Novel co-cultured microbial consortia and methods

Abstract

Described herein are compositions comprising a microbial consortium for treating or preventing medical disorders and pathologies through microbiome modulation, including medical disorders associated with a dysbiosis or a loss of gut microbial function. Embodiments described herein also relate to methods of treating medical disorders and pathologies by administering the composition to a patient in need thereof and methods of producing compositions of the present disclosure.

Description

Novel Co-cultured Microbial Consortia and MethodsField

[0001] Embodiments provided herein relate to compositions comprising a microbial consortium for treating or preventing medical disorders and pathologies through microbiome modulation, including medical disorders associated with a dysbiosis or a loss of gut microbial function. Embodiments described herein also relate to methods of treating medical disorders and pathologies by administering the composition to a patient in need thereof and methods of producing compositions of the present disclosure.Background

[0002] The following discussion of the background art is intended to facilitate an understanding of the present disclosure only. The discussion is not an acknowledgement or admission that any of the material referred to is or was part of the common general knowledge as at the priority date of the application.

[0003] The human intestinal microbiota consists of trillions of microorganisms including at least 100 prevalent and at least 1000 less common bacterial species, comprising over 100- fold more genes than those present in the human genome. The intestinal microbiota is composed predominantly of bacteria, yet also contains fungi, archaea, protozoa, and viruses. The microbiota performs vital functions essential to health maintenance, including food processing, digestion of complex indigestible polysaccharides and synthesis of vitamins, and it secretes bioactive metabolites with diverse functions, ranging from inhibition of pathogens, metabolism of toxic compounds, to modulation of host metabolism.

[0004] There is a need in the art for effective treatments of treating medical disorders and pathologies through microbiome modulation, particularly for disorders associated with a dysbiosis or a loss of gut microbial function.Summary

[0005] The present inventors have surprisingly identified culture expanded communities of microbial species and methods of producing same at scale. In certain examples, the identified culture expanded communities comprise selected core community species and keystone species. Accordingly, in a first embodiment, the present disclosure relates to a composition comprising a culture expanded community of microbial species, comprising a keystone microbial species selected from Table 13 and a plurality of core community microbial species selected from Table 14, wherein the keystone microbial species and the core community microbial species are culture expanded in co-culture under culture conditions.

[0006] In an example, the composition of the disclosure may be a co-culture, wherein the co-culture is defined by its core community and keystone species. For example, the co-culturemay comprise a keystone microbial species selected from Table 13 and a plurality of core community microbial species selected from Table 14. In another example, the composition is purified or partially purified from a co-culture disclosed herein.

[0007] In an example, the composition is formulated as a tablet, capsule or powder. Accordingly, in an example, the present disclosure encompasses a tablet comprising a culture expanded community of microbial species disclosed herein. In another example, the present disclosure encompasses a capsule comprising a culture expanded community of microbial species disclosed herein. In an example, the tablet or capsule may comprise an enteric coating. In an example, the composition is subject to double encapsulation. In another example, the present disclosure encompasses a power comprising a culture expanded community of microbial species disclosed herein. Accordingly, in an example, the compositions of the present disclosure may be lyophilized. In an example, the lyophilized composition may comprise inulin and maltodextrin.

[0008] The present inventors have surprisingly identified a selection of microbial species that can be culture expanded to provide a beneficial composition, for example, therapeutically beneficial composition(s). Such populations, in certain examples, may be used to inoculate a suitable culture medium and facilitate culture expansion. In an example, the population is a starting population. In another example, the population has been culture expanded several times, for example, in two or more bioreactors before being used to inoculate a suitable culture medium. Accordingly, in another example, the present disclosure relates to an inoculum for microbial culture, the inoculum comprising a composition of the disclosure. For example, the inoculum may comprise a keystone microbial species selected from Table 13 and a plurality of core community microbial species selected from Table 14. In another example, the inoculum comprises a selection of microbial species from Table 31 and / or Table 33. For example, the inoculum may comprise a selection of microbial species from Table 31. In another example, the inoculum may comprise a selection of microbial strains from Table 31. In another example, the inoculum may comprise a selection of microbial species from Table 33. In another example, the inoculum may comprise a selection of microbial strains from Table 33. In another example, the inoculum comprises the microbial species from Table 31. In another example, the inoculum comprises the microbial strains from Table 31. In another example, the inoculum comprises the microbial species from Table 33. In another example, the inoculum comprises the microbial strains from Table 33.

[0009] In another example, the inoculum comprises a selection of microbial species from Table 34 and / or Table 35. For example, the inoculum may comprise a selection of microbial species from Table 34. In another example, the inoculum may comprise a selection of microbial strains from Table 34. In another example, the inoculum may comprise a selection of microbial species from Table 35. In another example, the inoculum may comprise a selection of microbial strains from Table 35. In another example, the inoculum comprises themicrobial species from Table 34. In another example, the inoculum comprises the microbial strains from Table 34. In another example, the inoculum comprises the microbial species from Table 35. In another example, the inoculum comprises the microbial strains from Table 35. In an example, the inoculum is culture expanded. In an example, the inoculum is provided in a growth medium.

[0010] In several alternative embodiments, the present disclosure relates to a formulation comprising multiple core community microbial strains as well as multiple keystone microbial strains that are provided to, for example, restore gut microbiome ecology. In some embodiments, the core community and keystone strains are co-cultured together to provide a improved consortium with diverse species. When administered to a subject, according to one embodiment, the consortium is capable of providing a beneficially stable microbial ecosystem because the various strains have already been co-cultured together prior to administration.

[0011] In some embodiments, a diverse range of gene families, as described herein, provides the ability to deliver therapies that have broad functional capability as well as highly targeted disease specific function. Oral formulations are provided in several embodiments, which in turn can eliminate the reliance on stool donors and enables production of microbial therapies at scale, to large markets.

[0012] In an example, compositions of the disclosure are generated by co-culturing core community microbial species and the keystone microbial species in a bioreactor.

[0013] In another example, the tablet, capsule or powder compositions described herein are characterized by capability to metabolize hydrogen sulfide in the gastrointestinal tract of a subject post administration.

[0014] In another example, compositions of the disclosure comprise maltodextrin. In another example, compositions of the disclosure comprise inulin. In another example, compositions of the disclosure comprise inulin and maltodextrin. In an example, compositions of the disclosure comprise <12% inulin and <12% maltodextrin. In an example, compositions of the disclosure comprise <10% inulin and <10% maltodextrin. In an example, compositions of the disclosure comprise <7% inulin and <7% maltodextrin. In certain examples, the compositions comprising a specified % of inulin / maltodextrin are lyophilized.

[0015] In other examples, compositions of the disclosure further comprise a prebiotic. In an example, oral formulations of the disclosure, such as tablets or capsules, may comprise an enteric coating. In other examples, powders of the disclosure may be encapsulated in an enteric coating.

[0016] In other examples, the core community microbial species in the composition comprises at least one of the following species: Dysosmobacter welbionis, Enterocloster bolteae, Ruthenibacterium lactatiformans, Vescimonas coprocola, Phocaeicola salanitronis, Pusillimonas faecalis, Solibaculum mannosilyticum, Chrstensenella minuta, Alistipes magaguti, Parabacteroides goldsteinii, Alistipes communis, Ruminococcus bicirculans,Bacteroides caecimuris, Alistipes dispar, and Bacteroides salversiae. In another example, the keystone microbial species in the composition comprises at least one of the following species: Phocaeicola coprocola, Bifidobacterium bifidum, and Coprococcus catus. In another example, the core community microbial species in the composition comprises at least one of the following species: Alistipes dispar, Bacteroides salyersiae, Bifidobacterium bifidum, Christensenella minuta, Coprococcus catus, Coprococcus spOO0154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis, Parabacteroides goldsteinii, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, and Vescimonas coprocola.

[0017] In other examples, compositions of the disclosure are defined based on a ratio of core community species or strains relative to keystone species or strains (e.g. core community species: keystone species), In an example, the ratio of core community species to keystone species is 10:1. In another example, the ratio is 5:1. In another example, the ratio is 3:1. In an example, the ratio of core community strains to keystone species is 10:1. In another example, the ratio is 5:1. In another example, the ratio is 3:1. In these examples, the respective ratio may be established based on selection from Tables 13 and 14. In other examples, the ratio may be based on selection from Table 31 or 33. For example, the ratio may be based on selection from Table 33. In another example, the ratio may be based on selection from Table 34. In another example, the ratio may be based on selection from Table 35. . In another example, the ratio may be based on selection from Table 36.

[0018] In certain examples, compositions of the disclosure are defined based on a threshold selection of species or strains from a list disclosed herein (e.g. a % of a particular list). For example, compositions of the disclosure may comprise between 80 to 100% of the species identified on Tables 4 and 5. In another example, compositions of the disclosure may comprise between 80 to 100% of the species identified on Table 15. In another example, compositions of the disclosure may comprise between 80 to 100% of the species identified on Table 31. In another example, compositions of the disclosure may comprise between 80 to 100% of the species identified on Table 33. In another example, compositions of the disclosure may comprise between 80 to 100% of the species identified on Table 34. In another example, compositions of the disclosure may comprise between 80 to 100% of the species identified on Table 35. In another example, compositions of the disclosure may comprise between 80 to 100% of the species identified on Table 36. In another example, compositions of the disclosure may comprise between 80 to 100% of the strains identified on Table 15. In another example, compositions of the disclosure may comprise between 80 to 100% of the strains identified on Table 31. In another example, compositions of the disclosure may comprise between 80 to 100% of the strains identified on Table 33. In another example, compositions of the disclosure may comprise between 80 to 100% of the strains identified on Table 34. In another example, compositions of the disclosure may comprise between 80 to100% of the strains identified on Table 35. In another example, compositions of the disclosure may comprise between 80 to 100% of the strains identified on Table 36. In certain examples, these compositions are culture expanded, wherein the relevant % of species / strains is assessed based on the species or strains that are present in the culture expanded composition. In other examples, such as where a composition is (or is intended for use as) an inoculum, the relevant % is assessed based on the species or strains that are present in the inoculum, noting that this % may not necessarily be reflected in a culture expanded composition derived therefrom.

[0019] In other examples, compositions of the disclosure are characterized based on species or strains with certain V3-V4 16S sequences. For example, compositions of the disclosure may comprise core and keystone strains characterized by a V3-V416S sequence set forth in SEQ ID NO: 1 to 143 or 287 to 295. In other example, compositions of the disclosure may comprise core and keystone strains characterized by a V3-V416S sequences set forth in SEQ ID NOs: 2, 4-6, 9, 10, 12, 18, 21 -24, 26-30, 32, 34-40, 44-46, 48, 49, 51 -53, 56-58, 60, 64-74, 76- 83, 86, 89-94, 96- 100, 103- 106, 108, 110- 112, 115- 118, 122 - 125, 127, 128, 133 - 136, 138, 139, 143. In other example, compositions of the disclosure may comprise core and keystone strains characterized by a V3-V416S sequences set forth in SEQ ID NOs: 2, 4-6, 9, 10, 12, 18, 21 -24, 26-30, 32, 34-40, 44-46, 48, 49, 51 -53, 56-58, 60, 64-74, 76- 83, 86, 89-94, 96- 100, 103- 106, 108, 110- 112, 115- 118, 122 - 125, 127, 128, 133 - 136, 138, 139, 143, 287 - 295. In other examples, compositions of the disclosure are characterized based on species or strains with certain full length 16S sequences. For example, compositions of the disclosure may comprise core and keystone strains characterized a full length 16S sequences set forth in SEQ ID NOs: 144 to 286 or 296 to 303. In other example, compositions of the disclosure may comprise core and keystone strains characterized by a full length sequences set forth in SEQ ID NOs: 145 - 149, 152, 153, 155, 161, 164,165- 167, 169- 173, 175, 177- 183, 188, 189, 191, 192, 194- 196, 199 - 201, 203, 207 - 217, 219 - 226, 229, 232 - 237, 239 - 243, 246 - 249, 251, 253 - 255, 258 - 261, 265 - 268, 270, 271, 277 - 279, 281, 282, 285, 286. In other example, compositions of the disclosure may comprise core and keystone strains characterized by a full length sequences set forth in SEQ ID NOs: 145- 149, 152, 153, 155, 161, 164,165- 167, 169- 173, 175, 177- 183, 188, 189, 191, 192, 194- 196, 199-201, 203, 207-217, 219-226, 229, 232 - 237, 239 - 243, 246 - 249, 251, 253 - 255, 258 - 261, 265 - 268, 270, 271, 277 - 279, 281, 282, 285, 286, 296 - 303.

[0020] In an example, compositions of the disclosure may be characterised by a microbe threshold, wherein a certain percentage of microbes disclosed herein must be present irrespective of the number of microbes in the resulting composition. In an example, between 40% and 80% of the microbial strains in a composition of the disclosure are core and keystone from Table 34 or Table 35. In another example, between 40 and 80% of the microbial strainsin a composition of the disclosure are core and keystone strains characterized by a V3-V4 16S sequence set forth in SEQ ID NO: 1 to 143 or 287 to 295. In another example, between 40 and 80% of the microbial strains in a composition of the disclosure are core and keystone strains characterized by a full length 16S sequences set forth in SEQ ID NOs: 144 to 286 or 296 to 303.

[0021] In other examples compositions of the disclosure do not comprise any bacteria from the phylum Pseudomonadota or Campylobacterota.

[0022] The formulations and compositions of the disclosure may be used, in some embodiments, to treat mycobiome dysbiosis. For example, the formulations are used in some embodiments to treat ulcerative colitis, inflammatory bowel disease, Crohn’s disease, checkpoint inhibitor colitis, as well as other gastrointestinal diseases and symptoms. The formulations are used in some embodiments to treat liver disorders, including, for example, primary sclerosing cholangitis, non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, alcoholic hepatitis, or hepatic encephalopathy. The formulations are used in some embodiments to treat metabolic disorders, including, for example, obesity, insulin resistance, or type 2 diabetes. The formulations are used in some embodiments to treat oncology indications, including, for example, melanoma, renal cell carcinoma, bowel cancer and precancerous polyps, lymphoma, leukemia, myeloma, pancreatic cancer, breast cancer, lung cancer, testicular cancer, or sarcoma. The formulations are used in some embodiments to treat cardiovascular disorders, including, for example, dyslipidaemia, atherosclerotic heart disease, or hypertension. The formulations are used in some embodiments to treat immunological diseases, including, for example, type 1 diabetes, rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematous, or Sjogren’s disease. The formulations are used in some embodiments to treat allergic and atopic disorders, including, for example, food allergy, anaphylaxis, atopic dermatitis, or atopic rhinitis or sinusitis. The formulations are used in some embodiments to treat infectious diseases, including, for example, clostridioides difficile infection, multidrug resistant infection or colonisation, renal tract or urinary tract infections, blood stream infections, respiratory infections, or sepsis. Enhancement of the immune system is provided by several formulations. In some embodiments, the formulations reduce adhesion and / or colonization of pathogenic microbes (such as pathogenic or undesired bacteria, viruses, and / or yeast and other fungi). In some embodiments, restoration of a health gut ecology treats diseases and symptoms that are not considered traditional gastrointestinal diseases. For example, neurological disorders, including for example, autism, multiple sclerosis, Parkinson’s disease, depression, anxiety, bipolar disorder, or schizophrenia, and other conditions may be treated by restoring a healthier microbiome. In some embodiments, the formulations are formulated to treat one or more of the diseases or disorders described herein, including any combination thereof. In some embodiments, the formulations are used in combination with a therapy to treat any of the diseases or disorders described herein.

