you may be judged negatively, worry about embarrassing or humiliating yourself, intense fear ofinteracting or talking with strangers, fear that others will notice that you look anxious, fear of physical symptoms that may cause you embarrassment, such as blushing, sweating, trembling or having a shaky voice, avoidance of doing things or speaking to people out of fear of embarrassment avoidance of situations where you might be the center of attention, anxiety in anticipation of a feared activity or event, intense fear or anxiety during social situations, analysis of your performance and identification of flaws in your interactions after a social situation, and expectation of the worst possible consequences from a negative experience during a social situation.

[0100] In one aspect, the present technology provides a method for preventing or delaying the onset of social anxiety or symptoms of social anxiety in a subject at risk of having social anxiety. In some embodiments, the bacterial strain of the present technology is formulated as a probiotic useful as a food supplement and for re-establishing beneficial bacteria in the intestinal tract. In some embodiments, the bacterial strain of the present technology is formulated as a live biotherapeutic product useful in pharmaceutical applications. In some embodiments, the bacterial strain of the present technology is formulated as a live biotherapeutic edible product useful in pharmaceutical applications.

[0101] Subjects suffering from a tauopathy can be identified by any or a combination of diagnostic or prognostic assays known in the art. For example, typical symptoms of tauopathies include, but are not limited to: tau deposits, disinhibition, apathy, loss of empathy, stereotypic behaviors, hyperorality, memory loss, difficulty communicating and reasoning, confusion, loss of coordination, depression, anxiety, paranoia, agitation, hallucinations, postural instability, vertical supranuclear ophthalmoplegia, asymmetrical limb apraxia, cortical function deficits, asymmetric onset of tremor, bradykinesia, rigidity, cerebellar ataxia, difficulty speaking, anomia, impaired comprehension, phonemic paraphasia, motor speech disorder, visuospatial disorientation, impaired executive abilities, or any combination thereof. In some embodiments the tauopathy is diagnosed using imaging technology to examine the brain and spinal column for abnormalities. In some embodiments, the tauopathy is diagnosed using genetic testing.

[0102] In some embodiments, subjects with tauopathies treated with the bacterial strain(s) of the present technology, or spores thereof, will show amelioration or elimination of one ormore of the following symptoms: tau aggregates, disinhibition, apathy, loss of empathy, stereotypic behaviors, hyperorality, memory loss, difficulty communicating and reasoning, confusion, loss of coordination, depression, anxiety, paranoia, agitation, hallucinations, postural instability, vertical supranuclear ophthalmoplegia, asymmetrical limb apraxia, cortical function deficits, asymmetric onset of tremor, bradykinesia, rigidity, cerebellar ataxia, difficulty speaking, anomia, impaired comprehension, phonemic paraphasia, motor speech disorder, visuospatial disorientation, impaired executive abilities, or any combination thereof.

[0103] In one aspect, the present technology provides a method for preventing or delaying the onset of a tauopathy or symptoms of a tauopathy in a subject at risk of having a tauopathy. In some embodiments, the bacterial strain(s) of the present technology is formulated as a probiotic useful as a food supplement and for re-establishing beneficial bacteria in the intestinal tract. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic product useful in pharmaceutical applications. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic edible product useful in pharmaceutical applications.

[0104] Subjects suffering from HD can be identified by any or a combination of diagnostic or prognostic assays known in the art. For example, typical symptoms of HD include, but are not limited to: neuronal degeneration, uncontrolled movements, chorea, akinesia, bradykinesia, hypokinesia, dysarthria, dysphagia, dystonia, tremors, slurred speech, difficulty swallowing, eating, speaking or walking, weight loss, lung infections, insomnia, fatigue, seizures, cognitive decline, dementia, psychosis, hallucinations, delusions, violent outbursts, depression, or anxiety, or any combination thereof. In some embodiments HD is diagnosed using imaging technology to examine the brain and spinal column for abnormalities. In some embodiments, HD is diagnosed using genetic testing. In some embodiments, HD is diagnosed using a family medical history.

[0105] In some embodiments, subjects with HD treated with the bacterial strain(s) of the present technology, or spores thereof, will show amelioration or elimination of one or more of the following symptoms: neuronal degeneration, uncontrolled movements, chorea, akinesia, bradykinesia, hypokinesia, dysarthria, dysphagia, dystonia, tremors, slurredspeech, difficulty swallowing, eating, speaking or walking, weight loss, lung infections, insomnia, fatigue, seizures, cognitive decline, dementia, psychosis, hallucinations, delusions, violent outbursts, depression, or anxiety, or any combination thereof.

[0106] In one aspect, the present technology provides a method for preventing or delaying the onset of a HD or symptoms of HD in a subject at risk of having HD. In some embodiments, the bacterial strain(s) of the present technology is formulated as a probiotic useful as a food supplement and for re-establishing beneficial bacteria in the intestinal tract. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic product useful in pharmaceutical applications. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic edible product useful in pharmaceutical applications.

[0107] Subjects suffering from ALS can be identified by any or a combination of diagnostic or prognostic assays known in the art. For example, typical symptoms of ALS include, but are not limited to: muscle weakness, muscle wasting (atrophy), muscle fasciculations, muscle spasticity, slowness of movement, poor balance, incoordination, alterations in vocal quality, dysarthria, dysphagia, incomplete eye closure, drooling, pseudobulbar affect, premature death, increased brain translocator protein-18 kDa (TSPO) expression, respiratory muscle weakness, dyspnea with mild exertion, supine dyspnea, respiratory insufficiency, and / or elevated plasma or CSF levels of neurofilament light chain (NfL).

[0108] In some embodiments, subjects with ALS treated with the bacterial strain(s) of the present technology, or spores thereof, will show amelioration or elimination of one or more of the following symptoms: muscle weakness, muscle wasting (atrophy), muscle fasciculations, muscle spasticity, slowness of movement, poor balance, incoordination, alterations in vocal quality, dysarthria, dysphagia, incomplete eye closure, drooling, pseudobulbar affect, premature death, increased brain translocator protein-18 kDa (TSPO) expression, respiratory muscle weakness, dyspnea with mild exertion, supine dyspnea, respiratory insufficiency, and / or elevated plasma or CSF levels of neurofilament light chain (NfL). In some embodiments, treatment with the bacterial strain(s) of the presenttechnology, or spores thereof, will prevent or delay the onset of plasma accumulation of neurofilament light chain (NfL).

[0109] In one aspect, the present technology provides a method for preventing or delaying the onset of ALS or symptoms of ALS in a subject at risk of having ALS. In some embodiments, the bacterial strain(s) of the present technology is formulated as a probiotic useful as a food supplement and for re-establishing beneficial bacteria in the intestinal tract. In some embodiments, the bacterial strain(s) of the present technology is formulated as a live biotherapeutic product useful in pharmaceutical applications.X. Modes of Administration and Effective Dosages

[0110] Compositions of the present technology for use in preventing, ameliorating, or treating MS, ASD and / or social anxiety, tauopathies, HD, or ALS, and / or reducing the severity of one or more risk factors, signs, or symptoms associated with MS, ASD and / or social anxiety, tauopathies, HD, and ALS, include live ART12 and / or ART24 bacteria according to the present technology, provided in the form of vegetative cells and / or spores. In some embodiments, the bacterial strain(s) is formulated as a live biotherapeutic product. In some embodiments, the bacterial strain(s) is formulated as a probiotic. In some embodiments, the bacterial strain(s) is lyophilized. The compositions of the present technology are administered to the subject in effective amounts (i.e., amounts that have desired therapeutic effect). The dose and dosage regimen will depend upon the type and degree of MS progression, ASD and / or social anxiety, identity of the tauopathy and / or the degree of tauopathy progression, nature of the HTT mutation associated with the case of HD, the degree of HD, the progression of HD, the degree of ALS progression, and symptom severity in the subject, the characteristics of the ART12 and / or ART24 strain used, e.g., its therapeutic index, the subject, and the subject’s history. The effective amount may be determined during pre-clinical trials and clinical trials by methods familiar to physicians and clinicians.

[0111] Compositions of the present technology may be formulated for adding to food, or used directly as a food supplement. The formulation may further include other agents or nutrients for promoting spore germination and / or bacterial growth. Compositions of thepresent technology may be formulated for rectal administration, which may be advantageous for subjects with MS, ASD and / or social anxiety, a tauopathy, HD who have difficulty swallowing.

[0112] Edible products of the present technology may be formulated for adding to food, or used directly as a dietary supplement. In some embodiments, the edible product comprises a fermented food product, soybean, mushroom, mung bean, locus bean, or rice. In some embodiments, the soybean is fermented soybean or fermented soybean paste. The formulation may further include other agents or nutrients for promoting spore germination and / or bacterial growth.

[0113] Additional components of the compositions of the present technology may include a preservative. In some embodiments, the preservative is selected from the group consisting of sucrose, sodium ascorbate, and glutathione. In some embodiments the preservative is a cryoprotectant selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide. In some embodiments, the cryoprotectant is selected from the group consisting of inosine-5’ -monophosphate (IMP), guanosine-5 ’-monophosphate (GMP), adenosine-5’ -monophosphate (AMP), uranosine-5’ -monophosphate (UMP), cytidine-5’- monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, skim milk, and cryoprotectant 18.

[0114] The ARTT2 and / or ART24 bacterial strains described herein can be incorporated into pharmaceutical compositions for administration, singly or in combination, and given to a subject for the treatment or prevention of a disorder described herein. Such compositions typically include the active agent and a pharmaceutically acceptable carrier. As used herein the term “pharmaceutically acceptable carrier” includes saline, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Supplementary active compounds can also be incorporated into the compositions. Carriers can be solid-based dry materials for formulations in powdered form, and can be liquid or gel-based materials for formulations in liquid or gel forms, which forms depend, in part, upon the routes or modesof administration. In some embodiments, the pharmaceutically acceptable carrier comprises a polysaccharide, locust bean gum, an anionic polysaccharide, a starch, a protein, sodium ascorbate, glutathione, trehalose, sucrose, or pectin. In some embodiments, the polysaccharide comprises a plant, animal, algal, or microbial polysaccharide. In some embodiments, the polysaccharide comprises guar gum, inulin, amylose, chitosan, chondroitin sulphate, an alginate, or dextran. In some embodiments, the starch comprises rice starch.

[0115] Pharmaceutical compositions are typically formulated to be compatible with its intended route of administration. Examples of routes of administration include enteric (e.g., oral, sublingual, buccal, or rectal) administration. A therapeutic composition can be formulated to be suitable for oral administration in a variety of ways, for example in a liquid, a powdered food supplement, a solid food, a packaged food, a wafer, tablets, troches, or capsules, e.g., gelatin capsules, and the like. In some embodiments, the therapeutic compositions of the present technology comprise lyophilized ART12 and / or ART24. In some embodiments, the lyophilized ART12 and / or ART24 is encapsulated. A therapeutic composition can be formulated to be suitable for rectal administration in a variety of ways, for example in a suppository, liquid enema, or foam. Other formulations will be readily apparent to one skilled in the art. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide.

[0116] Additionally or alternatively, for edible products, pharmaceutical compositions of the present technology may be formulated as dietary supplements, nutraceutical compositions, food additives, food compositions, food compositions in bulk, food additives in bulk, medical foods, or foods for special dietary use, for enteric (e.g., oral, sublingual) administration.

[0117] Dosage, toxicity and therapeutic efficacy of any therapeutic agent can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds may be within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route ofadministration utilized. For any compound used in the methods, the therapeutically effective dose can be estimated initially from cell culture assays. A dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 ( / .< ., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to determine useful doses in humans accurately.

[0118] In some embodiments, the “edible products” such as whole soybeans and / or soybean pastes, are inoculated with a concentration of ART12 and / or ART24 ranging from at least about 1 x 102colony forming units (CFU) / mL to at least about 1 x 1014CFU / mL, or any value in between. For example, in some embodiments, the edible products are inoculated with at least about 1 x 103CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 104CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 105CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 106CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 107CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 108CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 109CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x IO10CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 1011CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, at least about 1 x 1012CFU / mL to at least about 1 x 1014CFU / mL ART 12 and / or ART24, or at least about 1 x 1013CFU / mL to at least about 1 x 1014CFU / mLART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 6 x 108CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 6 x 109CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 104CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 105CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 106CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 107CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 108CFU / mL ART12 and / or ART24. In some embodiments, the edibleproducts are inoculated with at least about 1 x 109CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x IO10CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 1011CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 1012CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 1013CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 1014CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with a total cell count (TCC) of ART12 and / or ART24 that would correspond to the CFU / mL amounts described herein.