[0023] In an example, compositions of the disclosure are used for treatment of a dysbiosis. In another example, compositions of the disclosure are used for treatment of an inflammatory bowel disease (IBD). In an example, the IBD is ulcerative colitis. In an example, the IBD is Crohn’s disease. In an example, the IBD is gastroenteritis; colitis; or pouchitis.

[0024] In some embodiments, the formulation comprises or consists essentially of a consortium of core and keystone bacterial strains that replicates at least 90% of the gene families that are found in a healthy microbiome. In other embodiments, replication of 50%- 90% of the gene families is provided.

[0025] In several embodiments, a formulation or composition of the disclosure comprises or consists essentially of 5-26 core community microbial strains selected from Table 14 and 5-22 or more keystone microbial strains selected from Table 13. The formulations are cocultured, lyophilized and provided as an oral formulation (e.g., a capsule, tablet, or powder) in several embodiments. One or more of enteric coatings, pharmaceutically acceptable excipients (e.g., inulin and / or maltodextrin) and fibres are also provided (which may be natural or non-naturally occurring, e.g., partially or fully modified, synthetic, etc.). Agents to balance pH may also be included. For example, in some embodiments, the formulation comprises or consists essentially of any 10 or more of Bifidobacterium longum, Faecalibacterium prausnitzii, Dysosmobacter welbionis, Enterocloster bolteae, Alistipes megaguti, Parabacteroides goldsteinii, Flavonifractor plautii, Alistipes communis, Ruthenibacterium lactatiformans, Vescimonas coprocola, Collinsella aerofaciens, Coprococcus comes, Ruminococcus gnavus, Ruminococcus bicirculans, Bacteroides caecimuris, Coprococcus eutactus, Butyricimonas virosa, Phocaeicola salanitronis, Alistipes dispar, Clostridium scindens, Parabacteroides merdae, Bacteroides salyersiae, Pusillimonas faecalis, Solibaculum mannosilyticum, Akkermansia muciniphila, or Christensenella minuta in combination with any 10 or more of Bifidobacterium longum, Faecalibacterium prausnitzii, Bifidobacterium bifidum, Alistipes putredinis, Alistipes shahii, Bacteroides intestinalis, Bacteroides stercoris, Bifidobacterium adolescentis, Coprococcus catus, Methonobrevibacter smithii, Parabacteroides johnsonii, Phocaeicola coprocola, Roseburia inulinivorans, Ruminococcus bromii, Ruminococcus torques, Subdoligranulum variabile, Bacteroides caccae, Bacteroides coprocola, Bacteroides eggerthii, Bacteroides thetaiotaomicron, Bacteroides uniformis, or Parabacteroides distasonis, and one or more of an enteric coating, inulin, or maltodextrin. In some embodiments, 5-10, 10-15, 15-26 core community strains (e.g., from Table 14) and 5-10, ID- 15, 15-22 keystone strains (e.g., from Table 13) are co-cultured together and / or in the formulation for administration to a subject. In some embodiments, 90, 92, 95% or all of the core community strains and all of the keystones strains are co-cultured together and / or in the formulation for administration to a subject. Certain strains may be valuable in the co-culture to support the community as a whole but may not be present in the formulation for administrationto a subject. In some embodiments, about 5-20% of strains that are in the co-culture are not significantly present in the formulation for administration to a subject.

[0026] In some embodiments, the formulation comprises or consists essentially of (i) 85- 90%, 90%-95%, or all of the core community microbial strains in Table 14 and / or (ii) 85-90%, 90%-95% or all of the keystone microbial strains selected from Table 13. In several embodiments, the formulation comprises or consists essentially of 20-26 core community microbial strains selected from Table 14, and keystone strains from Table 13 at a core:keystone strain ratio at 10: 1. 9:1 , 8:1 , 7:1 , 6:1 , 5:1 , 4:1 , 3:1 , 2:1 , or 1 :1. In some embodiments, the formulation comprises or consists essentially of from 50% to 80% core community microbial strains and from 20% to 50% keystone microbial strains as a percentage of total number or mass microorganisms in the formulation. In several embodiments, the core and keystone strains have been co-cultured together. With respect to the numbers, amounts and ratios disclosed herein, the formulation may be the formulation administered to a subject or in the co-culture.

[0027] In some embodiments, the formulations include a microbial consortium having bacteria selected from the phyla Actinomycetota, Bacillota, Bacteroidota, Campylobacterota, Pseudomonadota, Thermodesulfobiota, and Verrucomicrobiota. In some embodiments, the formulations include strains from Actinomycetota, Bacillota, Bacteroidota, and Verrucomicrobiota. In several embodiments, the formulations include strains from no more than two phyla of Actinomycetota, Bacillota, Bacteroidota, and Pseudomonadota. In several embodiments, the formulation (whether co-cultured or for administration to a subject) does not include bacteria from Pseudomonadota and / or Campylobacterota. In some embodiments, Pseudomonadota or Campylobacterota are completely or significantly excluded or removed from the formulations.

[0028] In some embodiments, the formulations described herein are used with other therapies. For example, the formulations may be used to reduce side effects of other pharmaceuticals (including e.g., biologies) by, for example, reducing the dose or course needed for such pharmaceutical, reducing an inflammatory response, reducing nausea or other undesired effect of such pharmaceutical post administration. The formulations may also be used to enhance the beneficial effects of other pharmaceuticals by, for example, increasing absorption and / or availability of such pharmaceutical post administration. In some embodiments, improved effects are achieved using the formulations described herein and other therapies such as pharmaceuticals.

[0029] In some embodiments, the formulations are used to restore a healthy microbiome after antibiotic therapy and / or cleanses and may be provided before, together with, or after antibiotic therapy and / or cleanses. In some embodiments, when treating a specific disease for example, antibiotics and / or cleanses may optionally be administered prior to administration ofthe formulation to assist in providing a “cleaner slate” for the consortium in the formulation. The cleanse may be associated with medical procedures such as colonoscopies.

[0030] In several embodiments, a composition comprising multiple core community microbial strains as well as multiple keystone microbial strains are provided to, for example, restore gut microbiome ecology. In some embodiments, the core community and keystone strains are co-cultured together to provide an improved consortium with diverse species. When administered to a subject, according to one embodiment, the consortium is capable of providing a beneficially stable microbial ecosystem because the various strains have already been co-cultured together prior to administration.

[0031] In some embodiments, a diverse range of gene families, as described herein, provides the ability to deliver therapies that have broad functional capability as well as highly targeted disease specific function. Oral compositions are provided in several embodiments, which in turn can eliminate the reliance on stool donors and enables production of microbial therapies at scale, to large markets. The compositions are used in some embodiments to treat mycobiome dysbiosis. For example, the compositions are used in some embodiments to treat ulcerative colitis, inflammatory bowel disease, Crohn’s disease, checkpoint inhibitor colitis, as well as other gastrointestinal diseases and symptoms. The compositions are used in some embodiments to treat liver disorders, including, for example, primary sclerosing cholangitis, non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, alcoholic hepatitis, or hepatic encephalopathy. The compositions are used in some embodiments to treat metabolic disorders, including, for example, obesity, insulin resistance, or type 2 diabetes. The compositions are used in some embodiments to treat oncology indications, including, for example, melanoma, renal cell carcinoma, bowel cancer and precancerous polyps, lymphoma, leukemia, myeloma, pancreatic cancer, breast cancer, lung cancer, testicular cancer, or sarcoma. The compositions are used in some embodiments to treat cardiovascular disorders, including, for example, dyslipidaemia, atherosclerotic heart disease, or hypertension. The compositions are used in some embodiments to treat immunological diseases, including, for example, type 1 diabetes, rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematous, or Sjogren’s disease. The compositions are used in some embodiments to treat allergic and atopic disorders, including, for example, food allergy, anaphylaxis, atopic dermatitis, or atopic rhinitis or sinusitis. The compositions are used in some embodiments to treat infectious diseases, including, for example, Clostridioides difficile infection, multidrug resistant infection or colonisation, renal tract or urinary tract infections, blood stream infections, respiratory infections, or sepsis. Enhancement of the immune system is provided by several compositions. In some embodiments, the compositions reduce adhesion and / or colonization of pathogenic microbes (such as pathogenic or undesired bacteria, viruses, and / or yeast and other fungi). In some embodiments, restoration of a health gut ecology treats diseases and symptoms that are not considered traditional gastrointestinaldiseases. For example, neurological disorders, including for example, autism, multiple sclerosis, Parkinson’s disease, depression, anxiety, bipolar disorder, or schizophrenia, and other conditions may be treated by restoring a healthier microbiome. In some embodiments, the compositions are formulated to treat one or more of the diseases or disorders described herein, including any combination thereof. In some embodiments, the compositions are used in combination with a therapy to treat any of the diseases or disorders described herein.

[0032] In some embodiments, the composition comprises or consists essentially of a consortium of core and keystone bacterial strains that replicates at least 90% of the gene families that are found in a healthy microbiome. In other embodiments, replication of 50%- 90% of the gene families is provided.

[0033] In several embodiments, a composition comprises or consists essentially of 5-26 core community microbial strains selected from Table 14 and 5-22 or more keystone microbial strains selected from Table 13. The compositions are co-cultured, lyophilized and provided as an oral composition (e.g., a capsule, tablet, or powder) in several embodiments. One or more of enteric coatings, pharmaceutically acceptable excipients (e.g., inulin and / or maltodextrin) and fibres are also provided (which may be natural or non-naturally occurring, e.g., partially or fully modified, synthetic, etc.). Agents to balance pH may also be included. For example, in some embodiments, the composition comprises or consists essentially of any 10 or more of Bifidobacterium longum, Faecalibacterium prausnitzii, Dysosmobacter welbionis, Enterocloster bolteae, Alistipes megaguti, Parabacteroides goldsteinii, Flavonifractor plautii, Alistipes communis, Rutheni bacterium lactatiformans, Vescimonas coprocola, Collinsella aerofaciens, Coprococcus comes, Ruminococcus gnavus, Ruminococcus bicirculans, Bacteroides caecimuris, Coprococcus eutactus, Butyricimonas virosa, Phocaeicola salanitronis, Alistipes dispar, Clostridium scindens, Parabacteroides merdae, Bacteroides salyersiae, Pusillimonas faecalis, Solibaculum mannosilyticum, Akkermansia muciniphila, or Christensenella minuta in combination with any 10 or more of Bifidobacterium longum, Faecalibacterium prausnitzii, Bifidobacterium bifidum, Alistipes putredinis, Alistipes shahii, Bacteroides intestinalis, Bacteroides stercoris, Bifidobacterium adolescentis, Coprococcus catus, Methonobrevibacter smithii, Parabacteroides johnsonii, Phocaeicola coprocola, Roseburia inulinivorans, Ruminococcus bromii, Ruminococcus torques, Subdoligranulum variabile, Bacteroides caccae, Bacteroides coprocola, Bacteroides eggerthii, Bacteroides thetaiotaomicron, Bacteroides uniformis, or Parabacteroides distasonis, and one or more of an enteric coating, inulin, or maltodextrin. In some embodiments, 5-10, 10-15, 15-26 core community strains (e.g., from Table 14) and 5-10, 10-15, 15-22 keystone strains (e.g., from Table 13) are co-cultured together and / or in the composition for administration to a subject. In some embodiments, 90, 92, 95% or all of the core community strains and all of the keystones strains are co-cultured together and / or in the composition for administration to a subject. Certain strains may be valuable in the co-culture to support the community as a whole butmay not be present in the composition for administration to a subject. In some embodiments, about 5-20% of strains that are in the co-culture are not significantly present in the composition for administration to a subject.

[0034] In some embodiments, the composition comprises or consists essentially of (i) 85- 90%, 90%-95%, or all of the core community microbial strains in Table 14 and / or (ii) 85-90%, 90%-95% or all of the keystone microbial strains selected from Table 13. In several embodiments, the composition comprises or consists essentially of 20-26 core community microbial strains selected from Table 14, and keystone strains from Table 13 at a core:keystone strain ratio at 10: 1. 9:1 , 8:1 , 7:1 , 6:1 , 5:1 , 4:1 , 3:1 , 2:1 , or 1 :1. In some embodiments, the composition comprises or consists essentially of from 50% to 80% core community microbial strains and from 20% to 50% keystone microbial strains as a percentage of total number or mass microorganisms in the composition. In several embodiments, the core and keystone strains have been co-cultured together.

[0035] With respect to the numbers, amounts and ratios disclosed herein, the composition may be the composition administered to a subject or in the co-culture.

[0036] In some embodiments, the compositions include a microbial consortium having bacteria selected from the phyla Actinomycetota, Bacillota, Bacteroidota, Campylobacterota, Pseudomonadota, Thermodesulfobiota, and Verrucomicrobiota. In some embodiments, the compositions include strains from Actinomycetota, Bacillota, Bacteroidota, and Verrucomicrobiota. In several embodiments, the compositions include strains from no more than two phyla of Actinomycetota, Bacillota, Bacteroidota, and Pseudomonadota. In several embodiments, the composition (whether co-cultured or for administration to a subject) does not include bacteria from Pseudomonadota and / or Campylobacterota. In some embodiments, Pseudomonadota or Campylobacterotaare completely or significantly excluded or removed from the compositions.

[0037] In some embodiments, the compositions described herein are used with other therapies. For example, the compositions may be used to reduce side effects of other pharmaceuticals (including e.g., biologies) by, for example, reducing the dose or course needed for such pharmaceutical, reducing an inflammatory response, reducing nausea or other undesired effect of such pharmaceutical post administration. The compositions may also be used to enhance the beneficial effects of other pharmaceuticals by, for example, increasing absorption and / or availability of such pharmaceutical post administration. In some embodiments, improved effects are achieved using the compositions described herein and other therapies such as pharmaceuticals.

[0038] In some embodiments, the compositions are used to restore a healthy microbiome after antibiotic therapy and / or cleanses and may be provided before, together with, or after antibiotic therapy and / or cleanses. In some embodiments, when treating a specific disease for example, antibiotics and / or cleanses may optionally be administered prior to administration ofthe composition to assist in providing a “cleaner slate” for the consortium in the composition. The cleanse may be associated with medical procedures such as colonoscopies.

[0039] In a further embodiment, the disclosure is a composition comprising a microbial consortium comprising at least one microbe, wherein the at least one microbe is selected from the group consisting of: bacteria and archaea; and wherein the at least one microbe is a member of a phylum, selected from the group consisting of: any one of the phyla listed in Table 1 ; any one of the phyla listed in Table 2; any one of the phyla listed in Table 3; and any combination, subgroup or multitude thereof.

[0040] In some embodiments, the microbial consortium comprises a plurality of microbes.

[0041] In some embodiments, the microbe is a member of a cladistic group selected from the groups consisting of: the cladistic groups presented in Figure 8 or any combination, subgroup or multitude thereof.

[0042] In some embodiments, the microbe is a member of a family selected from the group consisting of: any one of the families listed in Table 4; any one of the families listed in Table 5; any one of the families listed in Table 6; and any combination, subgroup or multitude thereof.

[0043] In some embodiments, the microbe is a member of a genus selected from the group consisting of: any one of the genera listed in Table 7; any one of the genera listed in Table 8; and any combination, subgroup or multitude thereof.

[0044] In some embodiments, the microbe is a member of a species selected from the group consisting of: any one of the species listed in Table 9; any one of the species listed in Table 10; any one of the species listed in Table 11 ; any one of the species listed in Table 12; any one of the species listed in Table 13; any one of the species listed in Table 14; any one of the species listed in Table 15; and any one of the species listed in Table 16; and any combination, subgroup or multitude thereof.

[0045] In some embodiments, the microbe is a member of a species selected from the group consisting of: any one of the microbial keystones listed in Table 13; and any combination, subgroup or multitude thereof.

[0046] In some embodiments, the microbe is a member of a species selected from the group consisting of: any one of the core community species listed in Table 14; and any combination, subgroup or multitude thereof.

[0047] In some embodiments, the microbe is a member of a species selected from the group consisting of: any one of the species listed in Table 15; and any combination, subgroup or multitude thereof.

[0048] In some embodiments, the microbe is a member of a species selected from the group consisting of: any one of the species listed in Table 16; and any combination, subgroup or multitude thereof.

[0049] In some embodiments, the microbe is selected from the group consisting of: any one of the microbes comprising SEQ ID NOs 1 to 143 or 287 to 295 which are the V3-V4 16S sequences; microbes comprising SEQ ID NOs 144 to 286 or 296 to 303 which are the full- length 16S rRNA gene sequences; the consortium presented in Figure 7; and any combination, subgroup or multitude thereof. These sequences are used for taxonomic classification of microbial species because the 16S rRNA gene, which is a small ribosomal subunit, is conserved amongst microbial species whilst containing hypervariable regions, such as the V3-V4 region, which provides sufficient variation to determine species-level discrimination between 16 rRNA gene sequences. The sequences presented are DNA sequences encoding the ribosomal RNA.

[0050] In some embodiments, the microbial consortium is selected from the group consisting of: the consortium of microbes comprising SEQ ID NOs 1 to 143 or 287 to 295 which are the V3-V4 16S sequences; the consortium of microbes comprising SEQ ID NOs 144 to 286 or 296 to 303 which are the full-length 16S rRNA gene sequences; the consortium presented in Figure 7; and any combination, subgroup or multitude thereof.

[0051] In some embodiments, the microbe has a nucleotide sequence selected from the group consisting of: any one of the Sanger Sequencing 16S ribosomal RNA (rRNA) genes as presented in SEQ ID NOs: 1 to 286; and any combination, subgroup or multitude thereof.

[0052] In some embodiments, the microbe comprises a 16S ribosomal RNA (rRNA) gene having a nucleotide sequence selected from the group consisting of: any one of the V3-V4 16S sequences presented in SEQ ID NOs: 1 to 143 or 287 to 295; any one of the full length 16S sequences presented in SEQ ID NOs: 144 to 286 or 296 to 303; and any combination, subgroup or multitude thereof. In an example, the 16S rRNA sequence is assessed or determined based on whole genome sequencing (or the output thereof, which may be in a publicly available database).

[0053] The 16S rRNA sequence is an accepted marker for identifying and classifying microorganisms due to its highly conserved nature and variable regions that allow for the differentiation between species. However, as would be appreciated by those of skill in the art, minor variations in 16S rRNA sequence may be observed, depending on the sequencing method employed, for the same microbe (e.g. species or strain). Accordingly, in some embodiments, corresponding microbes may have a 16S rRNA sequence that is at least 99.9% identical to a SEQ ID NO: disclosed herein. In another example, the 16s rRNA sequence is at least 99.5% identical to a SEQ ID NO: disclosed herein. In another example, the 16s rRNA sequence is at least 99% identical to a SEQ ID NO: disclosed herein. In another example, the 16s rRNA sequence is at least 98.5% identical to a SEQ ID NO: disclosed herein. In another example, the 16s rRNA sequence is at least 98% identical to a SEQ ID NO: disclosed herein.

[0054] In other examples, the corresponding 16S rRNA sequence has sequence identity selected from the any one of the groups consisting of: at least 97.5%; at least 97%; at least96.5%; at least 96%; at least 95.5%; at least 95%; at least 94.5%; at least 94%; at least 93.5%; at least 93%; at least 92.5%; at least 92%; at least 91.5%; at least 91%; at least 90.5% and at least 90%.

[0055] In some embodiments, the microbial consortium comprises any one of the communities presented in: Table 9; Table 10; Table 11 ; Table 12; Table 13; Table 14; Table 15; Table 16. In other embodiments, the microbial consortium comprises any one of the communities presented in: Table 33; Table 34; Table 35; Table 36.

[0056] In some embodiments, the microbial consortium comprises at least the keystones presented in Table 13.

[0057] In some embodiments, the microbial consortium comprises at least the minimum core species presented in Table 14.

[0058] In some embodiments, the microbial consortium is the consortium of 143 members presented in Figure 7 (also known as BB265).

[0059] In some embodiments, the microbial consortium is the consortium of 127 members presented in Figure 20.

[0060] In some embodiments, the microbial consortium comprises a supportive community of microbial species, strains or isolates.

[0061] In some embodiments, the composition comprises a plurality of core community microbial species, wherein said core community microbial species comprise members of at least the following genera selected from the group consisting of: Dysosmobacter; Enterocloster; Ruthenibacterium; Vescimonas; Phocaeicola; Pusillimonas; Solibaculum; and Christensenella, a plurality of keystone microbial species, wherein said keystone microbial species comprise members of at least the genus Phocaeicola', and any combination, subgroup or multitude thereof.

[0062] In some embodiments, the composition comprises a plurality of core community microbial species, wherein said core community microbial species comprise at least one of the following species selected from the group consisting of: Alistipes dispar; Bacteroides salyersiae; Bifidobacterium bifidum; Christensenella minuta; Coprococcus catus; Coprococcus spOO0154245; Dysosmobacter faecalis; Faecalibacterium duncaniae; Gemmiger formicilis; Parabacteroides goldsteinii; Ruminococcus bicirculans; Ruthenibacterium lactatiformans; Solibaculum mannosilyticum; and Vescimonas coprocola', and any combination, subgroup or multitude thereof.

[0063] In some embodiments, the plurality of core community microbial species comprises at least one of the following species selected from the group consisting of: Dysosmobacter welbionis; Enterocloster bolteae; Ruthenibacterium lactatiformans; Vescimonas coprocola; Phocaeicola salanitronis; Pusillimonas faecalis; Solibaculum mannosilyticum; Chrstensenella minuta; Alistipes magaguti; Parabacteroides goldsteinii, Alistipes communis; Ruminococcus bicirculans; Bacteroides caecimuris; Alistipes dispar, andBacteroides salversiae’, and wherein the plurality of keystone microbial species comprises at least one of the following species: Phocaeicola coprocola; Bifidobacterium bifidum; and Coprococcus catus and any combination, subgroup or multitude thereof.

[0064] In some embodiments, the plurality of core community microbial species comprises at least the following species: Dysosmobacter welbionis; Enterocloster bolteae; Ruthenibacterium lactatiformans; Vescimonas coprocola; Phocaeicola salanitronis; Pusillimonas faecalis; Solibaculum mannosilyticum; Chrstensenella minuta; Alistipes magaguti; Para bacteroides goldsteinii, Alistipes communis; Ruminococcus bicirculans; Bacteroides caecimuris; Alistipes dispar, and Bacteroides salversiae’, and any combination, subgroup or multitude thereof.

[0065] In some embodiments, the plurality of keystone microbial species comprises: Phocaeicola coprocola; Bifidobacterium bifidum; and Coprococcus catus and any combination, subgroup or multitude thereof.

[0066] In some embodiments, the composition comprises a plurality of core community microbial species, wherein said core community microbial species is selected from the group consisting of: Alistipes dispar; Bacteroides salyersiae; Bifidobacterium bifidum; Christensenella minuta; Coprococcus catus; Coprococcus spOO0154245; Dysosmobacter faecalis; Faecalibacterium duncaniae; Gemmiger formicilis; Parabacteroides goldsteinii; Ruminococcus bicirculans; Ruthenibacterium lactatiformans; Solibaculum mannosilyticum; and Vescimonas coprocola’, and any combination, subgroup or multitude thereof.

[0067] In some embodiments, the plurality of core community microbial species is selected the group consisting of: Dysosmobacter welbionis; Enterocloster bolteae; Ruthenibacterium lactatiformans; Vescimonas coprocola; Phocaeicola salanitronis; Pusillimonas faecalis; Solibaculum mannosilyticum; Chrstensenella minuta; Alistipes magaguti; Parabacteroides goldsteinii, Alistipes communis; Ruminococcus bicirculans; Bacteroides caecimuris; Alistipes dispar, and Bacteroides salversiae’, and wherein the plurality of keystone microbial species is selected from the group consisting of: Phocaeicola coprocola; Bifidobacterium bifidum; and Coprococcus catus’, and any combination, subgroup or multitude thereof.

[0068] In some embodiments, the composition comprises a plurality of core community microbial species, wherein said core community microbial species comprises: Alistipes dispar; Bacteroides salyersiae; Bifidobacterium bifidum; Christensenella minuta; Coprococcus catus; Coprococcus spOO0154245; Dysosmobacter faecalis; Faecalibacterium duncaniae; Gemmiger formicilis; Parabacteroides goldsteinii; Ruminococcus bicirculans; Ruthenibacterium lactatiformans; Solibaculum mannosilyticum; and Vescimonas coprocola’, and any combination, subgroup or multitude thereof.

[0069] In some embodiments, the plurality of core community microbial species comrpises: Dysosmobacter welbionis; Enterocloster bolteae; Ruthenibacteriumlactatiformans; Vescimonas coprocola; Phocaeicola salanitronis; Pusillimonas faecalis; Solibaculum mannosilyticum; Chrstensenella minuta; Alistipes magaguti; Parabacteroides goldsteinii, Alistipes communis; Ruminococcus bicirculans; Bacteroides caecimuris; Alistipes dispar, and Bacteroides salversiae', and wherein the plurality of keystone microbial species comprises: Phocaeicola coprocola; Bifidobacterium bifidum; and Coprococcus catus and any combination, subgroup or multitude thereof.

[0070] In some embodiments, the microbial consortium does not comprise any bacteria from the phylum Pseudomonadota or Campylobacterota.

[0071] In some embodiments, the microbial consortium does not comprise one or more species selected from the group consisting of: Absiella dolichum; Acidaminococcus fermentans; Acidaminococcus sp.; Adlercreutzia equolifaciens; Agathobacter rectalis; Akkermansia muciniphila; Alistipes finegoldii; Alistipes indistinctus; Alistipes onderdonkii; Alistipes putredinis; Alistipes senegalensis; Alistipes shahii; Amedibacillus dolichus; Anaerobutyricum hallii; Anaerofustis stercorihominis; Anaerostipes caccae; Anaerotruncus colihominis; Faecal i bacterium prausnitzii; Solobacterium moorei; Bacteroides; Bacteroides cacaea; Bacteroides caccae; Bacteroides cellulosilyticus; Bacteroides coprocola; Bacteroides coprophilus; Bacteroides dorea; Bacteroides dorei; Bacteroides eggerthii; Bacteroides finegoldii; Bacteroides fragilis; Bacteroides intestinalis; Bacteroides ovatus; Bacteroides pectinophilus; Bacteroides plebeius; Bacteroides rodentium; Bacteroides stercoris; Bacteroides thetaiotaomicron; Bacteroides uniformis; Bacteroides vulgatus; Bacteroides xylanisolvens; Bifidobacterium breve; Bifidobacterium catenulatum; Bifidobacterium pseudocatenulatum; Bilophila wadsworthia; Blautia hansenii; Blautia hydrogenotrophica; Blautia obeum; Blautia sp.; Blautia wexlerae; Butyricimonas virosa; Butyrivibrio crossotus; Catenibacterium mitsuokai; Clostridium asparagiforme; Clostridium bolteae; Clostridium hiranonis; Clostridium hylemonae; Clostridium leptum; Clostridium methylpentosum; Clostridium nexile; Clostridium orbiscindens; Clostridium saccharolyticum; Clostridium scindens; Clostridium sp.; Clostridium spiroforme; Collinsella aerofaciens; Collinsella stercoris; Copracoccus comes; Coprococcus eutactus; Desulfovibrio piger; Dialister invisus; Dorea formicigenerans; Eggerthella lenta; Enterocloster asparagiformis; Enterocloster bolteae; Ethanoligenens harbinense; Eubacterium rectale; Eubacterium siraeum; Eubacterium ventriosum; Flavonifractor plautii; Granulicatella adiacens; Granulicatella adiacens adiacens; Holdemanella biformis; Holdemania filiformis; Hoylesella buccalis; Hungatella hathewayi; Intestinibacter bartlettii; Intestinimonas butyriciproducens; Lacrimispora saccharolytica; Lactobacillus ruminis; Ugilactobacillus ruminis; Marvinbryantia formatexigens; Mediterraneibacter gnavus; Megasphaera sp.; Mitsuokella multacida; Odoribacter splanchnicus; Olsenella uli; Oscillibacter sp.; Parabacteroides distasonis; Parabacteroides johnsonii; Parabacteroides merdae; Parabacteroides sp.; Peptacetobacter hiranonis; Phocaeicola coprocola; Phocaeicola coprophilus; Phocaeicola dorei; Phocaeicolaplebeius; Phocaeicola vulgatus; Prevotella buccalis; Prevotella copri; Roseburia inulinivorans; Ruminococcus gauvreauii; Ruminococcus gnavus; Ruminococcus lactaris; Ruminococcus torques; Segatella copri; Slackia exigua; Slackia heliotrinireducens; Streptococcus salivarius; Streptococcus salivarius subsp. thermophilus; Streptococcus thermophilus; Subdoligranulum variabile; Thomasclavelia spiroformis; Turicibacter sanguinis; Tyzzerella nexilis', and any combination, subgroup or multitude thereof.

[0072] In some embodiments, the microbial consortium is generated by co-culturing the minimum core species and the keystone species in a single bioreactor.

[0073] In some embodiments, the microbial consortium comprises a ratio of minimum core species to keystone species of 10:1. 9:1 , 8:1 , 7:1 , 6:1 , 5:1 , 4:1 , 3:1 , 2:1 , or 1 :1 with respect to number of microbes.

[0074] In some embodiments, the microbial consortium comprises from 50% to 80% core community microbial strains and from 20% to 50% keystone microbial strains as a percentage of total microorganisms in the formulation.