[0119] In some embodiments, the compositions of the present technology are formulated at about IxlO8colony forming units (CFU) per ml to about IxlO12CFU per ml of ART24 and / or ART12 bacterium i.e., vegetative cell) or bacterial spore. In some embodiments, the compositions of the present technology are formulated with at least about I x lO3CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium (i.e., vegetative cell) or bacterial spore, at least about 1 x 104CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about I x lO5CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about 1 x 106CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about 1 x 107CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about I x lO8CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about 1 x 109CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about 1 x IO10CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about I x lO11CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, at least about 1 x 1012CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore, or at least about 1 x 1013CFU / mL to at least about 1 x 1014CFU / mL ART12 and / or ART24 bacterium or bacterial spore. In some embodiments, the compositions comprise at least about 6 x 108CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 6 x 109CFU / mL ART12 and / or ART24. In someembodiments, the compositions at least about 1 x 104CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 1 x 104CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 1 x 106CFU / mL ART12 and / or ART24. In some embodiments, the edible products are inoculated with at least about 1 x 108CFU / mL ART12 and / or ART24. In some embodiments, compositions comprise at least about 1 x 109CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 1 x IO10CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 1 x 1011CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 1 x 1012CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 1 x 1013CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise at least about 1 x 1014CFU / mL ART12 and / or ART24. In some embodiments, the compositions comprise a total cell count (TCC) of ART12 and / or ART24 that would correspond to the CFU / mL amounts described herein. In some embodiments, the methods of the present technology involve the administration of about lxl09to about IxlO14viable bacteria or spores per day. In some embodiments, the methods of the present technology involve the administration of about lxl09to about IxlO12viable bacteria or spores per day. In some embodiments, the compositions of the present technology are delivered as lyophilized material or powder to be re-suspended for oral delivery or packaged into capsules. The lyophilized material and capsules may be coated for better enteric stability.

[0120] An exemplary treatment regimen entails administration once or twice per day. In therapeutic applications, a relatively high dosage at relatively short intervals is sometimes required until progression of the disease is reduced or terminated, or until the subject shows partial or complete amelioration of symptoms of disease. Thereafter, the subject can be administered a prophylactic regime. In some embodiments, compositions of the present technology are administered to a subject multiple times per day. In some embodiments, compositions of the present technology are administered to a subject once, twice, or three times per day or more for a certain period of time or until the subject is deemed cured of primary disease, not to be at risk for recurrence of primary disease, or not to be at risk for the disease. In some embodiments, the compositions of the present technology may beadministered to the subject for the remainder of the subject’s life. In some embodiments, administration is paired with an exposure to co-therapeutics (i.e., agents known in the art for the treatment of: MS, such as a disease-modifying agent; ASD, such as a course of therapy or a therapeutic agent for a co-occurring symptom, or agents known in the art for the treatment of social anxiety, such as psychotherapy, cognitive behavioral therapy, selective serotonin reuptake inhibitors (such as paroxetine or sertraline), serotonin and norepinephrine reuptake inhibitors (such as venlafaxine), anti-depressants, anti-anxiety medications, benzodiazepines, beta blockers; a tauopathy, such as anti-Tau antibodies, vaccines inducing immunity against tau, tau-disaggregation agents, anti-tau-expression agents, anti-amyloid plaque agents, anti-amyloid antibodies, modulators of Tau phosphorylation, modulators of Tau acylation, histone deacetylase inhibitors, modulators of Tau glycosylation, inhibitors of Tau glycosylation, modulators of Tau truncation, proteasome stimulators, USP14 inhibitors, phosphodiesterase inhibitors, autophagy activators, chaperone modulators, co-chaperone modulators, and Tau oriented multi-target directed ligands; HD, such as agents known in the art for the treatment of HD, such as olanzapine, pimozide, risperidone, fluphenazine, tetrabenazine, deuterabenazine, amantadine, levetiracetam, clonazepam, haloperidol, aripiprazole, quetiapine, citalopram, escitalopram, fluoxetine, sertraline, divalproex, carbamazepine, lamotrigine, antipsychotics, antidepressants, anticonvulsants, mood-stabilizing drugs, and anti-anxiety agents; or ALS: such as a disease-modifying agent known in the art for the treatment of ALS), either simultaneously, separately, or sequentially with once, twice, or three times daily dosing of the compositions of the present technology. In some embodiments, methods of prophylaxis comprise administration of compositions of the present technology once, twice, or three times daily.

[0121] The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to, the severity of the disease or disorder, previous treatments, the general health and / or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of the therapeutic compositions described herein can include a single treatment or a series of treatments.XI. Combination Therapy with ART12 and / or ART24

[0122] In some embodiments, the ART12 and / or ART24 strains of the present technology, or spores thereof, may be combined with each other or with one or more additional therapies for the prevention or treatment of MS, ASD and / or social anxiety, a tauopathy, HD, or ALS.

[0123] Additional therapeutic agents for the prevention or treatment of MS include, but are not limited to, one or more additional therapeutic agents selected from the diseasemodifying agents, which may include injectable medications (Avonex® (interferon betala), Betaseron® (interferon beta- lb), Copaxone® (glatiramer acetate), Extavia® (interferon beta- lb), Glatiramer Acetate Injection (glatiramer acetate -generic equivalent of Copaxone), Glatopa® (glatiramer acetate - generic equivalent of Copaxone 20mg and 40mg doses), Kesimpta® (ofatumumab), Plegridy® (peginterferon beta- la), Rebif® (interferon beta- la)), oral medications (Aubagio® (teriflunomide), Bafiertam™ (monomethyl fumarate), Dimethyl Fumarate (dimethyl fumarate - generic equivalent of Tecfidera), Gilenya® (fmgolimod), Mavenclad® (cladribine), Mayzent® (siponimod), Ponvory™ (ponesimod), Tecfidera® (dimethyl fumarate), Vumerity® (diroximel fumarate), Zeposia® (ozanimod)), and / or infused medications (Briumvi™ (ublituximab-xiiy), Lemtrada® (alemtuzumab), Novantrone® (mitoxantrone), Ocrevus® (ocrelizumab), and Tysabri® (natalizumab)).

[0124] Additional therapeutic agents for the prevention or treatment of ASD include, but are not limited to, one or more additional therapies selected from a course of therapy (e.g., talk therapy, discrete trial training, pivotal response training, speech and language therapy, occupational therapy, sensory integration therapy, physical therapy, social-relational training, and / or cognitive-behavior therapy) and therapies for co-occurring symptoms of autism spectrum disorder (e.g., risperidone, aripiprazole, or a combination thereof). Additional therapies for the prevention or treatment of social anxiety include, but are not limited to, one or more additional therapies selected from the group consisting of psychotherapy, cognitive behavioral therapy, selective serotonin reuptake inhibitors (such as paroxetine or sertraline), serotonin and norepinephrine reuptake inhibitors (such as venlafaxine), anti-depressants, anti-anxiety medications, benzodiazepines, and beta blockers.

[0125] Additional therapeutic agents for the prevention and treatment of a tauopathy include, but are not limited to, one or more additional therapeutic agents selected from anti- Tau antibodies, vaccines inducing immunity against tau, tau-disaggregation agents, anti-tau- expression agents, anti-amyloid plaque agents, anti-amyloid antibodies, modulators of Tau phosphorylation, modulators of Tau acylation, histone deacetylase inhibitors, modulators of Tau glycosylation, inhibitors of Tau glycosylation, modulators of Tau truncation, proteasome stimulators, USP14 inhibitors, phosphodiesterase inhibitors, autophagy activators, chaperone modulators, co-chaperone modulators, and Tau oriented multi-target directed ligands.

[0126] Additional therapeutic agents for the prevention and treatment of HD include, but are not limited to, one or more additional therapeutic agents selected from olanzapine, pimozide, risperidone, fluphenazine, tetrabenazine, deuterabenazine, amantadine, levetiracetam, clonazepam, haloperidol, aripiprazole, quetiapine, citalopram, escitalopram, fluoxetine, sertraline, divalproex, carbamazepine, lamotrigine, antipsychotics, antidepressants, anticonvulsants, mood-stabilizing drugs, and anti-anxiety agents.

[0127] Additional therapeutic agents for the prevention and treatment of ALS include, but are not limited to, one or more additional therapeutic agents selected from the diseasemodifying agents, which may include riluzole (Rilutek®, Tiglutik™, Exservan™), tofersen (QALSODY™), sodium phenylbutyrate and taurursodiol (RELYVRIO™), dextromethorphan / quinidine (Nuedexta®), and edaravone (Radicava®), mecasermin, baclofen (Lioresal®), diazepam (Valium®), dantrolene (Dantrium®), nonsteroidal antiinflammatory agents, and / or anticonvulsive medications, such as carbamazepine (Tegretol) or phenytoin (Dilantin®), amitriptyline (Elavil®), nortriptyline (Pamelor™), or Lorazepam (Ativan®).

[0128] In some embodiments, an additional therapeutic agent is administered to a subject in combination with the ART12 and / or ART24 strain of the present technology, or spores thereof, such that a synergistic therapeutic effect is produced. For example, administration of ART24 and / or ART12 with one or more additional therapeutic agents for the prevention or treatment of MS, ASD and / or social anxiety, a tauopathy, HD, or ALS, will have greaterthan additive effects in the prevention or treatment of the disease and / or one or more of its signs or symptoms.

[0129] In some embodiments, a synergistic therapeutic effect is produced by the combined administration of a composition comprising ART24 and a composition comprising ART 12, either simultaneously, sequentially, or separately to the subject. In some embodiments, a synergistic therapeutic effect is produced by administration of a composition comprising ART24 and ART12 to the subject.

[0130] In any case, the multiple therapeutic agents may be administered in any order or even simultaneously. If simultaneously, the multiple therapeutic agents may be provided in a single, unified form, or in multiple forms (by way of example only, either as a single pill or as two separate pills). One of the therapeutic agents may be given in multiple doses, or both may be given as multiple doses. In addition, the combination methods, compositions and formulations are not to be limited to the use of only two agents.XII. Kits

[0131] The following discussion is presented by way of example only, and is not intended to be limiting.

[0132] In some embodiments, the present disclosure provides for a kit useful for treating MS, ASD and / or social anxiety, tauopathies, HD, or ALS, comprising a composition comprising a bacterial strain selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088), and a package insert with instructions for treating MS, ASD and / or social anxiety, tauopathies, HD, or ALS in a subject in need thereof. In some embodiments, the composition comprises ART12, ART24, or both ART12 and ART24. In some embodiments, the bacterial strain(s) is concentrated at about IxlO8colony forming units (CFU) per ml to about IxlO14CFU per ml of ART24 and / or ART12 bacterium (i.e., vegetative cell) or bacterial spore, or any amounts or concentrations or ranges thereof disclosed herein. In some embodiments, the package insert instructs that about IxlO9to about IxlO14viable bacteria or spores be administered per day, or any amount of viable bacteria or spores disclosed herein. In some embodiments, the compositions of the kit are delivered as lyophilized material or powder to be re-suspendedfor oral delivery or packaged into capsules. The lyophilized material and capsules may be coated for improved enteric stability. In some embodiments, the bacterial strain(s) is lyophilized. The compositions of the kit may be formulated in effective amounts (i.e., amounts that have desired therapeutic effect). The dose and dosage regimen will depend upon the type or degree of MS progression, ASD and / or social anxiety, tauopathy, the HTT mutation associated with the case of HD, the degree and / or progression of HD, the degree of ALS, and symptom severity in the subject, the characteristics of the ARTT2 and / or ART24 strain used, e.g., its therapeutic index, the subject, and the subject’s history. The effective amount may be determined during pre-clinical trials and clinical trials by methods familiar to physicians and clinicians, and instructions regarding the effective amount can be included on the package insert.

[0133] In some embodiments, the kit further comprises a co-therapeutic. In some embodiments, the co-therapeutic comprises one or more disease modifying agents or treatments for a co-occurring symptom, such as, but not limited to, those described herein. In some embodiments, the package insert instructs that the co-therapeutic be provided simultaneously, sequentially, or separately to the bacterial strain(s). In some embodiments, the kit further comprises other materials useful for treating MS, ASD and / or social anxiety, tauopathies, HD, or ALS, such as containers (e.g., bottles, vials, syringes, etc.), additional buffers or solutions (e.g., saline, PBS, or cleaning solutions), additional instructions regarding combination therapies, and memory aids (e.g., a calendar insert to remind a subject to take a dose as instructed).