[0075] In some embodiments, the microbial consortium comprises from A% to B% minimum core species and from C% to D% keystone species as a percentage of total microorganisms in the formulation, wherein the A% to B% range is selected from the group consisting of: 10% to 99%; 10% to 90%; 20% to 80%; 30% to 70%; 40% to 60%; 50% to 80%; and 20% to 50%; and wherein the C% to D% range is selected from the group consisting of: 10% to 99%; 10% to 90%; 20% to 80%; 30% to 70%; 40% to 60%; 50% to 80%; and 20% to 50%.

[0076] In some embodiments, the microbial consortium comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from Table 14 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 13. In other embodiments, the microbial consortium comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from Table 34 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 34. In other embodiments, the microbial consortium comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from Table 35 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 35. In other embodiments, the microbial consortium comprises all core community microbial strains selected from Table 36 and all keystone microbial strains selected from Table 36.

[0077] In some embodiments, the microbial consortium comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25 or all minimum core species selected from Table 14 and 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , or all keystone species selected from Table 13.

[0078] In some embodiments, the microbial consortium comprises 20 or more minimum core species selected from Table 14 and 10 or more keystone species selected from Table 13.

[0079] In some embodiments, the microbial consortium comprises a plurality of minimum core species and a plurality of keystone species comprising 80-100% of the species identified on Table 9; Table 10; Table 11 ; Table 12; Table 13; Table 14; Table 15; or Table 16. In some embodiments, the microbial consortium comprises a plurality of minimum core species and a plurality of keystone species comprising 80-100% of the species identified on Table 33, Table 34, Table 35 or Table 36.

[0080] In some embodiments, the microbial consortium comprises between 1 to 1000 microbial species, strains or isolates.

[0081] In some embodiments, the microbial consortium comprises any number between and including 1 to 1000 microbial species, strains or isolates, wherein the number is selected from the group consisting of: 1 ; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11 ; 12; 13; 14; 15; 16; 17; 18; 19; 20;21 ; 22; 23; 24; 25; 26; 27; 28; 29; 30; 31 ; 32; 33; 34; 35; 36; 37; 38; 39; 40; 41 ; 42; 43; 44; 45;46; 47; 48; 49; 50; 51 ; 52; 53; 54; 55; 56; 57; 58; 59; 60; 61 ; 62; 63; 64; 65; 66; 67; 68; 69; 70;71 ; 72; 73; 74; 75; 76; 77; 78; 79; 80; 81 ; 82; 83; 84; 85; 86; 87; 88; 89; 90; 91 ; 92; 93; 94; 95;96; 97; 98; 99; 100; 101 ; 102; 103; 104; 105; 106; 107; 108; 109; 110; 111 ; 112; 113; 114;115; 116; 117; 118; 119; 120; 121 ; 122; 123; 124; 125; 126; 127; 128; 129; 130; 131 ; 132;133; 134; 135; 136; 137; 138; 139; 140; 141 ; 142; 143; 144; 145; 146; 147; 148; 149; 150;151 ; 152; 153; 154; 155; 156; 157; 158; 159; 160; 161 ; 162; 163; 164; 165; 166; 167; 168;169; 170; 171 ; 172; 173; 174; 175; 176; 177; 178; 179; 180; 181 ; 182; 183; 184; 185; 186;187; 188; 189; 190; 191; 192; 193; 194; 195; 196; 197; 198; 199; 200; 201 ; 202; 203; 204;205; 206; 207; 208; 209; 210; 211 ; 212; 213; 214; 215; 216; 217; 218; 219; 220; 221 ; 222;223; 224; 225; 226; 227; 228; 229; 230; 231 ; 232; 233; 234; 235; 236; 237; 238; 239; 240;241 ; 242; 243; 244; 245; 246; 247; 248; 249; 250; 251 ; 252; 253; 254; 255; 256; 257; 258;259; 260; 261 ; 262; 263; 264; 265; 266; 267; 268; 269; 270; 271 ; 272; 273; 274; 275; 276;277; 278; 279; 280; 281; 282; 283; 284; 285; 286; 287; 288; 289; 290; 291 ; 292; 293; 294;295; 296; 297; 298; 299; 300; 301 ; 302; 303; 304; 305; 306; 307; 308; 309; 310; 311 ; 312;313; 314; 315; 316; 317; 318; 319; 320; 321 ; 322; 323; 324; 325; 326; 327; 328; 329; 330;331 ; 332; 333; 334; 335; 336; 337; 338; 339; 340; 341 ; 342; 343; 344; 345; 346; 347; 348;349; 350; 351 ; 352; 353; 354; 355; 356; 357; 358; 359; 360; 361 ; 362; 363; 364; 365; 366;367; 368; 369; 370; 371; 372; 373; 374; 375; 376; 377; 378; 379; 380; 381 ; 382; 383; 384;385; 386; 387; 388; 389; 390; 391 ; 392; 393; 394; 395; 396; 397; 398; 399; 400; 401 ; 402;403; 404; 405; 406; 407; 408; 409; 410; 411 ; 412; 413; 414; 415; 416; 417; 418; 419; 420;421 ; 422; 423; 424; 425; 426; 427; 428; 429; 430; 431 ; 432; 433; 434; 435; 436; 437; 438;439; 440; 441 ; 442; 443; 444; 445; 446; 447; 448; 449; 450; 451 ; 452; 453; 454; 455; 456;457; 458; 459; 460; 461; 462; 463; 464; 465; 466; 467; 468; 469; 470; 471 ; 472; 473; 474;475; 476; 477; 478; 479; 480; 481 ; 482; 483; 484; 485; 486; 487; 488; 489; 490; 491 ; 492;493; 494; 495; 496; 497; 498; 499; 500; 501 ; 502; 503; 504; 505; 506; 507; 508; 509; 510;511 ; 512; 513; 514; 515; 516; 517; 518; 519; 520; 521 ; 522; 523; 524; 525; 526; 527; 528;529; 530; 531; 532; 533; 534; 535; 536; 537; 538; 539; 540; 541 ; 542; 543; 544; 545; 546;547; 548; 549; 550; 551; 552; 553; 554; 555; 556; 557; 558; 559; 560; 561; 562; 563; 564;565; 566; 567; 568; 569; 570; 571; 572; 573; 574; 575; 576; 577; 578; 579; 580; 581; 582;583; 584; 585; 586; 587; 588; 589; 590; 591; 592; 593; 594; 595; 596; 597; 598; 599; 600;601; 602; 603; 604; 605; 606; 607; 608; 609; 610; 611; 612; 613; 614; 615; 616; 617; 618;619; 620; 621; 622; 623; 624; 625; 626; 627; 628; 629; 630; 631 ; 632; 633; 634; 635; 636;637; 638; 639; 640; 641; 642; 643; 644; 645; 646; 647; 648; 649; 650; 651; 652; 653; 654;655; 656; 657; 658; 659; 660; 661; 662; 663; 664; 665; 666; 667; 668; 669; 670; 671; 672;673; 674; 675; 676; 677; 678; 679; 680; 681; 682; 683; 684; 685; 686; 687; 688; 689; 690;691; 692; 693; 694; 695; 696; 697; 698; 699; 700; 701; 702; 703; 704; 705; 706; 707; 708;709; 710; 711; 712; 713; 714; 715; 716; 717; 718; 719; 720; 721 ; 722; 723; 724; 725; 726;727; 728; 729; 730; 731; 732; 733; 734; 735; 736; 737; 738; 739; 740; 741; 742; 743; 744;745; 746; 747; 748; 749; 750; 751; 752; 753; 754; 755; 756; 757; 758; 759; 760; 761; 762;763; 764; 765; 766; 767; 768; 769; 770; 771; 772; 773; 774; 775; 776; 777; 778; 779; 780;781; 782; 783; 784; 785; 786; 787; 788; 789; 790; 791; 792; 793; 794; 795; 796; 797; 798;799; 800; 801; 802; 803; 804; 805; 806; 807; 808; 809; 810; 811 ; 812; 813; 814; 815; 816;817; 818; 819; 820; 821; 822; 823; 824; 825; 826; 827; 828; 829; 830; 831; 832; 833; 834;835; 836; 837; 838; 839; 840; 841; 842; 843; 844; 845; 846; 847; 848; 849; 850; 851; 852;853; 854; 855; 856; 857; 858; 859; 860; 861; 862; 863; 864; 865; 866; 867; 868; 869; 870;871; 872; 873; 874; 875; 876; 877; 878; 879; 880; 881; 882; 883; 884; 885; 886; 887; 888;889; 890; 891; 892; 893; 894; 895; 896; 897; 898; 899; 900; 901 ; 902; 903; 904; 905; 906;907; 908; 909; 910; 911; 912; 913; 914; 915; 916; 917; 918; 919; 920; 921; 922; 923; 924;925; 926; 927; 928; 929; 930; 931; 932; 933; 934; 935; 936; 937; 938; 939; 940; 941; 942;943; 944; 945; 946; 947; 948; 949; 950; 951; 952; 953; 954; 955; 956; 957; 958; 959; 960;961; 962; 963; 964; 965; 966; 967; 968; 969; 970; 971; 972; 973; 974; 975; 976; 977; 978;979; 980; 981; 982; 983; 984; 985; 986; 987; 988; 989; 990; 991 ; 992; 993; 994; 995; 996;997; 998; 999; and 1000, or number within a range defined by any two of the aforementioned values.

[0082] In some embodiments, the microbial consortium comprises between 500 to 1000 microbial species, strains or isolates.

[0083] In some embodiments, the microbial consortium comprises between 200 to 500 microbial species, strains or isolates.

[0084] In some embodiments, the microbial consortium comprises between 20 to 200 microbial species, strains or isolates.

[0085] In some embodiments, the microbial consortium comprises between 130 to 140 microbial species, strains or isolates.

[0086] In some embodiments, the microbial consortium comprises between 120 to 130 microbial species, strains or isolates.

[0087] In some embodiments, the microbial consortium comprises between 110 to 120 microbial species, strains or isolates.

[0088] In some embodiments, the microbial consortium comprises between 100 to 110 microbial species, strains or isolates.

[0089] In some embodiments the microbial consortium comprises between 80 to 90 microbial species, strains or isolates.

[0090] In some embodiments, the microbial consortium comprises between 70 to 80 microbial species, strains or isolates.

[0091] In some embodiments, the microbial consortium comprises between 10 to 70 microbial species, strains or isolates.

[0092] In some embodiments, the microbial consortium comprises between 10 to 60 microbial species, strains or isolates.

[0093] In some embodiments, the microbial consortium comprises between 10 to 50 microbial species, strains or isolates.

[0094] In some embodiments, the microbial consortium comprises between 10 to 25 microbial species, strains or isolates.

[0095] In some embodiments, the microbial consortium comprises between 15 to 25 microbial species, strains or isolates.

[0096] In some embodiments, the microbial consortium comprises between 5 to 25 microbial species, strains or isolates.

[0097] In some embodiments, the microbial consortium comprises between 5 to 20 microbial species, strains or isolates.

[0098] In some embodiments, the microbial consortium comprises between 5 to 15 microbial species, strains or isolates.

[0099] In some embodiments, the microbial consortium comprises between 1 to 10 microbial species, strains or isolates.

[0100] In some embodiments, the microbial consortium comprises between 1 to 5 microbial species, strains or isolates.

[0101] In some embodiments, the microbial consortium comprises 143 microbial species, strains or isolates.

[0102] In some embodiments, the microbial consortium comprises 127 microbial species, strains or isolates.

[0103] In some embodiments, the number of microbial species, strains or isolates, is a minimum number required to achieve the desired level of functional potential or property.

[0104] In some embodiments, the minimum number is identified by the point on a rarefaction curve where the model’s asymptote intersects with the benchmark functional potential or property.

[0105] In some embodiments, the minimum number is identified by a method to estimate the minimum number of isolates required to achieve a desired level of functional potential or property in complex community therapeutics said method comprising the following steps:Step 1 - Isolate selection: Selecting a plurality of microbial isolates to comprise a target microbial community, wherein the isolates are representative of the genetic and functional diversity present within the community.Step 2 - Whole genome sequencing: Subjecting the selected microbial isolates to whole genome sequencing to obtain sequence data.Step 3 - Genome assembly and annotation: Assembling the obtained sequence data into complete or draft genomes for each isolate using a genome assembly pipeline, and subsequently annotating these genomes to identify functional gene categories, such as Clusters of Orthologous Genes (COGs) or equivalent functional annotations.Step 4 - Functional gene category identification: Identifying and cataloging the presence of functional gene categories within each genome based on the annotation results, wherein non-functional or non-essential categories, such as hypothetical proteins or tRNAs, are excluded from further analysis.Step 5 - Resampling and subset generation: Performing a resampling procedure on the annotated genomes, wherein subsets of isolates are randomly selected with replacement, covering a range of subset sizes from a single isolate to the total number of isolates in the community, to generate multiple iterations of isolate subsets.Step 6 - Functional potential assessment: For each subset generated in the resampling procedure, calculating the total number of unique functional gene categories present, thereby producing a dataset representing the functional potential or property of each subset size.Step 7 - Rarefaction curve construction: Constructing a rarefaction curve by plotting the number of unique functional gene categories against the number of isolates in each subset, wherein the curve depicts the relationship between the increasing number of isolates and the cumulative functional potential or property.Step 8 - Model fitting and asymptote determination: Fitting a mathematical model, such as a logistic or polynomial regression, to the rarefaction curve to determine the point at which the curve begins to asymptote, indicating a diminishing return in the discovery of new functional gene categories as additional isolates are added.Step 9 - Minimum viable consortium determination: Estimating the minimum number of isolates required to achieve a functional potential or property that meets or exceeds a predefined benchmark, such as the functional diversity present in a healthy or target microbial community, by identifying the point on the rarefaction curve where the model’s asymptote intersects with the benchmark functional potential or property.Step 10 - Application to therapeutic Design: Applying the results of the rarefaction analysis to design a minimal viable microbial consortium that retains the desired level of functional potential or property, ensuring that the consortium is both functionally robust and economically feasible for therapeutic applications.

[0106] In some embodiments, the microbe or plurality of microbes is a species or strain selected from any one of the species consisting of: any one of the microbes comprising SEQ ID NOs 1 to 143 or 287 to 295 which are the V3-V4 16S sequences; any one of the microbes comprising SEQ ID NOs 144 to 286 or 296 to 303 which are the full-length 16S rRNA gene sequences; and any one of the microbes in Figure 7; or any combination, subgroup or multitude thereof; and wherein composition further does not comprise a different microbe or plurality of microbes selected from any one of the species, strains or isolates consisting of: any one of the microbes comprising SEQ ID NOs 1 to 143 or 287 to 295 which are the V3-V4 16S sequences; any one of the microbes comprising SEQ ID NOs 144 to 286 or 296 to 303 which are the full-length 16S rRNA gene sequences; and any one of the microbes in Figure 7; or any combination, subgroup or multitude thereof.

[0107] In some embodiments, the microbe or plurality of microbes is a species or strain selected from any one of the species consisting of: any one of the microbes presented in Table 9; Table 10; Table 11 ; Table 12; Table 13; Table 14; Table 15; Table 16; or any combination, subgroup or multitude thereof; and wherein composition further does not comprise a different microbe or plurality of microbes selected from any one of the species, strains or isolates consisting of: any one of the microbes presented in Table 9; Table 10; Table 11 ; Table 12; Table 13; Table 14; Table 15; Table 16; or any combination, subgroup or multitude thereof.

[0108] In some embodiments, the microbe or plurality of microbes is a species or strain and is responsible for a metabolic pathway, wherein the metabolic pathway is selected from any one of the groups consisting of: a. carbohydrate metabolism, including; glycolysis I gluconeogenesis, the citrate cycle, the pentose phosphate pathway, fructose and mannose metabolism, galactose metabolism, ascorbate and aldarate metabolism, starch and sucrose metabolism, inositol phosphate metabolism, and pyruvate metabolism; b. lipid metabolism, including; fatty acid biosynthesis, fatty acid degradation, steroid biosynthesis and bile acid biosynthesis; c. amino acid metabolism; arginine biosynthesis, alanine, aspartate, and glutamate metabolism, glycine, serine and threonine metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis, lysine biosynthesis and degradation, arginine and proline metabolism, histidine metabolism, tyrosine metabolism, phenylalanine metabolism, tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, beta-alanine metabolism, taurine and hypotaurine metabolism, glutathione metabolism; andd. vitamin I co-factor metabolism, including; riboflavin metabolism, thiamine metabolism, vitamin b6 metabolism, nicotinate and nicotinamide metabolism, pantothenate biosynthesis, biotin metabolism, lipoic acid metabolism, folate biosynthesis, atrazine degradation, retinol metabolism, porphyrin metabolism, and carotenoid biosynthesis; and any combination or multitude thereof.

[0109] In some embodiments, the microbe is a species or strain which contains sulfur metabolic genes, wherein the sulfur metabolic genes are selected from the group consisting of: the sulfur metabolic genes presented in Table 37; and any combination or multitude thereof.

[0110] In some embodiments, the microbe is a species or strain which has a reaction / metabolite selected from the group consisting of: the reaction / metabolite presented in Table 37; and any combination or multitude thereof.

[0111] In some embodiments, the microbe is a species or strain which contains acetate metabolic genes, wherein the acetate metabolic genes are selected from the group consisting of: the acetate metabolic genes presented in Table 38; and any combination, subgroup or multitude thereof.

[0112] In some embodiments, the microbe is a species or strain which contains butyrate metabolic genes, wherein the butyrate metabolic genes are selected from the group consisting of: the butyrate metabolic genes presented in Table 39; and any combination, subgroup or multitude thereof.

[0113] In some embodiments, the microbe is a species or strain responsible for a metabolic pathway, wherein the metabolic pathway is selected from the group consisting of: the metabolic pathway categories presented in Table 40; and any combination, subgroup or multitude thereof.

[0114] In some embodiments, the microbe is a species or strain comprising a gene that is responsible for a phenotype selected from the group consisting of: reducing endogenous sulfide levels in the colon of a patient in need thereof; sulfide consumption; reducing sulfide and nitric oxide load on epithelial cells which affects cellular respiration leading to a metabolic lesion; reducing relative abundance and or metabolic activity of sulfidogenic microbiota; reducing sulfide levels in the colon directly through consumption / assimilation; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by metabolic substrate competition; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by diverting metabolic substrates away from the production of sulfide; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by consuming H2; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota by reducing release of metabolizable sulfur substrates; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota by reducing sulfur amino acid release (methionine, cysteine, homocysteine and / or taurine) into the colon; reducing colonic protein fermentation; reducingnitric oxide production in the colon; reducing nitric oxide levels in the colon; and inducing colonocyte apoptosis in lesions to break an induced stable inflammatory state.

[0115] In some embodiments, certain strains in the co-culture and / or formulation for administration to a subject are selected based on these phenotypes.

[0116] In some embodiments, the composition demonstrates a property selected from any one of the groups consisting of: a. emergent metabolic functions; b. emergent metabolic functions relating to: short-chain fatty acids (SCFAs); sulfide homeostasis; energy harvest; tryptophan metabolism; bile acid metabolism; vitamin production; and / or drug metabolism; c. synergistic metabolic functions and wherein the metabolic function of the consortium as a whole is greater than metabolic function of any of the individual isolates; d. synergistic metabolic functions and wherein the sulfide reduction metabolic function of the consortium as a whole is greater than sulfide reduction metabolic function of each of the individual isolates; e. synergistic metabolic functions and wherein the sulfide reduction metabolic function of the consortium as a whole is greater than the sulfide reduction metabolic function of each of the individual isolates (and wherein the sulfide reduction metabolic function is selected from the group consisting of: microbial competition for metabolic substrates (such as volatile fatty acids (acetate, propionate, butyrate), organic acids (lactate, valerate, succinate, pyruvate), amino acids (alanine, glutamate, serine) and ethanol as electron donors in cellular respiration); reduced sulfur substrate release in the colon; removing sulfide from the colon (such as assimilation of sulfide to cysteine)); f. synergistic metabolic functions relating to: short-chain fatty acids (SCFAs); sulfide homeostasis; energy harvest; tryptophan metabolism; bile acid metabolism; vitamin production; drug metabolism; g. reduces sulfide and nitric oxide load on epithelial cells which leads to a metabolic lesion via inhibition of cellular respiration; h. reduces relative abundance and or metabolic activity of sulfidogenic microbiota in vitro; i. reduces sulfide levels in vitro either directly or indirectly through consumption / assimilation of sulfide or metabolic substrates and / or a reduction in the production of sulfide; j. reduces sulfide levels in vitro via metabolic substrate competition; k. reduces sulfide levels in vitro by consuming hydrogen; l. reduces relative abundance and or metabolic activity of sulfidogenic microbiota; m. reduces sulfide levels in the colon either directly or indirectly through consumption / assimilation of sulfide or metabolic substrates and / or a reduction in theproduction of sulfide; reduce sulfide levels in the colon via metabolic substrate competition; and or reduce sulfide levels in the colon by consuming hydrogen; n. reduces the relative abundance and or metabolic activity of sulfidogenic microbiota by reducing metabolizable sulfur substrates; reduce sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing protein fermentation; o. induces colonocyte apoptosis in lesions to break an induced stable inflammatory state driven; p. drives down undesired inflammation; q. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host protease activity; r. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host protease activity; s. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial protease activity; t. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing microbial protease activity; u. reduces sulfide production in the colon by modulating host protease activity; v. reduces sulfide production in the colon by reducing host protease activity; w. reduces sulfide production in the colon by modulating microbial protease activity; x. reduces sulfide production in the colon by reducing microbial protease activity; y. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host antiprotease (protease inhibitor) activity; z. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host antiprotease (protease inhibitor) activity; aa. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial antiprotease (protease inhibitor) activity; ab. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) ac. into the colon by reducing microbial antiprotease (protease inhibitor) activity; ad. reduces sulfide production in the colon by modulating host antiprotease (protease inhibitor) activity; ae. reduces sulfide production in the colon by reducing host antiprotease (protease inhibitor) activity; af. reduces sulfide production in the colon by modulating microbial antiprotease (protease inhibitor) activity; ag. reduces sulfide production in the colon by reducing microbial antiprotease (protease inhibitor) activity;ah. prevents or reduces activation of the mucosa immune system in a natural killer T-cell driven IL-13 and IL-5 dependent, TH2 mediated, immune response; ai. decreases inflammation in the subject; aj. decreases inflammation in the subject when measured by a parameter selected from the group consisting of: TNFo signaling via NF-KB; I FNO signaling; IFNy signaling; IL6 JAK STAT3 signaling; activation of pro-apoptotic pathways; initiation of unfolded protein response; ak. down regulates genes associated with pro-apoptotic pathways and the unfolded protein response, including genes selected from the group consisting of: CHAC1 , CEBPB, TRIB3, PPP1 R15A, DDIT3, ATF4 and XBP1 ; al. treats and / or prevents dysbiosis; am. treats or prevents a medical disorder or disease associated with dysbiosis; an. treats or prevents a medical disorder or disease associated with mycobiome dysbiosis; ao. treats and / or prevents a gastrointestinal disorder; ap. treats and / or prevents a gastrointestinal disorder; wherein the gastrointestinal disorder is selected from the group consisting of: irritable bowel syndrome; an ulcer of the gastrointestinal tract; a cancer of the gastrointestinal tract; aq. treats and / or prevents gastrointestinal tract mucosal inflammation; ar. treats and / or prevents gastrointestinal tract mucosal inflammation, wherein the inflammation is associated with one or more of disorders selected from the group consisting of: inflammatory bowel disease (IBD), pouchitis, irritable bowel syndrome (IBS), an enteric bacterial infection, a metabolic disease, a neuropsychiatric disorder, an autoimmune disease, an allergic disorder, hepatic encephalopathy, or a cancer; as. treats and / or prevents inflammatory bowel disease; at. treats and / or prevents ulcerative colitis; Crohn's disease; gastroenteritis; colitis; checkpoint inhibitor colitis; and pouchitis; au. treats and / or prevents one or more of diseases or disorders selected from the group consisting of: liver disorders; metabolic disorders; neurological disorders; oncology disorders; cardiovascular disorders; immunological disorders; allergy; allergic and atopic disorders; infectious disease; and can affect the efficacy of cancer therapies. In some embodiments, the liver disorder is selected from the group consisting of: Primary sclerosing cholangitis; Non-alcoholic steatohepatitis; Non-alcoholic fatty liver disease; Alcoholic hepatitis; and Hepatic encephalopathy. In some embodiments, the metabolic disorder is selected from the group consisting of: Obesity; Insulin resistance; and Type 2 diabetes. In some embodiments, the neurological disorder is selected from the group consisting of: Autism; Multiple sclerosis; Parkinson’s disease; Depression; Anxiety; Bipolar disorder; Schizophrenia; and Mental health. In some embodiments, the oncology disorder is selected from the groupconsisting of: Melanoma; Renal cell carcinoma; Bowel cancer and precancerous polyps; Lymphoma; Leukaemia; Myeloma; Pancreatic cancer; Breast cancer; Lung cancer; Testicular cancer; and Sarcoma. In some embodiments, the cardiovascular disorder is selected from the group consisting of: Dyslipidaemia; Atherosclerotic heart disease; and Hypertension. In some embodiments, the immunological disorder is selected from the group consisting of: Type 1 diabetes; Rheumatoid arthritis; Psoriatic arthritis; Psoriasis; Systemic Lupus Erythematous; and Sjogren’s disease. In some embodiments, the allergic or atopic disorder is selected from the group consisting of: Food allergy; Anaphylaxis; Atopic dermatitis; and Atopic rhinitis or sinusitis. In some embodiments, the infectious disease is selected from the group consisting of: Clostridioides difficile infection; Multidrug resistant infection or colonisation; Renal tract or urinary tract infections; Blood stream infections; Respiratory infections; and Sepsis. In some embodiments, the disease or disorder is associated with mycobiome dysbiosis; and In some embodiments, the disease or disorder is associated with dysbiosis; av. increases the relative abundance of a member of the bacteria genus or colonizes a member of the bacteria genus selected from the group consisting of: Acidaminococcaceae (family), Acidaminococcus, Adlercreutzia, Agathobaculum, Akkermansia, Alistipes, Alterilei bacterium, Amedibacillus, Amedibacterium, Aminipila, Anaerobutyricum, Anaerococcus, Anaerocolumna, Anaerofustis, Anaerostipes, Anaerotignum, Anaerotruncus, Bacillus, Bacteroides, Barnesiella, Bifidobacterium, Bilophila, Blautia, Butyricimonas, Butyrivibrio, Campylobacter, Caproicibacter, Caproicibacterium, Caproiciproducens, Casaltella, Catenibacterium, Christensenella, Clostridium, Collinsella, Coprobacillus, Coprobacter, Coprococcus, Desulfovibrio, Dorea, Duodenibacillus, Dysosmobacter, Eggerthella, Enorma, Enterocl oster, Enterococcus, Escherichia, Ethanoligenens, Eubacterium, Faecalibacillus, Faecalibacterium, Faecalibaculum, Finegoldia, Flavonifractor, Flintibacter, Fusicatenibacter, Gemmiger, Gordonibacter, Granulicatella, Herbinix, Holdemanella, Holdemania, Hoylesella, Hungatella, Intestinibacter, Intestinibaculum, Intestinimonas, Lachnoanaerobaculum, Lachnoclostridium, Lachnospira, Lachnospiraceae incertae sedis (unclassified rank, Lachnospiraceae family), Lacrimispora, Lactococcus, Ligilactobacillus, Longibaculum, Longicatena, Mageeibacillus, Maliibacterium, Marvinbryantia, Massilimicrobiota, Massiliprevotella, Massilistercora, Mediterraneibacter, Megamonas, Megasphaera, Merdibacter, Mesosutterella, Mitsuokella, Mogi bacterium, Muribaculum, Negativibacillus, Novisyntrophococcus, Odoribacter, Olsenella, Oscillibacter, Oscillospiraceae (family), Oscillospiraceae incertae sedis (unclassified rank, Oscillospiraceae family), Parabacteroides, Paraclostridium, Paraprevotella, Parolsenella, Peptacetobacter, Peptoniphilus, Peptostreptococcus, Phascolarctobacterium, Phocaeicola, Porphyromonas, Prevotella, Pseudobutyrivibrio, Pusillibacter, Romboutsia, Roseburia, Ruminiclostridium, Ruminococcus, Ruthenibacterium, Schaalia, Segatella, Selenomonas, Sellimonas, Senegalimassilia, Slackia, Sodaliphilus, Solibaculum, Streptococcus, Subdoligranulum,Thomasclavelia, Tyzzerella, Veillonella and Vescimonas or any combination, subgroup or multitude thereof; aw. reduces the relative abundance of a member of the bacteria genus or decolonises a member of the bacteria genus selected from the group consisting of: Achromobacter, Acidaminococcus, Aeromonas, Alicyclobacillus, Bacteroides, Bifidobacterium, Blautia, Bosea, Burkholderiales, Clostridium, Cutibacterium, Desulfovibrio, Eggerthella, Enterobacter, Enterococcus, Escherichia, Eubacterium, Flavonifractor, Granulicatella, Hungatella, Klebsiella, Ligilactobacillus, Mediterraneibacter, Minicystis, Oscillibacter, Parabacteroides, Pluralibacter, Prevotella, Prosthecochloris, Pseudomonas, Rhodococcus, Salmonella, Schaalia, Serratia, Shewanella, Staphylococcus, Streptomyces, Sutterella, Veillonella, or any combination, subgroup or multitude thereof; and any combination or multitude thereof; and ax. treats or prevents ulcerative colitis, inflammatory bowel disease, Crohn’s disease, checkpoint inhibitor colitis, as well as other gastrointestinal diseases and symptoms, liver disorders, including, for example, primary sclerosing cholangitis, non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, alcoholic hepatitis, or hepatic encephalopathy, metabolic disorders, including, for example, obesity, insulin resistance, or type 2 diabetes, oncology indications, including, for example, melanoma, renal cell carcinoma, bowel cancer and precancerous polyps, lymphoma, leukemia, myeloma, pancreatic cancer, breast cancer, lung cancer, testicular cancer, or sarcoma, cardiovascular disorders, including, for example, dyslipidaemia, atherosclerotic heart disease, or hypertension, immunological diseases, including, for example, type 1 diabetes, rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematous, or Sjogren’s disease, allergic and atopic disorders, including, for example, food allergy, anaphylaxis, atopic dermatitis, or atopic rhinitis or sinusitis, infectious diseases, including, for example, Clostridioides difficile infection, multidrug resistant infection or colonisation, renal tract or urinary tract infections, blood stream infections, respiratory infections, or sepsis, neurological disorders, including for example, autism, multiple sclerosis, Parkinson’s disease, depression, anxiety, bipolar disorder, or schizophrenia.