[0134] In some embodiments, the package insert instructs that the bacterial strain(s) be administered daily, twice daily, or three times daily, or at any dosage regimen disclosed herein. In some embodiments, the package insert instructs that the bacterial strain(s) be administered orally, buccaly, rectally, or sublingually. In some embodiments, the package insert instructs that the bacterial strain(s) be added to a food or beverage. In some embodiments, the package insert instructs that the MS, ASD and / or social anxiety, tauopathy, HD, or ALS symptoms of a subject receiving the bacterial strain(s) be tracked during the period of treatment.EXAMPLES

[0135] The following examples are provided by way of illustration only and not by way of limitation. Those of skill in the art will readily recognize a variety of non-critical parameters that could be changed or modified to yield essentially the same or similar results. The examples should in no way be construed as limiting the scope of the present technology, as defined by the appended claims.Materials and MethodsA. Multiple Sclerosis Model and Experimental Design

[0136] Multiple sclerosis (MS) was modeled in C57BL / 6 mice (N = 44). A separate group of naive control mice (N = 12) were left untreated throughout the experiment. MS was modeled using the myelin oligodendrocyte glycoprotein (MOG)-induced experimental allergic encephalomyelitis (EAE) method, which is well known to those in the art. EAE is a central nervous system autoimmune demyelinating disease that mimics many of the clinical and pathologic features of MS. The MOG murine model consists of a sensitization period, induced by the single subcutaneous injection of 200pl / animal MOG emulsified in Complete Freund’s adjuvant (CFA) (200 pg MOG / 300 pg CFA) on Study Day 0, followed by intraperitoneal supplemental immune-stimulation with pertussis toxin (PT) at 300ng / mouse carried out once at the day of EAE induction (study day 0) and once again 48 hours later (on study day 2).Table 1: Test Groups and Treatment Regimens

[0137] FIG. 1 shows a schematic of the experimental design used to test the efficacy of ART 12 and ART24 treatment in a mouse model of MS. The experiment used 5 treatment groups, as shown in Table 1 above. The arrow at study day 0 in FIG. 1 shows that treatment groups 2-5 were inoculated with MOG and CFA subcutaneously at study day zero. As shown by the circles, PT was injected intraperitoneally into treatment groups 2-5 at study days 0 and 2. The hexagons in row A indicate days where treatment group 3 was dosed once orally with the positive control FTY720, also known as fmgolimod, which is a disease modifying agent that functions as an immunomodulator and is used to treat multiple sclerosis (study days 0-23). The hexagons in row B indicate days where treatment groups 2 and 4-5 were dosed twice orally with PBS, ART 12, and ART24 respectively (study days 0- 23). The hexagons in row C indicate the study days where clinical observations were recorded (study days 0 and 8-24). The lightning bolts indicate that electrophysiology experimentation was performed at study day 0 (baseline data), study day 12, and study day 24.B. MS Disease Severity Clinical Scoring

[0138] All animals were examined for signs of any neurological responses and symptoms before EAE induction (study day 0) and thereafter examined daily from study days 8-24. EAE reactions are scored and recorded according to a 0-5 scale in Table 2 below, as described in Weaver, A. et a!., “An elevated matrix metalloproteinase (MMP) in an animal model of multiple sclerosis is protective by affecting Thl / Th2 polarization,” The FASEB Journal, 19: 1668-1670 (2005). The clinical score is determined by summing the score from each section of the scale.Table 2: EAE Disease Severity Scoring ScaleC. Electrophysiology for MS Analysis

[0139] Electrophysiology measurements were taken at study days 0, 12, and 24. At study day 0, before treatment groups were assigned, 15 mice were selected for analysis to provide a baseline data point for all measurements. At study days 12 and 24, electrophysiology measurements were taken from all mice in each treatment group, including motor evoked potential duration and sub-peak number.

[0140] To measure motor evoked potentials, mice were first anesthetized with intraperitoneal injection of ketamine (85 mg / kg) and xylazine (15 mg / kg) prior to the placement of subcutaneous electrodes (0.2 mm diameter) for the recording of evoked potentials. Prior to any stimulation, the depth of anesthesia was verified by loss of toe pinch reflex and eye reflex. Recordings were performed during the first 10-25 min after injection of anesthesia. A NIM Eclipse I0NM System (Medtronic) was used for triggering stimulation and recording evoked potentials.

[0141] For motor evoked potential (MEP) recordings, the active needle electrode was inserted into the gastrocnemius muscle, and the reference electrode was inserted into the ankle along the tibial nerve pathway. For motor stimulation, two electrodes were inserted above the right and left motor cortices, 2.0mm lateral to the sagittal suture line and 0.5mm rostral from posterior bregma. The ground electrode was inserted into the base of mouse tail. MEP duration and sub-peak number were measured.D. 3-Chamber Test Experimental Design for ASD Model

[0142] Autism Spectrum Disorder (ASD) was modeled using the commonly accepted BTBR mouse model (BTBR T Itpr3tf / J), which exhibits various symptoms of ASD, including reduced social behavior, increased repetitive behavior, and abnormal brain structures and activities that are comparable to those observed in human subjects with ASD. The 3-chamber test experiment was used to measure the impact of ART24 treatment on the behavioral symptoms of ASD in the BTBR mouse model. As shown in FIG. 5, the test was carried out in two 3-chamber boxes in Plexiglas (60 cm long, 40 cm large, 35 cm high).Boxes were divided in three compartments (chambers) of the same dimension by walls with small square openings (5 x 3 cm) allowing access into each chamber. Four plastic cylinders(20 cm high, 10 cm diameter) in which an object or a mouse can be enclosed, were placed in the corner of the left side and right side chambers.E. Sociability and Social Novelty Preference for Social Anxiety and ASDAnalysis

[0143] Using the 3-chamber experimental design described above, the impact of ART24 treatment on the sociability and social novelty preference of BTBR mice was examined. The three experimental groups, represented below in Table 3, included C57-Control mice (N=16, C57BL / 6 mice), BTBR-Control mice (N=16), and BTBR-ART24 mice (N=16). C57BL / 6 mice are highly sociable and are commonly used as a control in BTBR mice experiments. (Meyza et. al., 2017). C57-Control mice and BTBR-Control mice both received vehicle (PBS) orally twice daily (p.o.), while BTBR-ART24 mice were treated with 5xl08colony forming units (CFU) of ART24 (resuspended from lyophilization in PBS) orally twice daily. Both groups were treated a total of 13 times over 7 days and the 3- chamber experiments were performed after the final treatment.Table 3: Treatment Groups

[0144] Sociability testing began with habituating all mice to their environments. Stimulus mice were habituated to the plastic cylinders (see FIG. 5) by enclosing them in the cylinders for three 30-minute sessions on either two or three consecutive days before beginning the experiment. Treatment group mice were habituated to the 3 -chambers by placing them in the center compartment for 5 minutes with doors closed and then removing the doors and allowing them to explore all areas of the container for an additional 10 minutes. After treatment group mice habituation they were returned to the center compartment and cylinders were placed into the comers of each side of the container. A stimulus mouse (C57BL / 6J mouse of the same gender (male) and the same age as treatment group mice) was placed into one of the cylinders and an object (4^4x4 cm dark coloredcube) was placed into another. The location of the stimulus mouse and the object was pseudo-randomized for all treatment groups such that the stimulus mouse was placed on one side of the chamber for half of the treatment group mice and on the other side of the chamber for the other half of the treatment group mice. Once the stimulus mouse and object were in place, the doors to the center compartment were removed and the treatment group mice were allowed to explore the chamber for 10 minutes. During the exploration period, the time spent in each compartment, time spent in proximity to each cylinder, the total distance traveled, and the time spent exploring (sniffing) the object / stimulus mouse was measured.

[0145] After the sociability experiment, the treatment group mice were returned to the center compartment. To test social novelty, the object was replaced by a novel stimulus mouse. The former stimulus mouse was maintained in the same location. The doors to the center compartment were then removed and the treatment group mice were allowed to explore the chamber for ten minutes. During the exploration period, the time spent in each compartment, time spent in proximity to each cylinder, the total distance traveled, and the time spent exploring (sniffing) the novel stimulus mouse / familiar stimulus mouse was measured.F. Tauopathy Model and Experimental Design

[0146] Tauopathies were modeled using a mutagenesis-screening based approach in zebrafish (Danio rerio). Wild type AB zebrafish were acclimated to standard aquaculture conditions (14 hours light, 10 hours dark, 28 + / - 1°C, pH 6.8-7) for two weeks. Then the forward genetic method, as described by Driever W, et. al., A genetic screen for mutations affecting embryogenesis in zebrafish, Development, 123:37-46, (1996), was used to generate Tau mutants. Briefly, adult male zebrafish were mutagenized via ENU treatment and then allowed to spawn. Fl progeny were genetically screened and stable heterozygous founder fish with mutants to the Tau gene were identified and used to breed homozygous Tau mutant experimental fish with a MAPT (gene ID: 567833) mutation resulting in a truncated Tau protein at amino acid 282. Tauopathy embryos were maintained in standard embryo media, and embryos with a healthy growth phase at 4 days post fertilization were selected for the study. Throughout the study the fish were housed in 25 liter tanks with nomore than 80 fish per tank to avoid any crowding effects. Fish were separated into six study groups, as shown in Table 4 below.Table 4: Study Groups and Dosing

[0147] All treatments were added directly to tank water with 24 hour washout cycles, such that tank water was fully replaced every 24 hours. Positive control fish were treated with KU0063794, an mTor inhibitor which is known to promote clearance and degradation of Tau aggregates. Study groups received treatment on 6 days post fertilization (DPF), 7 DPF, and 8 DPF, with ROS and mobility assays occurring on 9 DPF.G. Open Field Test for Mobility in Tauopathy Model

[0148] Each study group was subjected to an open field test (n=24). Larvae were transferred to a 24-well plate in embryo media at a distribution of 1 larvae per well. The plate was backlit and video of each well was recorded at 720p and 30 fps for ten minutes. Videos were processed using ImageJ and analyzed using the object tracking software Mtrack2.H. Reactive Oxygen Species (ROS) Assay for Tauopathy Analysis

[0149] All study groups were examined for total ROS production in brain cells using a spectrophotometry assay kit (Sigma MAK143-1KT). At 9 DPF three larvae per study group were randomly selected, euthanized, and the larval brains were isolated. Brain tissue was homogenized in 50 pl water, normalized to an O.D. of 0.6, and incubated with the reaction master mix (100 pl ) for 20 minutes at 37°C. Samples were read using a spectrophotometer from 600nm to 500nm and MetaSpec was used to analyze the data.I. Huntington ’s Disease Model and Experimental Design

[0150] Huntington’s Disease (HD) was modeled using a mutagenesis-screening based approach in zebrafish (Danio rerio). Wild type AB zebrafish were acclimated to standard aquaculture conditions (14 hours light, 10 hours dark, 27 + / - 1°C, pH 7.2-7.4) for one week. Then the forward genetic method, as described by Driever W, et. al., A genetic screen for mutations affecting embryogenesis in zebrafish, Development, 123:37-46, (1996), was used to generate HTT mutants. Briefly, adult male zebrafish were mutagenized via ENU treatment and then allowed to spawn. Fl progeny were genetically screened and stable heterozygous founder fish with mutants to the HTT gene were identified and used to breed homozygous mutant experimental fish with a K32Q- / - HTT (gene ID: 30214) mutation, which results in a triple glutamine repeat. The K32Q- / - HD model fish (mHD) exhibited many of the signs and symptoms associated with HD in humans, including decreased expression of the striatal neuron-specific receptor GPR88, random jerky movements (chorea), aggressive behaviors (e.g., wall-butting), and a fourfold increase in cerebrospinal fluid Neurofilament Light chain (Nfl) levels (data not shown). For a discussion of Nfl as an HD marker, see Byrne LM et al., Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis Lancet Neurol. 2017 Aug;16(8):601-609. mHD embryos were maintained in standard embryo media, and embryos with a healthy growth phase at 4 days post fertilization were selected for the study. Throughout the study, the fish were housed in 25 liter tanks with no more than 80 fish per tank to avoid any crowding effects. Fish were randomly separated into 6 study groups, at 5 days post fertilization (DPF) as shown in Table 5 below.Table 5: Study Groups and Dosing

[0151] All treatments were added directly to tank water with 24 hour washout cycles, such that tank water was fully replaced every 24 hours with fresh treatment and water. Tetrabenazine is an approved therapeutic for treating chorea in humans, but has not been shown to inhibit neuronal degeneration or improve mobility independent of the reduction in chorea. Study groups received treatment on 6 DPF, 7 DPF, and 8 DPF, with all disease phenotype assays occurring on 9 DPF.J. Chorea Assay for Huntington ’s Disease Model

[0152] Each study group (n=9) was subjected to a well assay for chorea, as measured via number of involuntary jerky movements. Larvae were transferred to a 24-well plate in embryo media at a distribution of 1 larvae per well and were acclimated to well conditions for 10 minutes. Then a stereomicroscope was used to observe larvae in motion and the total number of jerky movements per minute was tracked.K. Open Field Mobility Assay for Huntington ’s Disease Model

[0153] Each study group will be subjected to an open field test for mobility. Larvae will be transferred to a 24-well plate in embryo media at a distribution of 1 larvae per well. The plate will be backlit and video of each well will be recorded for a period of time. Videos will be processed using ImageJ and analyzed using the object tracking software Mtrack2. Mobility will then be quantified, including via total time in motion per minute and total swim distance per minute.L. Striatal Neurodegeneration for Huntington ’s Disease Model

[0154] Each study group will be examined for striatal neurodegeneration. At 9 DPF larvae will be sedated with 0.03% Tricane for 3 minutes until movement ceases. The sub pallium portion of the brain will be isolated and tissue will be used to prepare cytology slides. Cells will be stained with various markers for degeneration and cellular integrity, such as hematoxylin and eosin. Cytology images will be taken using a light microscope and percent striatal degeneration will be computed using a software program such as Qupath.M. ALSModel

[0155] To recapitulate pathological and functional disease progression, a zebrafish (Danio rerio) larvae amyotrophic lateral sclerosis model (ALS) was developed by ENU (N-ethyl- N-nitrosourea) mutation of gene TDP43' / _. In this study, bacterial agents, ADS024 and ADS012, in different combinations and standard drug Riluzole were screened in the TDP43" / _ALS model. The study focused on determining the efficacy of the test compounds in operculum movements per min and buccal movements per min.N. Zebrafish husbandry for ALS Model

[0156] Wild type (WT) strains of zebrafish were used in this study. The fishes were well adapted and bred. The fish were acclimatized to standard optimal laboratory conditions (14h light: lOh darkness photoperiod, diet, water, 27±1°C) for at least one week in stock aquaria before initiating the experiments. The fish were fed with Tetrabit flakes (a complete pet food for tropical fish from Tetra GmbH, Herrenteich) three times daily. All the fish used in the study were random zebrafish larvae obtained from different clutches.