[0117] In some embodiments, certain strains in the co-culture and / or formulation for administration to a subject are selected based on these properties.

[0118] In some embodiments, in combination with a therapy or active agent specific to the one or more diseases or disorders.

[0119] In some embodiments, the microbe is a fecal or colonic bacteria.

[0120] In some embodiments, the microbe is non-inflammatory.

[0121] In some embodiments, the microbe is cultured from a fecal or colonic biopsy sample.

[0122] In some embodiments, the microbial consortium comprises a community of microbes derived from a stool or biopsy of one or more human donors.

[0123] In some embodiments, the human donor is a healthy donor.

[0124] In some embodiments, the human donor is not an un-healthy donor.

[0125] In some embodiments, the human donor is not a donor presenting the underlying disease state.

[0126] In some embodiments, the community of microbes is not an inoculum.

[0127] In some embodiments, the community of microbes is cultured microbes produced from a bioreactor.

[0128] In some embodiments, the community of microbes is cultured microbes produced from a single bioreactor.

[0129] In some embodiments, the community of microbes is cultured microbes produced from a single continuous bioreactor.

[0130] In some embodiments, the community of microbes is cultured microbes produced from 1 to 10 bioreactors.

[0131] In some embodiments, the community of microbes is cultured from any number of bioreactors between and including 1 to 10, wherein the number is selected from the group consisting of: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10.

[0132] In some embodiments, the community of microbes is cultured microbes produced from 1 to 10 continuous bioreactors.

[0133] In some embodiments, the community of microbes is cultured from any number of continuous bioreactors between and including 1 to 10, wherein the number is selected from the group consisting of: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10.

[0134] In some embodiments, the community of microbes has a metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation.

[0135] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes the production and metabolism of short-chain fatty acids (SCFAs), including but not limited to acetate, propionate, and butyrate.

[0136] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes the synthesis and metabolism of gases such as hydrogen (H2), carbon dioxide (CO2) and methane (CH4) and may include hydrogen sulfide (H2S).

[0137] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes the synthesis and metabolism of organic acids such as lactate and succinate.

[0138] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes the deamination of amino acids, alongside biogenic amines such as putrescine, cadaverine, and histamine.

[0139] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes the production and metabolism of ethanol, ammonia, and indole.

[0140] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes carbohydrate metabolism into monosaccharides and oligosaccharides.

[0141] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes metabolism of monosaccharides and oligosaccharides.

[0142] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes the synthesis and metabolism of vitamins, particularly B-vitamins.

[0143] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes metabolism of monosaccharides and oligosaccharides.

[0144] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes the generation and metabolism of other metabolites and by-products, including but not limited to aromatic compounds, fatty alcohols, or ketones.

[0145] In some embodiments, the metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation includes a change in pH of the culture medium.

[0146] In some embodiments, the community of microbes has a total cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation.

[0147] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is from 0.1 to 100.0. For example, a cell count OD selected from the group consisting of: 0.1 ; 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1.0; 1.1 ; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2.0; 2.1 ; 2.2; 2.3; 2.4; 2.5; 2.6; 2.7; 2.8;2.9; 3.0; 3.1 ; 3.2; 3.3; 3.4; 3.5; 3.6; 3.7; 3.8; 3.9; 4.0; 4.1 ; 4.2; 4.3; 4.4; 4.5; 4.6; 4.7; 4.8; 4.9;5.0; 5.1 ; 5.2; 5.3; 5.4; 5.5; 5.6; 5.7; 5.8; 5.9; 6.0; 6.1 ; 6.2; 6.3; 6.4; 6.5; 6.6; 6.7; 6.8; 6.9; 7.0;7.1 ; 7.2; 7.3; 7.4; 7.5; 7.6; 7.7; 7.8; 7.9; 8.0; 8.1 ; 8.2; 8.3; 8.4; 8.5; 8.6; 8.7; 8.8; 8.9; 9.0; 9.1 ;9.2; 9.3; 9.4; 9.5; 9.6; 9.7; 9.8; 9.9; 10.0; 10.1 ; 10.2; 10.3; 10.4; 10.5; 10.6; 10.7; 10.8; 10.9; 11.0; 11.1 ; 11.2; 11.3; 11.4; 11.5; 11.6; 11.7; 11.8; 11.9; 12.0; 12.1 ; 12.2; 12.3; 12.4; 12.5;12.6; 12.7; 12.8; 12.9; 13.0; 13.1 ; 13.2; 13.3; 13.4; 13.5; 13.6; 13.7; 13.8; 13.9; 14.0; 14.1 ;14.2; 14.3; 14.4; 14.5; 14.6; 14.7; 14.8; 14.9; 15.0; 15.1 ; 15.2; 15.3; 15.4; 15.5; 15.6; 15.7;15.8; 15.9; 16.0; 16.1 ; 16.2; 16.3; 16.4; 16.5; 16.6; 16.7; 16.8; 16.9; 17.0; 17.1 ; 17.2; 17.3;17.4; 17.5; 17.6; 17.7; 17.8; 17.9; 18.0; 18.1 ; 18.2; 18.3; 18.4; 18.5; 18.6; 18.7; 18.8; 18.9;19.0; 19.1 ; 19.2; 19.3; 19.4; 19.5; 19.6; 19.7; 19.8; 19.9; 20.0; 20.1 ; 20.2; 20.3; 20.4; 20.5;20.6; 20.7; 20.8; 20.9; 21.0; 21.1 ; 21.2; 21.3; 21.4; 21.5; 21.6; 21.7; 21.8; 21.9; 22.0; 22.1 ;22.2; 22.3; 22.4; 22.5; 22.6; 22.7; 22.8; 22.9; 23.0; 23.1 ; 23.2; 23.3; 23.4; 23.5; 23.6; 23.7;23.8; 23.9; 24.0; 24.1 ; 24.2; 24.3; 24.4; 24.5; 24.6; 24.7; 24.8; 24.9; 25.0; 25.1 ; 25.2; 25.3;25.4; 25.5; 25.6; 25.7; 25.8; 25.9; 26.0; 26.1 ; 26.2; 26.3; 26.4; 26.5; 26.6; 26.7; 26.8; 26.9;27.0; 27.1 ; 27.2; 27.3; 27.4; 27.5; 27.6; 27.7; 27.8; 27.9; 28.0; 28.1 ; 28.2; 28.3; 28.4; 28.5;28.6; 28.7; 28.8; 28.9; 29.0; 29.1 ; 29.2; 29.3; 29.4; 29.5; 29.6; 29.7; 29.8; 29.9; 30.0; 30.1 ;30.2; 30.3; 30.4; 30.5; 30.6; 30.7; 30.8; 30.9; 31.0; 31.1 ; 31.2; 31.3; 31.4; 31.5; 31.6; 31.7;31.8; 31.9; 32.0; 32.1 ; 32.2; 32.3; 32.4; 32.5; 32.6; 32.7; 32.8; 32.9; 33.0; 33.1 ; 33.2; 33.3;33.4; 33.5; 33.6; 33.7; 33.8; 33.9; 34.0; 34.1 ; 34.2; 34.3; 34.4; 34.5; 34.6; 34.7; 34.8; 34.9;35.0; 35.1 ; 35.2; 35.3; 35.4; 35.5; 35.6; 35.7; 35.8; 35.9; 36.0; 36.1 ; 36.2; 36.3; 36.4; 36.5;36.6; 36.7; 36.8; 36.9; 37.0; 37.1 ; 37.2; 37.3; 37.4; 37.5; 37.6; 37.7; 37.8; 37.9; 38.0; 38.1 ;38.2; 38.3; 38.4; 38.5; 38.6; 38.7; 38.8; 38.9; 39.0; 39.1 ; 39.2; 39.3; 39.4; 39.5; 39.6; 39.7;39.8; 39.9; 40.0; 40.1 ; 40.2; 40.3; 40.4; 40.5; 40.6; 40.7; 40.8; 40.9; 41.0; 41.1 ; 41.2; 41.3;41.4; 41.5; 41.6; 41.7; 41.8; 41.9; 42.0; 42.1 ; 42.2; 42.3; 42.4; 42.5; 42.6; 42.7; 42.8; 42.9;43.0; 43.1 ; 43.2; 43.3; 43.4; 43.5; 43.6; 43.7; 43.8; 43.9; 44.0; 44.1 ; 44.2; 44.3; 44.4; 44.5;44.6; 44.7; 44.8; 44.9; 45.0; 45.1 ; 45.2; 45.3; 45.4; 45.5; 45.6; 45.7; 45.8; 45.9; 46.0; 46.1 ;46.2; 46.3; 46.4; 46.5; 46.6; 46.7; 46.8; 46.9; 47.0; 47.1 ; 47.2; 47.3; 47.4; 47.5; 47.6; 47.7;47.8; 47.9; 48.0; 48.1 ; 48.2; 48.3; 48.4; 48.5; 48.6; 48.7; 48.8; 48.9; 49.0; 49.1 ; 49.2; 49.3;49.4; 49.5; 49.6; 49.7; 49.8; 49.9; 50.0; 50.1 ; 50.2; 50.3; 50.4; 50.5; 50.6; 50.7; 50.8; 50.9;51.0; 51.1 ; 51.2; 51.3; 51.4; 51.5; 51.6; 51.7; 51.8; 51.9; 52.0; 52.1 ; 52.2; 52.3; 52.4; 52.5;52.6; 52.7; 52.8; 52.9; 53.0; 53.1 ; 53.2; 53.3; 53.4; 53.5; 53.6; 53.7; 53.8; 53.9; 54.0; 54.1 ;54.2; 54.3; 54.4; 54.5; 54.6; 54.7; 54.8; 54.9; 55.0; 55.1 ; 55.2; 55.3; 55.4; 55.5; 55.6; 55.7;55.8; 55.9; 56.0; 56.1 ; 56.2; 56.3; 56.4; 56.5; 56.6; 56.7; 56.8; 56.9; 57.0; 57.1 ; 57.2; 57.3;57.4; 57.5; 57.6; 57.7; 57.8; 57.9; 58.0; 58.1 ; 58.2; 58.3; 58.4; 58.5; 58.6; 58.7; 58.8; 58.9;59.0; 59.1 ; 59.2; 59.3; 59.4; 59.5; 59.6; 59.7; 59.8; 59.9; 60.0; 60.1 ; 60.2; 60.3; 60.4; 60.5;60.6; 60.7; 60.8; 60.9; 61.0; 61.1 ; 61.2; 61.3; 61.4; 61.5; 61.6; 61.7; 61.8; 61.9; 62.0; 62.1 ;62.2; 62.3; 62.4; 62.5; 62.6; 62.7; 62.8; 62.9; 63.0; 63.1 ; 63.2; 63.3; 63.4; 63.5; 63.6; 63.7;63.8; 63.9; 64.0; 64.1 ; 64.2; 64.3; 64.4; 64.5; 64.6; 64.7; 64.8; 64.9; 65.0; 65.1 ; 65.2; 65.3;65.4; 65.5; 65.6; 65.7; 65.8; 65.9; 66.0; 66.1 ; 66.2; 66.3; 66.4; 66.5; 66.6; 66.7; 66.8; 66.9;67.0; 67.1 ; 67.2; 67.3; 67.4; 67.5; 67.6; 67.7; 67.8; 67.9; 68.0; 68.1 ; 68.2; 68.3; 68.4; 68.5;68.6; 68.7; 68.8; 68.9; 69.0; 69.1 ; 69.2; 69.3; 69.4; 69.5; 69.6; 69.7; 69.8; 69.9; 70.0; 70.1 ;70.2; 70.3; 70.4; 70.5; 70.6; 70.7; 70.8; 70.9; 71.0; 71.1 ; 71.2; 71.3; 71.4; 71.5; 71.6; 71.7;71.8; 71.9; 72.0; 72.1 ; 72.2; 72.3; 72.4; 72.5; 72.6; 72.7; 72.8; 72.9; 73.0; 73.1 ; 73.2; 73.3;73.4; 73.5; 73.6; 73.7; 73.8; 73.9; 74.0; 74.1 ; 74.2; 74.3; 74.4; 74.5; 74.6; 74.7; 74.8; 74.9;75.0; 75.1 ; 75.2; 75.3; 75.4; 75.5; 75.6; 75.7; 75.8; 75.9; 76.0; 76.1 ; 76.2; 76.3; 76.4; 76.5;76.6; 76.7; 76.8; 76.9; 77.0; 77.1 ; 77.2; 77.3; 77.4; 77.5; 77.6; 77.7; 77.8; 77.9; 78.0; 78.1 ;78.2; 78.3; 78.4; 78.5; 78.6; 78.7; 78.8; 78.9; 79.0; 79.1 ; 79.2; 79.3; 79.4; 79.5; 79.6; 79.7;79.8; 79.9; 80.0; 80.1 ; 80.2; 80.3; 80.4; 80.5; 80.6; 80.7; 80.8; 80.9; 81.0; 81.1 ; 81.2; 81.3;81.4; 81.5; 81.6; 81.7; 81.8; 81.9; 82.0; 82.1 ; 82.2; 82.3; 82.4; 82.5; 82.6; 82.7; 82.8; 82.9;83.0; 83.1 ; 83.2; 83.3; 83.4; 83.5; 83.6; 83.7; 83.8; 83.9; 84.0; 84.1 ; 84.2; 84.3; 84.4; 84.5;84.6; 84.7; 84.8; 84.9; 85.0; 85.1 ; 85.2; 85.3; 85.4; 85.5; 85.6; 85.7; 85.8; 85.9; 86.0; 86.1 ;86.2; 86.3; 86.4; 86.5; 86.6; 86.7; 86.8; 86.9; 87.0; 87.1 ; 87.2; 87.3; 87.4; 87.5; 87.6; 87.7;87.8; 87.9; 88.0; 88.1 ; 88.2; 88.3; 88.4; 88.5; 88.6; 88.7; 88.8; 88.9; 89.0; 89.1 ; 89.2; 89.3;89.4; 89.5; 89.6; 89.7; 89.8; 89.9; 90.0; 90.1 ; 90.2; 90.3; 90.4; 90.5; 90.6; 90.7; 90.8; 90.9;91.0; 91.1 ; 91.2; 91.3; 91.4; 91.5; 91.6; 91.7; 91.8; 91.9; 92.0; 92.1 ; 92.2; 92.3; 92.4; 92.5;92.6; 92.7; 92.8; 92.9; 93.0; 93.1 ; 93.2; 93.3; 93.4; 93.5; 93.6; 93.7; 93.8; 93.9; 94.0; 94.1 ;94.2; 94.3; 94.4; 94.5; 94.6; 94.7; 94.8; 94.9; 95.0; 95.1 ; 95.2; 95.3; 95.4; 95.5; 95.6; 95.7;95.8; 95.9; 96.0; 96.1 ; 96.2; 96.3; 96.4; 96.5; 96.6; 96.7; 96.8; 96.9; 97.0; 97.1 ; 97.2; 97.3;97.4; 97.5; 97.6; 97.7; 97.8; 97.9; 98.0; 98.1 ; 98.2; 98.3; 98.4; 98.5; 98.6; 98.7; 98.8; 98.9;99.0; 99.1 ; 99.2; 99.3; 99.4; 99.5; 99.6; 99.7; 99.8; 99.9; and 100.0.