[0157] A group of 24 adult fish were housed in transparent polycarbonate tanks at light / dark cycle of 14 / 10 h with water temperature of 27 ± 1°C and pH between 7.2-7.4. Good Animal Practice as per Institutional Animal Ethics Committee and in accordance with Committee for the Purpose of WT and Supervision of Experiments (CPCSEA), India, were followed. Housing tanks were cleaned once in 4 days to keep the fishes clean and free from infection. The eggs collected from the conditioned adults were housed and maintained in embryo medium, and after 5 days post-fertilization (dpf) larvae were fed three times daily according to a larvae maintenance schedule.O. Chemicals for ALS study

[0158] All the chemicals purchased for the study were of analytical grade. Chemicals used in the study are as follows: Riluzole (R116-25MG), Sigma-Aldrich, methylcellulose (9004- 67-5) Sigma-Aldrich.P. TDP43~ ~ ALS model induction

[0159] For model induction, the forward genetic method as per Driever et al., Development 123:37-46 (Dec. 1996) was employed. Adult male zebrafish were subjected to ENU chemical mutagen at a dosing concentration of 5mM through water dissolution method to induce random mutagenesis. Prior to the spawning, the ENU induced male zebrafish and WT adult females (herein referred to as zebrafish founders) were housed separately under standard laboratory husbandry conditions. Zebrafish founders were set for spawning at a spawning ratio of 1 :4 i.e., 1 female to 4 male fish per breeding tank. The generated pool of Fl mutants were screened for phenotype and genotype. Genotyping was performed through fin clips and TDP43+ / 'ALS mutants were identified (Gene ID: 325052). The Fl mutants carrying the TDP43+ / " mutation were inbred and the resulting F2 embryos (henceforth addressed as TDP43' / _) were employed for this study. Sperm from TDP43' / _fish were collected and cryopreserved by following the method described by Morris et al., Biotechniques 35(5):956-958 (2003) to recover TDP43' / _fish as per experimental necessity.Q. TDP43~ ~ ALS model screening

[0160] To validate the model, 5 dpf F2 progeny were phenotypically screened for reduced operculum movement and bradykinesia.R. Group setting for ALS Model

[0161] Following model screening, the larvae that showed positive bradykinesia were transferred to experimental study groups. Group setting was performed at 6 dpf with a distribution pattern of 24 larvae per group for the following classes: Group 1-WT, Group 2- TDP43' / 'ALS model, Group 3- TDPdS'^ALS model treated with standard drug Riluzole - lOuM, and test compounds Group 4-ADS024 -2E7 TCC / ml, Group 5-ADS012 -2E7 TCC / ml, Group 6-ADS024-1E7 TCC / ml +ADS012 -1E7 TCC / ml, Group 7-ADS024-2E7 TCC / ml +ADS012-2E7 TCC / ml at the desired dilutions of the test compounds.S. Dosing for ALS Model

[0162] The study doses were determined from the previous studies conducted with the test compounds as shown in Table 6. Study groups to be treated with test compounds were dosed on 6 dpf, 7 dpf, and 8 dpf with 24 h washout cycle. The reconstituted stockconcentrations of Riluzole were stored in single-use Eppendorf tubes at -20°C, thawed and used for preparing the desired working concentrations when required. Continuous screening was performed for behavioral and phenotype changes and the respective findings were recorded for further analysis. Translational dosing concentration of 10 pM was obtained from a previous study by McGown el al., Mol. Neurodegener. 11 ( 1 ): 56 (Jul. 2016).Table 6: Dosing of test compoundsTCC = total cell countT. Water dissolution dosing for ALS Model

[0163] The test compounds were administered by water dissolution where the respective quantity of the compound was added to the water in which the larvae were housed. The working stocks of the test compounds were prepared as follows. To make a stock of 1000X for ADS024, one vial containing 1.23 x IO10TCC / vial was resuspended in 1.23 mL water for fish to create a solution of 1 x IO10TCC / mL. To make a stock of 1000X for ADS012, one vial containing 9.62 x 109TCC / vial was resuspended in 0.962 mL water for fish to create a solution of 1 x IO10TCC / mL. A homogenous mixture of the working stocks was used for dose administration. The respective concentration of the dose was administered to the study housing tanks as per the dosing timelines on 6, 7, and 8 dpf. Washout wasperformed once in 24h before dose administration. The water dissolution groups of WT and TDP43' / _ALS larvae groups were treated under similar housing conditions as that of the study groups.U Washout for ALS Model

[0164] Throughout the study period, larvae were monitored for alterations in the behavioral pattern. Larvae were housed at temperature (25 ± 1°C) to aid the physiological changes. A 24 h washout cycle was precisely followed to eliminate the probability of mortality and improve the survival odds.Example 1 : ART12 and ART24 Improve Multiple Sclerosis Model Disease Severity Clinical Scoring

[0165] This example demonstrates that ART 12 and ART24 are useful in methods for treating MS by reducing or ameliorating symptom severity.

[0166] Using the methods described above, the ART24 and ART12 strains were tested for their ability to ameliorate or reduce MS symptom severity based on EAE scoring. FIG. 2 shows that animals treated with vehicle alone showed a gradual elevation in their EAE clinical score, as expected from disease progression. FIG. 2 further shows that ART24 significantly reduced the severity of disease versus the vehicle control group, and ART12 similarly reduced disease severity. These results indicate that treatment with either ART24 or ART12 is sufficient to ameliorate or reduce MS symptom severity. The results shown in FIG. 2 are reproduced in Table 7 below (#p<0.05 vs. treatment group 2 (vehicle),###p<0.001 vs. treatment group 2, and####p<0.0001 vs. treatment group 2, all performed using one-way ANOVA followed by Dunnett’s test).Table 7: Group Mean EAE Clinical Score

[0167] Accordingly, these results demonstrate that both ART12 and ART24 are capable of reducing or ameliorating the severity of symptoms in a model for multiple sclerosis, and are therefore useful in methods for treating MS.Example 2: ART12 and ART24 Improve Multiple Sclerosis Model Motor Evoked Potential (MEP) Electrophysiology

[0168] This example demonstrates that ART12 and ART24 improve the MEP electrophysiology in a mouse model of MS, and are therefore useful in methods for treating MS.

[0169] Using the methods described above, the ART24 and ART12 strains were tested for their ability to improve MEP electrophysiology in a mouse MS model. More specifically, MEP duration and number of sub-peaks were measured at baseline and for all treatment groups at study days 12 and 24.

[0170] Increased MEP durations indicate desynchronization of signal transduction in mild disease. In severe disease stages, the unsynchronized fibers tend to die and disappear.Since in this experiment animals were only in the mild-disease range, longer signal duration is an indication of disease progression. As shown in FIG. 3, at Study Day 12 all treatment groups except Naive mice exhibited elevated MEP duration compared to baseline, with the vehicle treatment group and the positive control FTY720 treatment group exhibiting significantly longer durations (p<0.05). By Study Day 24, ART12- and ART24-treatedmice exhibited a significant decrease in MEP duration relative to the vehicle treatment group, resulting in an MEP duration that was comparable to those observed in baseline mice, naive mice, and positive control FTY720-treated mice. This is consistent with either an improvement in synchronization of signal, or a decrease in unsynchronized fibers in the ART12 and ART24 treated mice. The results shown in FIG. 3 are reproduced in Table 8 below (* p<0.05 compared to baseline, **** pO.OOOl compared to baseline, $$ p<0.01 compared to treatment group 1, and ### p<0.001 compared to treatment group 2, all performed using a one-way ANOVA followed by Dunnett’s test).Table 8: Average MEP Duration

[0171] An increase in the total number of MEP sub-peaks also indicates desynchronization of signal transduction in mild MS disease. As shown in FIG. 4, while there was no significant difference between any of the treatment groups at study day 12, by study day 24 ART 12 and ART24 treatment reduced total sub-peak numbers compared to vehicle treatment. This is consistent with either an improvement in synchronization of signal, or a decrease in unsynchronized fibers, due to ART 12 and ART24 treatment. The results of FIG. 4 are reproduced in Table 9 below (* p<0.05 compared to baseline, **** p<0.0001 compared to baseline, $ p<0.05 compared to treatment group 1, and ## p<0.01 compared to treatment group 2, all statistics performed using a one-way ANOVA followed by Dunnett’s test).Table 9: Average Sub-Peak Number

[0172] Taken together, the MEP electrophysiology results demonstrate that treatment with either ART 12 or ART24 results in improved MEP electrophysiology in an MS model, as compared to the vehicle control group. In combination with the demonstrated reduction in clinical disease severity scoring, these results demonstrate that the ART12 and ART24 strains of the present technology are useful in methods for the treatment of multiple sclerosis.Example 3: ART24 Strain Improves Sociability in Autism Spectrum Disorder Model

[0173] This example demonstrates that the ART24 strain of the present technology is useful in methods for treating ASD and / or social anxiety by reducing or ameliorating symptom severity. In particular, this example demonstrates that ART24 treatment improves sociability in a mouse model for ASD and social anxiety.

[0174] Using the methods described above, the ART24 strain was tested for its ability to improve sociability in a mouse model for ASD and social anxiety. FIGs. 6A-6B show that C57-Control mice exhibited a significant preference for exploring the stimulus mouse (Cong) over the object during the first 5 minutes of exploration (FIG. 6A) and the total 10 minutes of exploration (FIG. 6B). FIGs. 6A-6B also show that the BTBR-Control mice had no significant preference between the stimulus mouse and the object during the first 5 minutes of exploration (FIG. 6A) and the total 10 minutes of exploration (FIG. 6B). Both results are consistent with neurotypical mouse behavior and the behavior of the ASD-model BTBR mice. FIGs. 6A-6B further show that ART24 treatment of BTBR mice lead to a significant preference for exploring the stimulus mouse over the object during the first 5 minutes of exploration (FIG. 6A) and the total 10 minutes of exploration (FIG. 6B). This result indicates improved sociability in BTBR mice from ART24 treatment as compared to the BTBR control mice. The results shown in FIGs. 6A-6B are reproduced in Table 10 below, wherein the p vs. random row shows the results of an unpaired Student’ s t-test comparing time spent exploring the stimulus mouse (Cong) to time spent exploring the object (Obj).Table 10: Sociability - Exploration Results

[0175] Additionally, FIGs. 7A-7B show the percentage of time each treatment group spent exploring the stimulus mouse (congener) out of total time spent exploring the stimulus mouse and the object. As shown in FIGs. 7A-7B, C57-Control mice spent a significantly higher percentage of time exploring the stimulus mouse as compared to the BTBR-Control mice and as compared to a 50% baseline value during the first 5 minutes of exploration time (FIG. 7A) and during the total 10 minutes of exploration time (FIG. 7B). FIGs. 7A-7B also show that BTBR-Control mice did not spend a significantly different percent of time exploring the stimulus mouse as opposed to a 50% baseline value during the first 5 minutes of exploration time (FIG. 7A) and during the total 10 minutes of exploration time (FIG. 7B). In contrast to the BTBR-Control mice, FIGs. 7A-7B show that BTBR-ART24 mice spent a significantly higher percentage of time exploring the stimulus mouse as compared to a 50% baseline value during the first 5 minutes of exploration time (FIG. 7A) and exhibited a strong preference for the stimulus mouse during the total 10 minutes of exploration time (FIG. 7B). Additionally, there was no significant difference between the exploration time percentages of the C57-Control mice and the BTBR-ART24 mice during the first 5 minutes of exploration time (FIG. 7A) and during the total 10 minutes of exploration time (FIG. 7B). Taken together, these results demonstrate that treatment with ART24 is sufficient to ameliorate the impaired sociability observed in subjects with ASD and social anxiety. The results shown in FIGs. 7A-7B are reproduced in Table 11 below, wherein the p vs. randomrow shows the results of an unpaired Student’ s t-test comparing the percent of time spent exploring the stimulus mouse (congener) to a 50% baseline.T able 11: Sociability - Exploration Percentage Results

[0176] In addition to the improved sociability exploration results, ART24 treatment also led to increasingly social behavior in terms of strong positive trends towards increased time spent in stimulator mouse compartments and in proximity to stimulator mouse cylinders (data not shown).

[0177] Accordingly, these results demonstrate that treatment with ART24 can reduce or ameliorate the severity of symptoms in a model for Autism Spectrum Disorder and social anxiety, and therefore the ART24 strain of the present disclosure is useful in methods for treating ASD and / or social anxiety.Example 4: ART24 Strain Improves Social Novelty Preference in Autism Spectrum Disorder Model

[0178] This example demonstrates that the ART24 strain of the present technology is useful in methods for treating ASD and / or social anxiety by reducing or ameliorating symptom severity. In particular, this example demonstrates that ART24 treatment improves social novelty preference in a mouse model for ASD and social anxiety.

[0179] Using the methods described above, the ART24 strain was tested for its ability to improve social novelty preference in a mouse model for ASD and social anxiety. FIGs. 8A-8B show that C57-Control mice exhibited a significant preference for exploring a novel stimulus mouse (Novel) over a familiar stimulus mouse (Famil) during the first 5 minutes of exploration (FIG. 8A) and the total 10 minutes of exploration (FIG. 8B). FIGs. 8A-8B also show that the BTBR-Control mice had no significant preference between the novel stimulus mouse and the familiar stimulus mouse during the first 5 minutes of exploration (FIG. 8A) and the total 10 minutes of exploration (FIG. 8B). Both of these results are consistent with neurotypical mouse behavior and the behavior of the BTBR mice. FIG. 8A further shows that ART24 treatment of BTBR mice lead to a significant preference for exploring the novel stimulus mouse over the familiar stimulus during the first 5 minutes of exploration. This is consistent with an improved preference for social novelty resulting from ART24 treatment. The results shown in FIGs. 8A-8B are reproduced in Table 12 below, wherein the p vs. random row shows the results of an unpaired Student’ s t-test comparing time spent exploring the novel mouse versus the familiar mouse.Tab e 12: Social Novelty Preference - Exploration Results

[0180] Additionally, FIGs. 9A-9B show the percentage of time each treatment group spent exploring the novel stimulus mouse (novel congener) out of total time spent exploring the novel stimulus mouse and the familiar stimulus mouse. As shown in FIGs. 9A-9B, C57-Control mice spent a significantly higher percentage of time exploring the novelstimulus mouse as compared to a 50% baseline value during the first 5 minutes of exploration time (FIG. 9A) and during the total 10 minutes of exploration time (FIG. 9B). FIGs. 9A-9B also show that BTBR-Control mice did not spend a significantly different percent of time exploring the novel stimulus mouse as opposed to a 50% baseline value during the first 5 minutes of exploration time (FIG. 9A) and during the total 10 minutes of exploration time (FIG. 9B). In contrast to the BTBR-Control mice, FIG. 9A shows that BTBR-ART24 mice spent a significantly higher percentage of time exploring the novel stimulus mouse as compared to a 50% baseline value during the first 5 minutes of exploration time. Taken together, these results indicate that treatment with ART24 is sufficient to ameliorate the impaired social novelty preference observed in subjects with ASD. The results shown in FIGs. 9A-9B are reproduced in Table 13 below, wherein the p vs. random row shows the results of an unpaired Student’s t-test comparing the percentage of time spent exploring the new stimulus mouse and a 50% baseline value.Table 13: Social Novelty Preference - Exploration Percentage Results

[0181] In addition to the improved social novelty preference exploration results, ART24 treatment also lead to increased preference for social novelty as indicated by strong positive trends towards increased time spent in novel stimulator mouse compartments and in proximity to novel stimulator mouse cylinders (data not shown).

[0182] Accordingly, these results demonstrate that treatment with ART24 can reduce or ameliorate the severity of symptoms in a model for Autism Spectrum Disorder, andtherefore the ART24 strain of the present disclosure is useful in methods for treating ASD and / or social anxiety.Example 5: Behavioral Improvements of BTBR mice treated with ART24 are not Attributable to Changes in Locomotion or Immune Response

[0183] This example demonstrates that the improvements observed in ASD and social anxiety model mice resulting from treatment with the ART24 strain of the present technology are not attributable to changes in locomotion. In particular, this example demonstrates that ART24 treatment does not significantly impact mouse locomotion.

[0184] Total locomotion of all treatment group mice was tracked throughout the 3- chamber experiments, including during the habituation period, the sociability experiments, and the social novelty experiments. As shown in FIG. 10, there was no significant difference between total distance travelled by BTBR-Control mice and BTBR-ART24 mice during any period. Therefore, the improvements to social behavior observed upon ART24 treatment are not attributable to altered locomotion. The results shown in FIG. 10 are reproduced in Table 14 below.Table 14: Total Distance Traveled

[0185] These results show that treatment with ART24 can reduce or ameliorate the severity of symptoms in a model for Autism Spectrum Disorder and / or social anxiety, and that the treatment effect is not attributable to altered locomotion capacity. Accordingly, theART24 strain of the present disclosure is useful in methods for treating ASD and / or social anxiety.Example 6: ART12 and ART24 Decrease Brain ROS Levels in Tauopathy Model

[0186] This example demonstrates that ART 12 and ART24 are useful in methods for treating tauopathies by reducing or ameliorating ROS production in the brain.

[0187] Increases to ROS levels in the central nervous system is an early marker of tauopathies. Additionally, disease pathology is directly proportional to ROS levels, with increased ROS levels associated with increased disease severity. Using the methods described above, the ART24 and ART 12 strains were tested for their capacity to ameliorate or reduce ROS production in the brain in a tauopathy model. FIG. 11 shows that treatment with either ART12 or ART24 alone was sufficient to significantly reduce ROS levels as compared to the untreated Tauopathy group. ART12 / 24 combination treatment reduced ROS levels to WT amounts and displayed a synergistic treatment effect, with an even greater reduction in ROS levels than was observed in the positive control, ART12, or ART24 treatment groups. The results shown in FIG. 11 are reproduced in Table 15 below.Table 15: Brain ROS Production

[0188] Accordingly, these results demonstrate that both ART12 and ART24 are capable of reducing or ameliorating ROS production in the brain in a model for tauopathies, and are therefore useful in methods for treating tauopathies.Example 7: ART 12 and ART24 Improve Mobility in a Tauopathy Model

[0189] This example demonstrates that ART 12 and ART24 improve mobility in a model for tauopathy, and are therefore useful in methods for treating tauopathies.

[0190] Using the methods described above, the ART24 and ART12 strains were tested for their capacity to improve mobility in a model of tauopathy. Decreased mobility due to neuronal degradation is associated with tauopathy progression. As shown in FIG. 12, fish treated with either ART12 or ART24 alone swam a significantly greater distance per minute than the tauopathy group. Additionally, and as observed in Example 1, treatment with ART12 and ART24 produced a synergistic effect and enhanced swimming distance to an even greater degree than in the positive control, ART 12 alone, or ART24 alone treatment groups. The results shown in FIG. 12 are reproduced in Table 16.Table 16: Average Swimming Distance per Minute

[0191] These results demonstrate that treatment with either ART 12 or ART24 results in improved mobility in a tauopathy model. In combination with the demonstrated reduction in ROS levels in the brain, these results demonstrate that the ART12 and ART24 strains of the present technology are useful in methods for the treatment of tauopathies.Example 8: ART12 and ART24 Decrease Chorea in Huntington’s Disease Model

[0192] This example demonstrates that ART 12 and ART24 are useful in methods for treating Huntington’s Disease by reducing or ameliorating chorea.

[0193] Chorea, jerky uncontrolled movements, is an early marker of HD in humans and is a sign of neuromotor impairment. Using the methods described above, the ART24 and ART 12 strains were tested for their capacity to ameliorate or reduce chorea in an HD model. FIG. 13 shows that treatment with either ART 12 or ART24 alone was sufficient to significantly reduce involuntary jerky movements per minute compared to both the mHD group and the Tetrabenazine group, which received an approved human therapeutic for chorea. ART12 / 24 combination treatment also resulted in a significant positive reduction to involuntary jerky movement and even displayed an improved phenotype when compared tothe Tetrabenazine, ART12, and ART24 groups. The results shown in FIG. 13 are reproduced in Table 17 below.Table 17: Average Involuntary Jerk Movements per Minute

[0194] Accordingly, these results demonstrate that both ART12 and ART24 are capable of reducing or ameliorating chorea in a model for HD, and are therefore useful in methods for treating HD.Example 9: ART12 and ART24 Improve Mobility in a Huntington’s Disease Model

[0195] This example will demonstrate that ART 12 and ART24 improve mobility in a model for HD, and are therefore useful in methods for treating HD.

[0196] Using the methods described above, the ART24 and ART12 strains will be tested for their capacity to improve mobility in a model of HD in terms of both time in motion per minute and total swim distance per minute. Decreased mobility due to neuronal degradation and inhibition is associated with HD progression. It is anticipated that the results will show that fish treated with ART12, ART24, or ART12 / 24 spend significantly more time in motion per minute than the mHD group, and will swim significantly more total distance per minute than the mHD group. It is further anticipated that combined treatment with ART12 / 24 will result in a synergistic effect in improving mobility.

[0197] Accordingly, it is anticipated that these results will demonstrate that treatment with ART 12, ART24, or ART 12 / 24 results in improved mobility in a HD model. Therefore, these results will demonstrate that the ART 12 and ART24 strains of the present technology are useful in methods for the treatment of HD.Example 10: ART12 and ART24 Inhibit Neurodegeneration in Huntington’s DiseaseModel

[0198] This example will demonstrate that ART 12 and ART24 are useful in methods for treating Huntington’s Disease by reducing or ameliorating neurodegeneration, and in particular reducing striatal neurodegeneration.

[0199] Neurodegeneration is a sign of HD that worsens as the disease progresses. Striatal neurons are the most vulnerable cell type to HD-mediated degeneration, and striatal neurodegeneration is an early marker for the disease. Using the methods described above, the ART24 and ART 12 strains will be tested for their capacity to prevent, ameliorate, or reduce striatal neurodegeneration in an HD model. It is anticipated that treatment with ART 12, ART24, or ART 12 / 24 will significantly reduce striatal degeneration compared to the mHD group. Additionally, it is anticipated that combined treatment with ART12 / 24 will result in a synergistic effect in reducing striatal degeneration.

[0200] Therefore, it is anticipated that these results will demonstrate that both ART12 and ART24 are capable of reducing or ameliorating neurodegeneration in a model for HD, and are therefore useful in methods for treating HD.Example 11 : ART12 and ART24 Improve ALS Model Operculum and Buccal Movement

[0201] This example demonstrates that the test compounds, ART12 (or ADS012) and ART24 (or ADS024), reduce or ameliorate symptoms of ALS, and are therefore useful in methods for treating ALS.

[0202] Using the methods described above, the ART24 and ART12 strains were tested for their ability to improve operculum movement per min and buccal movement per min in a zebrafish ALS model. More specifically, after the administration of the test compounds, screening was performed on the 9thday post-fertilization (9 dpf) to analyze the behavior and neuro motor responses of the study subjects.

[0203] Operculum movement per minute. Respiratory operculum rate was determined according to a protocol described by Ayoola & Fredrick (Journal of Agriculture and Social Research, 12(1): 1-18 (2012)) and Zaig, et al. (Elife 10:e63407 (Mar. 2021)) with fewmodifications. Briefly, one single larva (9 dpf) at a time (n = 24 / group) was selected at random from each group and transferred into a hollow capillary tube by capillary action along with embryo medium and acclimatized for 3 min. The capillary tube was placed under the stereo microscope and 5X time lapse video was recorded for 3 min with a DSLR model number NIKON D3300 attached to the microscope. To assess the operculum movement, the recorded video was manually analyzed. The number of beats per minute (bpm) was determined by counting the complete cycles of opening and closing of the operculum, which is a thin bony flap covering the gill complex. Each complete cycle was considered as one beat.