[0148] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is from 0.8 to 5.0.

[0149] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is preferably from 1.0 to 3.0.

[0150] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is from 1 .5 to 2.5.

[0151] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is from 2.0 to 4.0.

[0152] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is 5.0.

[0153] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is 0.8 to 1 .5.

[0154] In some embodiments, the cultured microbes are derived from multiple of human donors.

[0155] In some embodiments, the community of microbes comprises uncultured microbes.

[0156] In some embodiments, the uncultured microbes are derived from a single human donor.

[0157] In some embodiments, the composition is a fecal transplant microbiota composition.

[0158] In some embodiments, the community of microbes comprise microbes which lack lytic phage.

[0159] In some embodiments, the community of microbes comprises microbes which lack genes selected from the group consisting of: antimicrobial resistant genes encoding resistance to ESBL, tetracycline, efflux, erythromycin, macrolide, trimethoprim, beta-lactamase (not ESBL or carbapenemase), streptomycin, beta-lactamase (unknown spectrum), lincosamide,chloramphenicol, sulfonamide, other aminoglycoside resistance (non-RMT), gentamicin / kanamycin / tobramycin, lincosamide / macrolide / streptogramin, fosfomycin, carbapenemase (MBL), lincosamide / streptogramin, and vancomycin.

[0160] In some embodiments, the community comprises microbes which lack antimicrobial resistant genes, and the percentage of microbes of the total consortium which lack these genes (by isolate classification or by total cell count) is an “at least percentage” that is selected from the group consisting of: at least 99.9%; at least 99.5%; at least 99%; at least 98.5%; at least 98%; at least 97.5%; at least 97%; at least 96.5%; at least 96%; at least 95.5%; at least 95%; at least 94.5%; at least 94%; at least 93.5%; at least 93%; at least 92.5%; at least 92%; at least 91.5%; at least 91 %; at least 90.5%; at least 90%; at least 89.5%; at least 89%; at least 88.5%; at least 88%; at least 87.5%; at least 87%; at least 86.5%; at least 86%; at least 85.5%; at least 85%; at least 84.5%; at least 84%; at least 83.5%; at least 83%; at least 82.5%; at least 82%; at least 81.5%; at least 81%; at least 80.5%; at least 80%; at least 79.5%; at least 79%; at least 78.5%; at least 78%; at least 77.5%; at least 77%; at least 76.5%; at least 76%; at least 75.5%; at least 75%; at least 74.5%; at least 74%; at least 73.5%; at least 73%; at least 72.5%; at least 72%; at least 71.5%; at least 71%; at least 70.5%; at least 70%; at least 69.5%; at least 69%; at least 68.5%; at least 68%; at least 67.5%; at least 67%; at least 66.5%; at least 66%; at least 65.5%; at least 65%; at least 64.5%; at least 64%; at least 63.5%; at least 63%; at least 62.5%; at least 62%; at least 61.5%; at least 61%; at least 60.5%; at least 60%; at least 59.5%; at least 59%; at least 58.5%; at least 58%; at least 57.5%; at least 57%; at least 56.5%; at least 56%; at least 55.5%; at least 55%; at least 54.5%; at least 54%; at least 53.5%; at least 53%; at least 52.5%; at least 52%; at least 51.5%; at least 51 %; at least 50.5%; at least 50%; at least 49.5%; at least 49%; at least 48.5%; at least 48%; at least 47.5%; at least 47%; at least 46.5%; at least 46%; at least 45.5%; at least 45%; at least 44.5%; at least 44%; at least 43.5%; at least 43%; at least 42.5%; at least 42%; at least 41 .5%; at least 41 %; at least 40.5%; at least 40%; at least 39.5%; at least 39%; at least 38.5%; at least 38%; at least 37.5%; at least 37%; at least 36.5%; at least 36%; at least 35.5%; at least 35%; at least 34.5%; at least 34%; at least 33.5%; at least 33%; at least 32.5%; at least 32%; at least 31.5%; at least 31 %; at least 30.5%; at least 30%; at least 29.5%; at least 29%; at least 28.5%; at least 28%; at least 27.5%; at least 27%; at least 26.5%; at least 26%; at least 25.5%; at least 25%; at least 24.5%; at least 24%; at least 23.5%; at least 23%; at least 22.5%; at least 22%; at least 21.5%; at least 21 %; at least 20.5%; at least 20%; at least 19.5%; at least 19%; at least 18.5%; at least 18%; at least 17.5%; at least 17%; at least 16.5%; at least 16%; at least 15.5%; at least 15%; at least 14.5%; at least 14%; at least 13.5%; at least 13%; at least 12.5%; at least 12%; at least 11.5%; at least 11 %; at least 10.5%; at least 10%; and a value within a range defined by any two of the aforementioned values.

[0161] In some embodiments, the microbes are selected using the following criteria: lack antimicrobial resistant genes; and the percentage of microbes of the total consortium whichlack these genes (by isolate classification or by total cell count) is an “at least percentage” that is selected from the group consisting of: at least 99.9%; at least 99.5%; at least 99%; at least 98.5%; at least 98%; at least 97.5%; at least 97%; at least 96.5%; at least 96%; at least 95.5%; at least 95%; at least 94.5%; at least 94%; at least 93.5%; at least 93%; at least 92.5%; at least 92%; at least 91.5%; at least 91 %; at least 90.5%; at least 90%; at least 89.5%; at least 89%; at least 88.5%; at least 88%; at least 87.5%; at least 87%; at least 86.5%; at least 86%; at least 85.5%; at least 85%; at least 84.5%; at least 84%; at least 83.5%; at least 83%; at least 82.5%; at least 82%; at least 81.5%; at least 81%; at least 80.5%; at least 80%; at least 79.5%; at least 79%; at least 78.5%; at least 78%; at least 77.5%; at least 77%; at least 76.5%; at least 76%; at least 75.5%; at least 75%; at least 74.5%; at least 74%; at least 73.5%; at least 73%; at least 72.5%; at least 72%; at least 71.5%; at least 71%; at least 70.5%; at least 70%; at least 69.5%; at least 69%; at least 68.5%; at least 68%; at least 67.5%; at least 67%; at least 66.5%; at least 66%; at least 65.5%; at least 65%; at least 64.5%; at least 64%; at least 63.5%; at least 63%; at least 62.5%; at least 62%; at least 61.5%; at least 61%; at least 60.5%; at least 60%; at least 59.5%; at least 59%; at least 58.5%; at least 58%; at least 57.5%; at least 57%; at least 56.5%; at least 56%; at least 55.5%; at least 55%; at least 54.5%; at least 54%; at least 53.5%; at least 53%; at least 52.5%; at least 52%; at least 51.5%; at least 51 %; at least 50.5%; at least 50%; at least 49.5%; at least 49%; at least 48.5%; at least 48%; at least 47.5%; at least 47%; at least 46.5%; at least 46%; at least 45.5%; at least 45%; at least 44.5%; at least 44%; at least 43.5%; at least 43%; at least 42.5%; at least 42%; at least 41 .5%; at least 41 %; at least 40.5%; at least 40%; at least 39.5%; at least 39%; at least 38.5%; at least 38%; at least 37.5%; at least 37%; at least 36.5%; at least 36%; at least 35.5%; at least 35%; at least 34.5%; at least 34%; at least 33.5%; at least 33%; at least 32.5%; at least 32%; at least 31.5%; at least 31 %; at least 30.5%; at least 30%; at least 29.5%; at least 29%; at least 28.5%; at least 28%; at least 27.5%; at least 27%; at least 26.5%; at least 26%; at least 25.5%; at least 25%; at least 24.5%; at least 24%; at least 23.5%; at least 23%; at least 22.5%; at least 22%; at least 21.5%; at least 21 %; at least 20.5%; at least 20%; at least 19.5%; at least 19%; at least 18.5%; at least 18%; at least 17.5%; at least 17%; at least 16.5%; at least 16%; at least 15.5%; at least 15%; at least 14.5%; at least 14%; at least 13.5%; at least13%; at least 12.5%; at least 12%; at least 11.5%; at least 11 %; at least 10.5%; a at least 10% and a value within a range defined by any two of the aforementioned values.

[0162] In some embodiments, the composition is lyophilized.

[0163] In some embodiments, the composition is a liquid.

[0164] In some embodiments, after at least 4 weeks of storage at room temperature, said composition is capable of maintaining at least 50% cell viability relative to the initial cell viability immediately prior to storage.

[0165] In some embodiments, after at least 4 weeks of storage at room temperature, said composition is capable of maintaining a cell viability relative to the initial cell viabilityimmediately prior to storage selected from the group consisting of: at least 99.9%; at least 99.5%; at least 99%; at least 98.5%; at least 98%; at least 97.5%; at least 97%; at least 96.5%; at least 96%; at least 95.5%; at least 95%; at least 94.5%; at least 94%; at least 93.5%; at least 93%; at least 92.5%; at least 92%; at least 91.5%; at least 91%; at least 90.5%; at least 90%; at least 89.5%; at least 89%; at least 88.5%; at least 88%; at least 87.5%; at least 87%; at least 86.5%; at least 86%; at least 85.5%; at least 85%; at least 84.5%; at least 84%; at least 83.5%; at least 83%; at least 82.5%; at least 82%; at least 81.5%; at least 81%; at least 80.5%; at least 80%; at least 79.5%; at least 79%; at least 78.5%; at least 78%; at least 77.5%; at least 77%; at least 76.5%; at least 76%; at least 75.5%; at least 75%; at least 74.5%; at least 74%; at least 73.5%; at least 73%; at least 72.5%; at least 72%; at least 71.5%; at least 71 %; at least 70.5%; at least 70%; at least 69.5%; at least 69%; at least 68.5%; at least 68%; at least 67.5%; at least 67%; at least 66.5%; at least 66%; at least 65.5%; at least 65%; at least 64.5%; at least 64%; at least 63.5%; at least 63%; at least 62.5%; at least 62%; at least 61 .5%; at least 61 %; at least 60.5%; at least 60%; at least 59.5%; at least 59%; at least 58.5%; at least 58%; at least 57.5%; at least 57%; at least 56.5%; at least 56%; at least 55.5%; at least 55%; at least 54.5%; at least 54%; at least 53.5%; at least 53%; at least 52.5%; at least 52%; at least 51.5%; at least 51 %; at least 50.5%; at least 50%; at least 49.5%; at least 49%; at least 48.5%; at least 48%; at least 47.5%; at least 47%; at least 46.5%; at least 46%; at least 45.5%; at least 45%; at least 44.5%; at least 44%; at least 43.5%; at least 43%; at least 42.5%; at least 42%; at least 41.5%; at least 41 %; at least 40.5%; at least 40%; at least 39.5%; at least 39%; at least 38.5%; at least 38%; at least 37.5%; at least 37%; at least 36.5%; at least 36%; at least 35.5%; at least 35%; at least 34.5%; at least 34%; at least 33.5%; at least 33%; at least 32.5%; at least 32%; at least 31.5%; at least 31 %; at least 30.5%; at least 30%; at least 29.5%; at least 29%; at least 28.5%; at least 28%; at least 27.5%; at least 27%; at least 26.5%; at least 26%; at least 25.5%; at least 25%; at least 24.5%; at least 24%; at least 23.5%; at least 23%; at least 22.5%; at least 22%; at least 21.5%; at least 21%; at least 20.5%; at least 20%; at least 19.5%; at least 19%; at least 18.5%; at least 18%; at least 17.5%; at least 17%; at least 16.5%; at least 16%; at least 15.5%; at least 15%; at least 14.5%; at least 14%; at least 13.5%; at least 13%; at least 12.5%; at least 12%; at least 11.5%; at least 11%; at least 10.5%; at least 10%; and a value within a range defined by any two of the aforementioned values.

[0166] In some embodiments, after at least 4 weeks of storage at room temperature said composition is capable of maintaining about 60% to about 80% cell viability relative to the initial cell viability immediately prior to the start of said storage.

[0167] In some embodiments, the composition comprises a prebiotic.

[0168] In some embodiments, the composition comprises a carrier.

[0169] In some embodiments, the composition comprises an insoluble fibre, a buffer, an osmotic agent, an antifoaming agent, and / or a preservative. For example, a fibre source maybe added to a composition of the disclosure. Exemplary fibre is selected from the group consisting of: Inulin, resistant starch, pectin, cellulose, hemicellulose, xylan, arabinan, p- glucans, fructooligosaccharides (FOS), galactooligosaccharides (GOS), mannan, chitin, lignin-associated polysaccharides, and polydextrose, oligofructose, fructooligosaccharides (FOS), and fructans from sources like agave, Jerusalem artichoke, and chicory root; resistant starches of various types (RS1-RS4); pectins, both high and low methoxyl; gums such as guar gum, locust bean gum, xanthan gum, gum arabic, and psyllium husk; other polysaccharides like arabinogalactan and dextran; lignin-associated polysaccharides; and specific examples like konjac mannan and okra gum.

[0170] In some embodiments, the composition comprises a chemostat medium.

[0171] In some embodiments, the composition comprises a saline composition.

[0172] In some embodiments, the composition comprises a resistant starch.

[0173] In some embodiments, the composition is lyophilized with pharmaceutically acceptable excipients.

[0174] In some embodiments, the composition comprises a stabiliser and / or cryoprotectant.

[0175] In some embodiments, such ingredients (e.g., agents, materials, etc.) are included in the co-culture, the formulation for administration to a subject, or both according to several embodiments. Such ingredients may be natural or non-naturally occurring (e.g., partially or fully modified, synthetic, etc.).

[0176] In some embodiments, the cryoprotectant is selected from the group consisting of: trehalose; inulin; maltodextrin; mannitol; sucrose; glycerol; sorbitol; DMSO; propylene glycol; ethylene glycol; saccharose; galactose-lactose; cylodextrins inclusive ofhydroxypropyl-p- cyclodextrin, methyl-p-cyclodextrin, sulfobutyl ether-p-cyclodextrin, alpha-cyclodextrin and gamma-cyclodextrin and any combination or multitude thereof.