[0204] Buccal movement per minute. This assay was performed according to protocol described by Bates, et al. (Dev. Biol. 297(2):374-386 (Sep. 2006)) and Weller, et al. (Integr. Org. Biol. 2(1): pbaa018 (Jun. 2020)) with few modifications. Briefly, for each group 24 larvae at 9 dpf were placed in a single cavity slide containing embryo medium. A 3-minute acclimatization period was provided before initiating the experiment restricting the embryo medium to the body length of the larvae to attain stable swimming condition. After 3 min, one single larva at a time (n = 24 / group) from the cavity slide was transferred to a capillary tube along with embryo medium containing live feed. The larvae were acclimatized for 1 min before performing the observations of buccal movement cycle. The buccal movement cycle refers to the opening of the buccal cavity and the closing of the operculum, followed by suction feeding, allowing fluid to enter the gut. Each complete cycle of these movements was counted as one buccal movement cycle. The capillary tube was placed under the stereo microscope and a DSLR camera model number NIKON D3300 to capture the buccal movement. Time lapse (5X) video was recorded for 3 min for each larva. The buccal movement cycle was calculated manually from the video recordings.

[0205] Kaplan-Meier survival curve. Mortality was recorded daily to understand the survival rate of the study groups over therapeutic intervention.

[0206] Statistics. Statistical analysis of the data was processed by GraphPad Prism 9.0 and expressed as the means ± S.D. Statistical significance was determined by One Way ANOVA along with post-hoc Tukey’s test. Significant differences were assessed at pvalues of p<0.05(**), p<0.001 (***) and p<0.0001(****). P>0.05 (*) was considered nonsignificant.

[0207] Results. The operculum movement per minute amongst the study groups is shown in FIG. 14 and Table 18. WT group larvae had (143 ± 13.91) operculum movements per min. Whereas the ALS model group had a significantly reduced operculum movement (66.42 ± 7.92) in comparison to the WT group (p<0.0001). ALS causes weakness in the muscles involved in breathing and swallowing causing respiratory problems, making breathing more difficult. The mechanism of the clinically used Riluzole has not been fully elucidated, however it stimulates glutamate uptake from synapses and delays the onset of the requirement of mechanical support for breathing in patients with ALS. In this study, the Riluzole treated group had a significant improvement in operculum movements per min (91.67 ± 17.58) (p<0.0001) in comparison to the ALS model which indicates that Riluzole protected the motor function in zebrafish larvae by increasing the operculum movement.

[0208] Furthermore, both the monotherapy and combined therapy involving the test compounds (ADS024 and ADS012) exhibited a substantial enhancement in operculum movement rate, as evidenced by a notable increase in beats per minute compared to the ALS model (p<0.0001). This outcome strongly suggests that the test compounds, whether administered individually or in combination, effectively reinstated the operculum movement frequency per minute, consequently leading to a significant restoration of operculum function in the larvae.Table 18: Operculum movement per minute

[0209] The frequency of buccal movements per minute amongst the study groups is shown in FIG. 15 and Table 19. Larvae in the WT group exhibited a baseline of (135±12.89) buccal movements per minute. Whereas, the ALS model group demonstrated a marked reduction in buccal movement frequency (23.21±7.16) when compared to the WT group (p<0.0001). This reduction in buccal movements is a characteristic outcome of ALS, which induces muscle weakness impacting both breathing and swallowing functions, consequently leading to respiratory challenges and increased breathing difficulty.

[0210] The group treated with Riluzole displayed an improvement in buccal movement frequency (89.67±2.54) (p<0.0001) in contrast to the ALS model group. This observation suggests that Riluzole intervention effectively protected motor function in zebrafish larvae by augmenting buccal movement.

[0211] Furthermore, both the monotherapy and combined therapy involving the test compounds (ADS024 and ADS012) yielded a substantial increase in buccal movement frequency per minute when compared to the ALS model group (p<0.0001). This outcome demonstrates that the test compounds, whether administered individually or in combination, successfully counteracted muscle weakness within the buccal cavity.Table 19: Buccal movement per minute

[0212] As shown in Table 20, no mortality was observed across the study groups.Table 20: Survival percentage

[0213] Summary. This example demonstrates the efficacy of treatment agents, ART12 (ADS012) and ART24 (ADS024), and Riluzole in a zebrafish TDP43' / _ALS model.Screening was performed across operculum movement per minute and buccal movement per minute.

[0214] The results demonstrate that ART 12 treatment and ART24 treatment improve symptoms associated with ALS. Accordingly, these results demonstrate that ART 12 and ART24, either alone or in combination, are useful in methods for treating ALS.EMBODIMENTS

[0215] Reference is made in the following to a number of illustrative embodiments of the subject matter described herein:1. A method for treating, ameliorating, or preventing Multiple Sclerosis comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising one or more bacterial strains selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088).2. The method of embodiment 1, wherein the composition further comprises a preservative.3. The method of embodiment 2, wherein the preservative is a cryoprotectant.4. The method of embodiment 3 wherein the cryoprotectant is selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide.5. The method of embodiment 3, wherein the cryoprotectant is selected from the group consisting of inosine-5 '-monophosphate (IMP), guanosine-5 '-monophosphate (GMP), adenosine-5 '-monophosphate (AMP), uranosine-5 '-monophosphate (UMP), cytidine-5 '-monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, and skim milk.6. The method of embodiment 5, wherein the cryoprotectant comprises trehalose.7. The method of any one of embodiments 1-6, wherein the bacterial strain is lyophilized.8. The method of any one of embodiments 1-7, wherein the bacterial strain is in the form of a spore.The method of any one of embodiments 1-8, wherein the subject is administered the composition at a regular or irregular interval. The method of embodiment 9, wherein the subject is administered the composition daily, weekly, or monthly. The method of embodiment 9, wherein the subject is administered the composition twice a day. The method of any one of embodiments 1-11, wherein the composition is administered orally, sublingually, buccaly, or rectally. The method of any one of embodiments 1-11, wherein the composition is administered enterically. The method of any one of embodiments 1-13, further comprising administering a co-therapeutic to the subject. The method of embodiment 14, wherein the co-therapeutic is administered simultaneously or sequentially with the composition comprising a bacterial strain. The method of embodiment 14 or embodiment 15, wherein the co-therapeutic is an immunomodulatory agent. The method of embodiment 16, wherein the co-therapeutic is fmgolimod. The method of embodiment 14 or embodiment 15, wherein the co-therapeutic is a disease-modifying therapy. The method of any one of embodiments 1-18, wherein the composition comprises ART12. The method of any one of embodiments 1-18, wherein the composition comprises ART24. The method of any one of embodiments 1-20, wherein the composition comprisesART12 and ART24.The method of any one of embodiments 1-21, further comprising evaluating the subject’s symptom severity before composition administration and evaluating the subject’s symptom severity after the composition has been administered at least once. The method of any one of embodiments 1-22, wherein the subject in need thereof is selected for treatment when the subject exhibits a symptom comprising one or more of fatigue, dysesthesia, difficulty walking, numbness, tingling, spasticity, weakness, vision problems, vertigo, dizziness, bladder problems, bowel problems, sexual problems, pain and itching, cognitive function changes, emotional changes, or depression. The method of any one of embodiments 1-22, wherein the subject in need thereof is selected for treatment when the subject exhibits a symptom comprising one or more of elevated levels of antibodies against myelin basic protein (MBP), myelin oligodendrocytic glycoprotein (MOG), Epstein Barr virus, ganglioside and / or neurofilaments, inflammation of the immune system, demyelination of neurons, impaired electrophysiology, elevated kappa free light chain abundance in cerebrospinal fluids, or lesions on the brain or spinal cord. The method of embodiment 23, wherein the subject exhibits improved or reduced symptoms after administration of the composition. The method of embodiment 24, wherein the subject exhibits improved or reduced symptoms after administration of the composition. The method of any one of embodiments 1-26, wherein the subject has primary progressive Multiple Sclerosis, relapsing remitting Multiple Sclerosis, secondary progressive Multiple Sclerosis, or clinically isolated syndrome. The method of any one of embodiments 1-21, wherein the subject is asymptomatic and is at elevated risk of Multiple Sclerosis. The method of embodiment 28, wherein the subject exhibits a delay in onset of Multiple Sclerosis after administration of the composition.The method of any one of embodiments 1-29, wherein the composition further comprises a pharmaceutically appropriate excipient. A kit for use in treating Multiple Sclerosis comprising(a) a composition comprising a bacterial strain selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088); and(b) a package insert with instructions for treating Multiple Sclerosis in a subject in need thereof. The kit of embodiment 31, wherein the instructions indicate that the bacterial strain is administered to the subject twice daily. The kit of embodiment 31 or embodiment 32, wherein the insert further instructs that the bacterial strain be administered orally. The kit of any one of embodiments 31-33, wherein the insert further instructs that the subject’s symptoms are tracked during the period of treatment. The kit of any one of embodiments 31-34, wherein the concentration of the bacterial strain is about IxlO8CFU / ml bacteria to about IxlO12CFU / ml bacteria. The kit of any one of embodiments 31-35, wherein the insert further instructs that the subject be administered about IxlO9CFU to about IxlO12CFU of the bacterial strain per day. The kit of any one of embodiments 31-36, wherein the composition comprising the bacterial strain is formulated for oral administration. The kit of any one of embodiments 31-37, further comprising a co-therapeutic. A method for treating or preventing Autism Spectrum Disorder comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the bacterial strain ART24 (NCIMB Accession No. 43088).The method of embodiment 39, wherein the composition further comprises a preservative. The method of embodiment 40, wherein the preservative is a cryoprotectant. The method of embodiment 41 wherein the cryoprotectant is selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide. The method of embodiment 41, wherein the cryoprotectant is selected from the group consisting of inosine-5 '-monophosphate (IMP), guanosine-5 '-monophosphate (GMP), adenosine-5 '-monophosphate (AMP), uranosine-5 '-monophosphate (UMP), cytidine-5 '-monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, and skim milk. The method of embodiment 43, wherein the cryoprotectant comprises trehalose. The method of any one of embodiments 39-44, wherein the bacterial strain is lyophilized. The method of any one of embodiments 39-45, wherein the bacterial strain is in the form of a spore. The method of any one of embodiments 39-46, wherein the subject is administered the composition at a regular or irregular interval. The method of embodiment 47, wherein the subject is administered the composition daily, weekly, or monthly. The method of embodiment 47, wherein the subject is administered the composition twice a day. The method of any one of embodiments 39-49, wherein the composition is administered orally, sublingually, buccaly, or rectally.The method of any one of embodiments 39-49, wherein the composition is administered enterically. The method of any one of embodiments 39-51, further comprising administering a co-therapeutic to the subject. The method of embodiment 52, wherein the co-therapeutic is administered simultaneously or sequentially with the composition comprising a bacterial strain. The method of embodiment 52 or embodiment 53, wherein the co-therapeutic is a course of therapy. The method of embodiment 54, wherein the course of therapy is selected from the group consisting of talk therapy, discrete trial training, pivotal response training, speech and language therapy, occupational therapy, sensory integration therapy, physical therapy, social -relational training, and cognitive-behavior therapy. The method of embodiment 52 or embodiment 53, wherein the co-therapeutic treats co-occurring symptoms of autism spectrum disorder. The method of embodiment 55, wherein the co-occurring symptoms comprise irritability, high energy levels, inability to focus, self-harm, anxiety, depression, seizures, sleep problems, gastrointestinal pathologies, or any combination thereof. The method of embodiment 55, wherein the co-therapeutic comprises risperidone, aripiprazole, or a combination thereof. The method of any one of embodiments 39-57, further comprising evaluating the subject’s symptom severity before composition administration and evaluating the subject’s symptom severity after the composition has been administered at least once. The method of any one of embodiments 39-58, wherein the subject in need thereof is selected for treatment when the subject exhibits a symptom comprising impaired social communication and interaction skills, restricted or repetitive behaviors or interests, delayed development of language skills, delayed development ofmovement skills, delayed development of cognitive or learning skills, hyperactive, impulsive, or inattentive behavior, epilepsy, seizures, gastrointestinal diseases or disorders, anxiety, excessive fear or fearlessness, or any combination thereof. The method of embodiment 59, wherein the impaired social communication and interaction skills comprises a lack of eye contact, lack of responsiveness to name, lack of facial expressions, failure to interact with others, failure to make hand gestures, failure to react to the emotions of other, or any combination thereof. The method of any one of embodiments 39-60, wherein the subject in need thereof is diagnosed as having an Autism Spectrum Disorder based on a diagnostic system. The method of embodiment 61, wherein the diagnostic system is selected from the group consisting of Childhood Autism Rating Scale (CARS), Childhood Autism Rating Scale 2 - Standard Form (CARS2-ST), Childhood Autism Rating Scale 2 - High Functioning (CARS2-ST), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Vineland Adaptive Behavior Scale II (VABS-II), Autism Diagnosis Interview (ADI-R), Autism Diagnostic Observation Schedule - Generic (ADOS-G), Gilliam Autism Rating Scale - Second Edition (GARS-2), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The method of any one of embodiments 39-62, wherein the subject exhibits improved or reduced symptoms after administration of the composition. The method of any one of embodiments 39-63, wherein the subject has autistic disorder, pervasive developmental disorder not otherwise specified, or Asperger syndrome. The method of any one of embodiments 39-57, wherein the subject is asymptomatic and is at elevated risk of Autism Spectrum Disorder. The method of embodiment 65, wherein the subject exhibits a delay in onset of Autism Spectrum Disorder symptoms after administration of the composition.The method of any one of embodiments 39-66, wherein the composition further comprises a pharmaceutically appropriate excipient. The method of any one of embodiments 39-67, wherein the method further treats or prevents social anxiety in the subject in need thereof. A method for increasing social behavior, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the bacterial strain ART24 (NCIMB Accession No. 43088). A method for treating social anxiety, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising the bacterial strain ART24 (NCIMB Accession No. 43088). The method of embodiments 69 or 70, wherein the subject has been diagnosed with or is suspected of having Autism Spectrum Disorder or social anxiety. The method of any one of embodiments 69-71, wherein the subject exhibits improved sociability after administration of the composition. A kit for use in treating Autism Spectrum Disorder, social anxiety, or a combination thereof comprising(a) a composition comprising the bacterial strain ART24 (NCIMB Accession No. 43088); and(b) a package insert with instructions for treating Autism Spectrum Disorder, social anxiety, or a combination thereof in a subject in need thereof. The kit of embodiment 73, wherein the instructions indicate that the bacterial strain is administered to the subject twice daily. The kit embodiment 73 or embodiment 74, wherein the insert further instructs that the bacterial strain be administered orally. The kit of any one of embodiments 73-75, wherein the insert further instructs that the subject’s symptoms are tracked during the period of treatment.The kit of any one of embodiments 73-76, wherein the concentration of the bacterial strain is about IxlO8CFU / ml bacteria to about IxlO12CFU / ml bacteria. The kit of any one of embodiments 73-77, wherein the insert further instructs that the subject be administered about IxlO9CFU to about IxlO12CFU of the bacterial strain per day. The kit of any one of embodiments 73-78, wherein the composition comprising the bacterial strain is formulated for oral administration. The kit of any one of embodiment 73-79, wherein the composition comprising the bacterial strain further comprises a co-therapeutic. A method for treating or preventing a tauopathy in a subj ect in need thereof comprising administering to the subject a therapeutically effective amount of a composition comprising one or more bacterial strains selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088). The method of embodiment 81, wherein the composition further comprises a preservative. The method of embodiment 82, wherein the preservative is a cryoprotectant. The method of embodiment 83, wherein the cryoprotectant is selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide. The method of embodiment 83, wherein the cryoprotectant is selected from the group consisting of inosine-5 '-monophosphate (IMP), guanosine-5 '-monophosphate (GMP), adenosine-5 '-monophosphate (AMP), uranosine-5 '-monophosphate (UMP), cytidine-5 '-monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, and skim milk. The method of embodiment 85, wherein the cryoprotectant comprises trehalose.The method of any one of embodiments 81-86, wherein the bacterial strain is lyophilized. The method of any one of embodiments 81-87, wherein the bacterial strain is in the form of a spore. The method of any one of embodiments 81-88, wherein the subject is administered the composition at a regular or irregular interval. The method of embodiment 89, wherein the subject is administered the composition daily, weekly, or monthly. The method of embodiment 89, wherein the subject is administered the composition once a day. The method of any one of embodiments 81-91, wherein the composition is administered orally, sublingually, buccaly, or rectally. The method of any one of embodiments 81-91, wherein the composition is administered enterically. The method of any one of embodiments 81-93, further comprising administering a co-therapeutic to the subject. The method of embodiment 94, wherein the co-therapeutic is administered simultaneously or sequentially with the composition. The method of embodiment 94 or embodiment 95, wherein the co-therapeutic treats Tau aggregation. The method of embodiment 96, wherein the co-therapeutic is selected from a group consisting of anti-Tau antibodies, vaccines inducing immunity against tau, tau- disaggregation agents, anti-tau-expression agents, anti-amyloid plaque agents, antiamyloid antibodies, modulators of Tau phosphorylation, modulators of Tau acylation, histone deacetylase inhibitors, modulators of Tau glycosylation, inhibitors of Tau glycosylation, modulators of Tau truncation, proteasome stimulators, USP14inhibitors, phosphodiesterase inhibitors, autophagy activators, chaperone modulators, co-chaperone modulators, and Tau oriented multi-target directed ligands. The method of embodiment 94 or embodiment 95, wherein the co-therapeutic treats a symptom associated with the tauopathy. The method of embodiment 98, wherein the symptom associated with the tauopathy comprises one or more of disinhibition, apathy, loss of empathy, stereotypic behaviors, hyperorality, memory loss, difficulty communicating and reasoning, confusion, loss of coordination, depression, anxiety, paranoia, agitation, hallucinations, postural instability, vertical supranuclear ophthalmoplegia, asymmetrical limb apraxia, cortical function deficits, asymmetric onset of tremor, bradykinesia, rigidity, cerebellar ataxia, difficulty speaking, anomia, impaired comprehension, phonemic paraphasia, motor speech disorder, visuospatial disorientation, and impaired executive abilities. The method of any one of embodiments 81-99, wherein the composition comprises ART12. The method of any one of embodiments 81-99, wherein the composition comprises ART24. The method of any one of embodiments 81-101, wherein the composition comprises ART12 and ART24. The method of any one of embodiments 81-102, further comprising evaluating the subject’s symptom severity before composition administration and evaluating the subject’s symptom severity after the composition has been administered at least once. The method of any one of embodiments 81-103, wherein the subject is selected for treatment when the subject exhibits a symptom comprising one or more of disinhibition, apathy, loss of empathy, stereotypic behaviors, hyperorality, memory loss, difficulty communicating and reasoning, confusion, loss of coordination,depression, anxiety, paranoia, agitation, hallucinations, postural instability, vertical supranuclear ophthalmoplegia, asymmetrical limb apraxia, cortical function deficits, asymmetric onset of tremor, bradykinesia, rigidity, cerebellar ataxia, difficulty speaking, anomia, impaired comprehension, phonemic paraphasia, motor speech disorder, visuospatial disorientation, or impaired executive abilities. The method of any one of embodiments 81-104, wherein the genome of the subject comprises a mutated microtubule associated protein Tau (MAPT) gene. The method of embodiment 105, wherein the mutated MAPT gene comprises one or more mutations selected from the group consisting of: R5H, R5L, G55R, A152T, K257T, I260V, L266V, G272V, G273R, N279K, K280del, L284L, L284R, S285R, C291R, N296del, N296D, N296H, N296N, P301L, P301S, P301T, G303V, S305I, S305N, S305S, L315L, L315R, K317M, K317N, S320F, S320Y, P332S, G335A, G335S, G335V, Q336H, Q336R, V337M, E342V, S352L, S356T, V363I, P364S, G366R, K369I, E372G, G389R, P397S, R406W, R406G, and N410H. The method of any one of embodiments 81-106, wherein the subject exhibits improved or reduced symptoms after administration of the composition. The method of any one of embodiments 81-107, wherein the subject is diagnosed with a tauopathy. The method of any one of embodiments 81-102, wherein the subject is asymptomatic and is at elevated risk of a tauopathy. The method of embodiment 109, wherein the subject exhibits a delay in onset of the tauopathy after administration of the composition. The method of any one of embodiments 81-110, wherein the composition further comprises a pharmaceutically acceptable excipient. The method of any one of embodiments 81-111, wherein the tauopathy comprises a 3R, 4R, or 3R+4R tauopathy.The method of any one of embodiments 81-112, wherein the tauopathy is associated with one or more of Alzheimer's disease, amyotrophic lateral sclerosis, Parkinsonism-dementia complex, anti -IgLON5 -related tauopathy, Caribbean Parkinsonism, chronic traumatic encephalopathy, diffuse neurofibrillary tangles with calcification, progressive supranuclear palsy, Down syndrome, Familial British dementia, Familial Danish dementia, Niemann-Pick disease type C, non-Guamanian motor neuron disease with neurofibrillary tangles, postencephalitic Parkinsonism, primary age-related tauopathy, progressive ataxia, palatal tremor, neurofibrillary dementia, familial frontotemporal dementia, Parkinsonism, Pick's disease, argyrophilic grain disease, corticobasal degeneration, Guadeloupean Parkinsonism, globular glial tauopathy, Huntington's Disease, SLC9a-related Parkinsonism, Tau astrogliopathy, and aging-related Tau astrogliopathy. A kit for use in treating a tauopathy comprising:(a) a composition comprising a bacterial strain selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088); and(b) a package insert with instructions for treating a tauopathy in a subject in need thereof. The kit of embodiment 114, wherein the instructions indicate that the bacterial strain is administered to the subject at least once daily. The kit embodiment 114 or embodiment 115, wherein the insert further instructs that the bacterial strain be administered orally. The kit of any one of embodiments 114-116, wherein the insert further instructs that the subject’s symptoms are tracked during the period of treatment. The kit of any one of embodiments 114-117, wherein the concentration of the bacterial strain is about IxlO8CFU / ml bacteria to about IxlO12CFU / ml bacteria.The kit of any one of embodiments 114-118, wherein the insert further instructs that the subject be administered about IxlO9CFU to about IxlO12CFU of the bacterial strain per day. The kit of any one of embodiments 114-119, wherein the composition comprising the bacterial strain is formulated for oral administration. The kit of any one of embodiments 114-120, further comprising a co-therapeutic. A method for treating or preventing Huntington’s Disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising one or more bacterial strains selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088). The method of embodiment 122, wherein the composition further comprises a preservative. The method of embodiment 123, wherein the preservative is a cryoprotectant. The method of embodiment 124, wherein the cryoprotectant is selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide. The method of embodiment 3, wherein the cryoprotectant is selected from the group consisting of inosine-5 '-monophosphate (IMP), guanosine-5 '-monophosphate (GMP), adenosine-5 '-monophosphate (AMP), uranosine-5 '-monophosphate (UMP), cytidine-5 '-monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, and skim milk. The method of embodiment 126, wherein the cryoprotectant comprises trehalose. The method of any one of embodiments 122-127, wherein the bacterial strain is lyophilized.The method of any one of embodiments 122-128, wherein the bacterial strain is in the form of a spore. The method of any one of embodiments 122-129, wherein the subject is administered the composition at a regular or irregular interval. The method of embodiment 130, wherein the subject is administered the composition daily, weekly, or monthly. The method of embodiment 130, wherein the subject is administered the composition once a day. The method of any one of embodiments 122-132, wherein the composition is administered orally, sublingually, buccaly, or rectally. The method of any one of embodiments 122-132, wherein the composition is administered enterically. The method of any one of embodiments 122-134, further comprising administering a co-therapeutic to the subject. The method of embodiment 135, wherein the co-therapeutic is administered simultaneously or sequentially with the composition comprising a bacterial strain. The method of embodiment 135 or embodiment 136, wherein the co-therapeutic treats a symptom associated with Huntington’s Disease. The method of embodiment 137, wherein the co-therapeutic is selected from a group consisting of olanzapine, pimozide, risperidone, fluphenazine, tetrabenazine, deuterabenazine, amantadine, levetiracetam, clonazepam, haloperidol, aripiprazole, quetiapine, citalopram, escitalopram, fluoxetine, sertraline, divalproex, carbamazepine, lamotrigine, antipsychotics, antidepressants, anticonvulsants, moodstabilizing drugs, and anti-anxiety agents. The method of embodiment 137, wherein the symptom associated with Huntington’s Disease comprises one or more of uncontrolled movements, chorea, akinesia,bradykinesia, hypokinesia, dysarthria, dysphagia, dystonia, tremors, slurred speech, difficulty swallowing, eating, speaking or walking, weight loss, lung infections, insomnia, fatigue, seizures, cognitive decline, dementia, psychosis, hallucinations, delusions, violent outbursts, depression, or anxiety. The method of any one of embodiments 122-139, wherein the composition comprises ART 12. The method of any one of embodiments 122-139, wherein the composition comprises ART24. The method of any one of embodiments 122-141, wherein the composition comprises ART 12 and ART24. The method of any one of embodiments 122-142, further comprising evaluating the subject’s symptom severity before composition administration and evaluating the subject’s symptom severity after the composition has been administered at least once. The method of any one of embodiments 122-143, wherein the subject is selected for treatment when the subject exhibits a symptom comprising one or more of uncontrolled movements, chorea, akinesia, bradykinesia, hypokinesia, dysarthria, dysphagia, dystonia, tremors, slurred speech, difficulty swallowing, eating, speaking or walking, weight loss, lung infections, insomnia, fatigue, seizures, cognitive decline, dementia, psychosis, hallucinations, delusions, violent outbursts, depression, or anxiety. The method of any one of embodiments 122-144, wherein the genome of the subject comprises a mutated Huntingtin gene. The method of embodiment 145, wherein the mutated Huntingtin gene comprises at least 36 consecutive CAG repeats. The method of any one of embodiments 122-146, wherein the subject exhibits improved or reduced symptoms after administration of the composition.The method of any one of embodiments 122-147, wherein the subject is clinically diagnosed with Huntington’s Disease. The method of any one of embodiments 122-142, wherein the subject is asymptomatic and is at elevated risk of Huntington’s Disease. The method of embodiment 149, wherein the subject exhibits a delay in onset of Huntington’s Disease after administration of the composition. The method of any one of embodiments 122-150, wherein the composition further comprises a pharmaceutically acceptable excipient. A kit for use in treating Huntington’s Disease comprising:(a) a composition comprising a bacterial strain selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088); and(b) a package insert with instructions for treating Huntington’ s Disease in a subject in need thereof. The kit of embodiment 152, wherein the instructions indicate that the bacterial strain is administered to the subject at least once daily. The kit embodiment 152 or embodiment 153, wherein the insert further instructs that the bacterial strain be administered orally. The kit of any one of embodiments 152-154, wherein the insert further instructs that the subject’s symptoms are tracked during the period of treatment. The kit of any one of embodiments 152-155, wherein the concentration of the bacterial strain is about IxlO8CFU / ml bacteria to about IxlO12CFU / ml bacteria. The kit of any one of embodiments 152-156, wherein the insert further instructs that the subject be administered about IxlO9CFU to about IxlO12CFU of the bacterial strain per day.The kit of any one of embodiments 152-157, wherein the composition comprising the bacterial strain is formulated for oral administration. The kit of any one of embodiments 152-158, further comprising a co-therapeutic. A method for treating or preventing amyotrophic lateral sclerosis (ALS) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising one or more bacterial strains selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088). The method of embodiment 160, wherein the composition further comprises a preservative. The method of embodiment 161, wherein the preservative is a cryoprotectant. The method of embodiment 162 wherein the cryoprotectant is selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide. The method of embodiment 162, wherein the cryoprotectant is selected from the group consisting of inosine-5 '-monophosphate (IMP), guanosine-5 '-monophosphate (GMP), adenosine-5 '-monophosphate (AMP), uranosine-5 '-monophosphate (UMP), cytidine-5 '-monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, and skim milk. The method of embodiment 164, wherein the cryoprotectant comprises trehalose. The method of any one of embodiments 160-165, wherein the bacterial strain is lyophilized. The method of any one of embodiments 160-166, wherein the bacterial strain is in the form of a spore.The method of any one of embodiments 160-167, wherein the subject has been diagnosed as having ALS. The method of any one of embodiments 160-168, wherein the ALS is familial. The method of embodiment 169, wherein the familial ALS is caused by a mutation in the TARDBP gene. The method of any one of embodiments 160-170, wherein the subject is administered the composition at a regular or irregular interval. The method of embodiment 171, wherein the subject is administered the composition daily, weekly, or monthly. The method of embodiment 171, wherein the subject is administered the composition twice a day. The method of any one of embodiments 160-173, wherein the composition is administered orally, sublingually, buccaly, or rectally. The method of any one of embodiments 160-173, wherein the composition is administered enterically. The method of any one of embodiments 160-175, further comprising administering a co-therapeutic to the subject. The method of embodiment 176, wherein the co-therapeutic is administered simultaneously or sequentially with the composition comprising the one or more bacterial strains. The method of embodiment 176 or embodiment 177, wherein the co-therapeutic is selected from the group consisting of: riluzole (Rilutek®, Tiglutik™, Exservan™), tofersen (QALSODY™), sodium phenylbutyrate and taurursodiol (RELYVRIO™), dextromethorphan / quinidine (Nuedexta®), edaravone (Radicava®), mecasermin, baclofen (Lioresal®), diazepam (Valium®), dantrolene (Dantrium®), nonsteroidal anti-inflammatory agents, anti convulsive medications, and any combination thereof.The method of any one of embodiments 160-178, wherein the treating or preventing comprises the treatment or prevention of one or more signs of symptoms of ALS comprising one or more of muscle weakness, muscle wasting, muscle fasciculations, muscle spasticity, slowness of movement, poor balance, incoordination, alterations in vocal quality, dysarthria, dysphagia, incomplete eye closure, drooling, pseudobulbar affect, premature death, increased brain translocator protein- 18 kDa expression, respiratory muscle weakness, dyspnea with mild exertion, supine dyspnea, respiratory insufficiency, and / or elevated plasma or cerebrospinal fluid levels of neurofilament light chain. The method of any one of embodiments 160-179, wherein the subject is a mammal. The method of embodiment 180, wherein the subject is a human. The method of any one of embodiments 160-181, wherein the composition comprises ART 12. The method of any one of embodiments 160-181, wherein the composition comprises ART24. The method of any one of embodiments 160-183, wherein the composition comprises ART 12 and ART24. The method of any one of embodiments 160-184, further comprising evaluating the subject’s symptom severity before composition administration and evaluating the subject’s symptom severity after the composition has been administered at least once. The method of any one of embodiments 160-185, wherein the subject in need thereof is selected for treatment when the subject exhibits a symptom comprising one or more of muscle weakness, muscle wasting, muscle fasciculations, muscle spasticity, slowness of movement, poor balance, incoordination, alterations in vocal quality, dysarthria, dysphagia, incomplete eye closure, drooling, pseudobulbar affect, premature death, increased brain translocator protein- 18 kDa expression, respiratory muscle weakness, dyspnea with mild exertion, supine dyspnea,respiratory insufficiency, and / or elevated plasma or cerebrospinal fluid levels of neurofilament light chain. The method of embodiment 186, wherein the subject exhibits improved or reduced symptoms after administration of the composition. The method of any one of embodiments 160-187, wherein the subject is asymptomatic and is at elevated risk of ALS. The method of embodiment 188, wherein the subject exhibits a delay in onset of ALS after administration of the composition. The method of any one of embodiments 160-189, wherein the composition further comprises a pharmaceutically appropriate excipient. A kit for use in treating ALS comprising:(a) a composition comprising a bacterial strain selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088); and(b) a package insert with instructions for treating ALS in a subject in need thereof. The kit of embodiment 191, wherein the instructions indicate that the bacterial strain is administered to the subject twice daily. The kit of embodiment 191 or embodiment 192, wherein the insert further instructs that the bacterial strain be administered orally. The kit of any one of embodiments 191-193, wherein the insert further instructs that the subject’s symptoms are tracked during the period of treatment. The kit of any one of embodiments 191-194, wherein the concentration of the bacterial strain is about IxlO8CFU / ml bacteria to about IxlO14CFU / ml bacteria.The kit of any one of embodiments 191-195, wherein the insert further instructs that the subject be administered about IxlO9CFU to about IxlO14CFU of the bacterial strain per day. The kit of any one of embodiments 191-196, wherein the composition comprising the bacterial strain is formulated for oral administration. The kit of any one of embodiments 191-197, further comprising a co-therapeutic.BIOLOGICAL DEPOSITS

[0216] The Applicant requests that a sample of the deposited microorganisms should be made available only to an expert approved by the Applicant.

[0217] Bacillus amyloliquefaciens strain ART 12 deposited with the National Collection of Industrial Food and Marine Bacteria (NCIMB Ltd.) (International Depositary Authority), Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland, on 21 June 2018, under NCIMB Accession Number 43087.

[0218] Bacillus amyloliquefaciens strain ART24 deposited with the National Collection of Industrial Food and Marine Bacteria (NCIMB Ltd.) (International Depositary Authority), Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, Scotland, on 21 June 2018, under NCIMB Accession Number 43088.

[0219] The deposits were made according to the Budapest treaty on the international recognition of the deposit of microorganisms for the purposes of patent procedure.EQUIVALENTS

[0220] The present technology is not to be limited in terms of the particular embodiments described in this application, which are intended as single illustrations of individual aspects of the present technology. Many modifications and variations of this present technology can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the present technology, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. The present technology is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is to be understood that this present technology is not limited to particular methods, reagents, compounds compositions or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0221] Each and every publication and patent mentioned in the above specification is herein incorporated by reference in its entirety for all purposes. Various modifications and variations of the described methods and system of the present technology will be apparent to those skilled in the art without departing from the scope and spirit of the present technology. Although the present technology has been described in connection with specific embodiments, the present technology as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the present technology which are obvious to those skilled in the art and in fields related thereto are intended to be within the scope of the following claims.

Claims

CLAIMSWhat is claimed is:

1. A method for treating, ameliorating, or preventing a disease selected from the group consisting of: multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, and amyotrophic lateral sclerosis, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising one or more bacterial strains selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088).

2. The method of claim 1, wherein the composition further comprises a preservative.

3. The method of claim 2, wherein the preservative is a cryoprotectant.

4. The method of claim 3 wherein the cryoprotectant is selected from the group consisting of a nucleotide, a disaccharide, a polyol, and a polysaccharide.

5. The method of claim 3, wherein the cryoprotectant is selected from the group consisting of inosine-5 '-monophosphate (IMP), guanosine-5 '-monophosphate (GMP), adenosine-5 '-monophosphate (AMP), uranosine-5 '-monophosphate (UMP), cytidine-5 '-monophosphate (CMP), adenine, guanine, uracil, cytosine, guanosine, uridine, cytidine, hypoxanthine, xanthine, orotidine, thymidine, inosine, trehalose, maltose, lactose, sucrose, sorbitol, mannitol, dextrin, inulin, sodium ascorbate, glutathione, and skim milk.

6. The method of claim 5, wherein the cryoprotectant comprises trehalose.

7. The method of any one of claims 1-6, wherein the bacterial strain is lyophilized.

8. The method of any one of claims 1-7, wherein the bacterial strain is in the form of a spore.

9. The method of any one of claims 1-8, wherein the subject is administered the composition at a regular or irregular interval.

10. The method of claim 9, wherein the subject is administered the composition daily, weekly, or monthly.

11. The method of claim 9, wherein the subject is administered the composition twice a day.

12. The method of any one of claims 1-11, wherein the composition is administered orally, sublingually, buccaly, or rectally.

13. The method of any one of claims 1-11, wherein the composition is administered enterically.

14. The method of any one of claims 1-13, further comprising administering a co- therapeutic to the subject.

15. The method of claim 14, wherein the co-therapeutic is administered simultaneously or sequentially with the composition comprising a bacterial strain.

16. The method of any one of claims 1-15, wherein the composition comprises ART12.

17. The method of any one of claims 1-16, wherein the composition comprises ART24.

18. The method of any one of claims 1-17, wherein the composition comprises ART12 and ART24.

19. The method of any one of claims 1-18, further comprising evaluating the subject’s symptom severity before composition administration and evaluating the subject’s symptom severity after the composition has been administered at least once.

20. The method of claim 19, wherein the subject exhibits improved or reduced symptoms after administration of the composition.

21. The method of any one of claims 1-20, wherein the subject is asymptomatic and is at elevated risk of multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, or amyotrophic lateral sclerosis.

22. The method of claim 28, wherein the subject exhibits a delay in onset multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, and amyotrophic lateral sclerosis after administration of the composition.

23. The method of any one of claims 1-22, wherein the composition further comprises a pharmaceutically appropriate excipient.

24. The method of any one of claims 1-23, wherein the disease is multiple sclerosis.

25. The method of any one of claims 1-23, wherein the disease is autism spectrum disorder and / or social anxiety.

26. The method of any one of claims 1-23, wherein the disease is a tauopathy.

27. The method of any one of claims 1-23, wherein the disease is Huntington’s Disease.

28. The method of any one of claims 1-23, wherein the disease is amyotrophic lateral sclerosis.

29. A kit for use in treating a disease selected from the group consisting of: multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, and amyotrophic lateral sclerosis comprising:(a) a composition comprising a bacterial strain selected from the group consisting of ART12 (NCIMB Accession No. 43087) and ART24 (NCIMB Accession No. 43088); and(b) a package insert with instructions for treating multiple sclerosis, autism spectrum disorder and / or social anxiety, tauopathies, Huntington’s Disease, or amyotrophic lateral sclerosis in a subject in need thereof.

30. The kit of claim 29, wherein the instructions indicate that the bacterial strain is administered to the subject twice daily.

31. The kit of claim 29 or claim 30, wherein the insert further instructs that the bacterial strain be administered orally.

32. The kit of any one of claims 29-31, wherein the insert further instructs that the subject’s symptoms are tracked during the period of treatment.

33. The kit of any one of claims 29-32, wherein the concentration of the bacterial strain is about IxlO8CFU / ml bacteria to about IxlO14CFU / ml bacteria.

34. The kit of any one of claims 29-33, wherein the insert further instructs that the subject be administered about IxlO9CFU to about IxlO14CFU of the bacterial strain per day.

35. The kit of any one of claims 29-34, wherein the composition comprising the bacterial strain is formulated for oral administration.

36. The kit of any one of claims 29-35, further comprising a co-therapeutic.

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