[0177] In some embodiments, said cryoprotectant further comprises a compound selected from the group consisting of: glycerol; polyethylene glycol (PEG); glycerine; erythritol; arabitol; xylitol; sorbitol; glucose; lactose; ribose; classes of antioxidants; oxygen reducers; and any combination or multitude thereof.

[0178] In some embodiments, said cryoprotectant is trehalose at a concentration of 2% to 15% (e.g., 2-6%, 6-12%, 10-15%, and overlapping ranges therein) in said lyophilized formulation.

[0179] In some embodiments, said cryoprotectant is inulin at a concentration of 2% to 15% (e.g., 2-6%, 6-12%, 10-15%, and overlapping ranges therein) in said lyophilized formulation.

[0180] In some embodiments, said cryoprotectant is maltodextrin at a concentration of 2% to 15% (e.g., 2-6%, 6-12%, 10-15%, and overlapping ranges therein) in said lyophilized formulation.

[0181] In some embodiments, said cryoprotectant is trehalose at a concentration of at least 5% in said lyophilized formulation.

[0182] In some embodiments, said cryoprotectant is trehalose at a concentration of at least 10% in said lyophilized formulation.

[0183] In some embodiments, said composition is a pharmaceutical composition.

[0184] In some embodiments, the at least one strain of bacteria is diluted with an inert powdered diluent.

[0185] In some embodiments, said composition comprises one or more pharmaceutically acceptable carriers or excipients.

[0186] In some embodiments, said composition is formulated as a geltab, pill, enema, microcapsule, capsule, powder, caplet, or tablet.

[0187] In some embodiments, the capsule or tablet is enteric- coated, pH dependent, slow-release, and / or gastro-resistant.

[0188] In some embodiments, the composition is adapted for administration orally, colonically or rectally.

[0189] In some embodiments, every 200 mg of the composition comprises a pharmacologically active dose of bacteria cells or spores selected from the group consisting of: 103to 1014; 104to 1014; 105to 1014; 106to 1014; 107to 1014; 108to 1014; 104to 1013; 105to 1012; 106to 1011; 107to 1010; 108to 109; 103to 1013; 103to 1012; 103to 1011; 103to 1010; 103to 109; 103to 108; 103to 107; 103to 106; 103to 105; 103to 104colony forming units (cfu) or total cell count; and a value within a range defined by any two of the aforementioned values.

[0190] In some embodiments, the composition comprises a pharmacologically active dose of bacteria cells or spores selected from the group consisting of: from 100 cfu / mL to 100 billion cfu / mL, from 1000 cfu / mL to 10,000 cfu / mL, from 100,000 cfu / mL to 100 billion cfu / mL, from 1 million cfu / mL to 100 billion cfu / mL, from 10 million cfu / mL to 100 billion cfu / mL, from 10 million to 50 million cfu / mL, more preferably from 50 million to 100 million cfu / mL, from 100 million to 500 million cfu / mL, from 500 million to 1 billion cfu / mL, from 1 billion to 5 billion cfu / mL, from 5 billion to 10 billion cfu / mL, from 10 billion to 15 billion cfu / mL, from 15 billion to 20 billion cfu / mL, from 20 billion to 25 billion cfu / mL, from 25 billion to 30 billion cfu / mL, from 30 billion to 35 billion cfu / mL, from 35 billion to 40 billion cfu / mL, from 40 billion to 45 billion cfu / mL, from 45 billion to 50 billion cfu / mL, from 50 billion to 55 billion cfu / mL, from 55 billion to 60 billion cfu / mL, from 60 billion to 65 billion cfu / mL, from 65 billion to 70 billion cfu / mL, from 70 billion to 75 billion cfu / mL, from 75 billion to 80 billion cfu / mL, from 80 billion to 85 billion cfu / mL, from 85 billion to 90 billion cfu / mL, from 90 billion to 95 billion cfu / mL, from 95 billion to 100 billion cfu / mL and a value within a range defined by any two of the aforementioned values.

[0191] In some embodiments, a single dosage form, such as a single capsule, tablet, pill, or powder, includes an amount of bacterial cells ranging from: 100 cfu per dosage form to 100billion cfu per dosage form, 1000 cfu per dosage form to 10,000 cfu per dosage form, 100,000 cfu per dosage form to 100 billion cfu per dosage form, 1 million cfu per dosage form to 100 billion cfu per dosage forml million cfu per dosage form to 100 billion cfu per dosage form, such as 1 million to 50 million cfu per dosage form, 50 million to 100 million cfu per dosage form, 100 million to 500 million cfu per dosage form, 500 million to 1 billion cfu per dosage form, 1 billion to 5 billion cfu per dosage form, 5 billion to 10 billion cfu per dosage form, 10 billion to 15 billion cfu per dosage form, 15 billion to 20 billion cfu per dosage form, 20 billion to 25 billion cfu per dosage form, 25 billion to 30 billion cfu per dosage form, 30 billion to 35 billion cfu per dosage form, 35 billion to 40 billion cfu per dosage form, 40 billion to 45 billion cfu per dosage form, 45 billion to 50 billion cfu per dosage form, 50 billion to 55 billion cfu per dosage form, 55 billion to 60 billion cfu per dosage form, 60 billion to 65 billion cfu per dosage form, 65 billion to 70 billion cfu per dosage form, 70 billion to 75 billion cfu per dosage form, 75 billion to 80 billion cfu per dosage form, 80 billion to 85 billion cfu per dosage form, 85 billion to 90 billion cfu per dosage form, 90 billion to 95 billion cfu per dosage form, 95 billion to 100 billion cfu per dosage form, or an amount within a range defined by any two of the aforementioned values.

[0192] In some embodiments, the dosage form is an amount ranging from about 50 mg to about 1000 mg, such as 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 mg, or an amount within a range defined by any two of the aforementioned values.

[0193] In some embodiments, the formulation or composition is administered as a single dosage form or as a multi-dosage form, such as 1 , 2, 3, 4, 5, or 6 or more dosages. In some embodiments, the formulations are administered once or multiple times daily, such as 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 times daily in single or multi-dosage form. In some embodiments, a daily dosage of the formulations are administered all at once or are spread out during a the day. In some embodiments, the formulations or compositions are administered hourly, or once every 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7, hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, or 5 years. In some embodiments, the formulations are administered over a period of 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, or more, or indefinitely. In some embodiments, the formulations are administered at various dosages and amounts at different periods or stages of health, including, for example, at higher dosages during an induction stage or at lower dosages during maintenance stage.

[0194] In some embodiments, the formulation or composition comprise a plurality of microbial species produced by co-culturing the plurality of microbial species in a single vessel, such as a bioreactor. In some embodiments, the co-culture of the plurality of microbial species includes an amount of bacterial cells ranging from 10 million cfu / mL to 100 billion cfu / mL, from 10 million to 50 million cfu / mL, from 50 million to 100 million cfu / mL, from 100 million to 500 million cfu / mL, from 500 million to 1 billion cfu / mL, from 1 billion to 5 billion cfu / mL, from 5 billion to 10 billion cfu / mL, from 10 billion to 15 billion cfu / mL, from 15 billion to 20 billion cfu / mL, from 20 billion to 25 billion cfu / mL, from 25 billion to 30 billion cfu / mL, from 30 billion to 35 billion cfu / mL, from 35 billion to 40 billion cfu / mL, from 40 billion to 45 billion cfu / mL, from 45 billion to 50 billion cfu / mL, from 50 billion to 55 billion cfu / mL, from 55 billion to 60 billion cfu / mL, from 60 billion to 65 billion cfu / mL, from 65 billion to 70 billion cfu / mL, from 70 billion to 75 billion cfu / mL, from 75 billion to 80 billion cut / mL, from 80 billion to 85 billion cfu / mL, from 85 billion to 90 billion cfu / mL, from 90 billion to 95 billion cfu / mL, or from 95 billion to 100 billion cfu / mL, or a range within any of the aforementioned values. In some embodiments, the vessel or bioreactor has a capacity ranging from about 1 mL to about 10,000,000 L, such as 1 mL, 5 mL, 10 mL, 100 mL, 0.5 L, 1 L, 2 L, 3 L, 4 L, 5 L, 10 L, 20 L, 50 L, 100 L, 500 L, 1000 L, 2000 L, 3000 L, 4000 L, 5000 L, 6000 L, 7000 L, 8000 L, 9000 L, 10,000 L, , 20,000 L, 30,000 L, 40,000 L, 50,000 L, 60,000 L, 70,000 L, 80,000 L, 90,000 L, 100,000 L, 150,000 L, 200,000 L, 300,000 L, 400,000 L, 500,000 L, 600,000 L, 700,000 L, 800,000 L, 900,000 L, 1 ,000,000 L, 1 ,500,000 L, 2,000,000 L, 2,500,000 L, 3,000,000 L, 4,000,000 L, 5,000,000 L, 6,000,000 L, 7,000,000 L, 8,000,000 L, 9,000,000 L, or 10,000,000 L. or an amount within a range defined by any two of the aforementioned values.

[0195] In some embodiments, a single formulation (provided for example in a capsule, tablet, powder, or other oral formulation) is capable of treating a particular disease amongst the population suffering from said disease.

[0196] In some embodiments, precision therapeutics are provided wherein the formulation is altered based on sex, ethnicity, disease sub-types, diet, age, etc.

[0197] In some embodiments, personalized formulations may also be provided that are individualized to a patient.

[0198] In some embodiments, the types and numbers of core community and keystone 10 strain are selected to deliver a therapeutically effective dose to a subject and / or for the treatment of a disease or its symptoms.

[0199] In some embodiments, other routes of administration may also be used (including but not limited to inhalation, rectal, vaginal, implants (e.g., on a scaffold or substrate), etc.).

[0200] In several embodiments, the types and numbers of core community and keystone strain are selected to deliver a therapeutically effective dose to a subject and / or for the treatment of a disease or its symptoms, such as, for example, ulcerative colitis, inflammatory bowel disease, Crohn’s disease, checkpoint inhibitor colitis, primary sclerosing cholangitis,non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, alcoholic hepatitis, hepatic encephalopathy, obesity, insulin resistance, type 2 diabetes, melanoma, renal cell carcinoma, bowel cancer and precancerous polyps, lymphoma, leukemia, myeloma, pancreatic cancer, breast cancer, lung cancer, testicular cancer, sarcoma, dyslipidaemia, atherosclerotic heart disease, hypertension, type 1 diabetes, rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematous, Sjogren’s disease, food allergy, anaphylaxis, atopic dermatitis, atopic rhinitis or sinusitis, clostridioides difficile infection, multidrug resistant infection or colonisation, renal tract or urinary tract infections, blood stream infections, respiratory infections, sepsis, autism, multiple sclerosis, Parkinson’s disease, depression, anxiety, bipolar disorder, or schizophrenia, or combinations thereof.

[0201] In some embodiments, the composition comprises a pharmacologically active dose of bacteria cells or spores wherein the concentration of the bacteria cells or spores as a dry microbial body, is selected from the group consisting of: between 5 to 50 w / w %, 1 to 75 w / w %, 0.1 to 100 w / w %, and 1 to 100 w / w %.

[0202] In other embodiments, compositions of the disclosure can be defined functionally by their capacity to maintain specific, measurable metabolic phenotypes over time and under certain challenge conditions. For example, this may include an assessment of a compositions ability to metabolise target metabolites (i.e. metabolic functional capacity) such as hydrogen sulphide, amino acids, or bile acids at or above a defined rate in the presence of standardised substrates or microbial challenges. In an example, such assessments may be undertaken with comparison to an appropriate control composition. In certain examples, metabolic functional capacity may also be defined by the number of unique Clusters of Orthologous Groups (COGs) identified in a compositions collective genome, providing a quantifiable measure of functional breadth that is independent of taxonomic composition. A key mechanism of action (MOA) for a composition may, in certain examples, be hydrogen sulphide (H2S) consumption, measured by the reduction of exogenous H2S levels during in vitro fermentation. Accordingly, in an example, compositions of the disclosure may be characterised based on capacity to reduce exogenous H2S levels during in vitro fermentation. For example, the composition may be an intermediate population of the disclosure or a drug product.

[0203] In some embodiments, the microbial consortium comprises: a plurality of active microbes and an effective amount of a supportive community of microbes, wherein the plurality of active microbes metabolize a first metabolic substrate to produce one or more than one metabolite, wherein the first metabolic substrate causes or contributes to disease in an animal, and the supportive community of microbes comprises between 1 and 1000 microbial strains, wherein for the supportive community of microbes, at least one of the following four conditions is met: 1) the supportive community of microbes metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metaboliteinhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, 2) the supportive community of microbes increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate, 3) the supportive community of microbes enhances one or more than one characteristic of the plurality of active microbes when administered to an animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes, and 4) the supportive community of microbes catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2- oxoglutarate, propionate, 1,3-propanediol, succinate, ethanol, lactate, butyrate, 2,3- butanediol, acetone, butanol, formate, H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2-methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3-(1 H-indol-3- yl)propanoate, 5-aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7- oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0204] In some embodiments, the microbial consortium: 1) metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metabolite inhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, and 2) increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate.

[0205] In some embodiments, the microbial consortium: 1) metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metabolite inhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, and 2) enhances one or more than one characteristic of the plurality of active microbes when administered to the animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes.

[0206] In some embodiments, the microbial consortium: 1) metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metabolite inhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, and 2) catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2-oxoglutarate, propionate, 1 ,3-propanediol, succinate, ethanol, lactate, butyrate, 2,3-butanediol, acetone, butanol, formate, H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2- methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3- (1 H-indol-3-yl)propanoate, 5-aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7-oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0207] In some embodiments, the microbial consortium: 1) increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate, and 2) enhances one or more than one characteristic of the plurality of active microbes when administered to the animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes.

[0208] In some embodiments, the microbial consortium: 1) increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate, and 2) catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2-oxoglutarate, propionate, 1 ,3-propanediol, succinate, ethanol, lactate, butyrate, 2,3-butanediol, acetone, butanol, formate, H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2- methyl butyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3- (1 H-indol-3-yl)propanoate, 5- aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 fromsuccinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7-oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0209] In some embodiments, the microbial consortium: 1) enhances one or more than one characteristic of the plurality of active microbes when administered to the animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes, and 2) catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2- oxoglutarate, propionate, 1,3-propanediol, succinate, ethanol, lactate, butyrate, 2,3- butanediol, acetone, butanol, formate, H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2- methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3- (1 H-indol-3- yljpropanoate, 5-aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7- oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0210] In some embodiments, the microbial consortium: 1) metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metabolite inhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, 2) increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate, and 3) enhances one or more than one characteristic of the plurality of active microbes when administered to an animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes.

[0211] In some embodiments, the microbial consortium: 1) increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts saidprecursor into a metabolite that is not the first metabolic substrate, and 2) enhances one or more than one characteristic of the plurality of active microbes when administered to an animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes, and 3) catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2- oxoglutarate, propionate, 1,3-propanediol, succinate, ethanol, lactate, butyrate, 2,3- butanediol, acetone, butanol, formate, H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2- methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3- (1 H-indol-3- yl)propanoate, 5-aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7- oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0212] In some embodiments, the microbial consortium: 1) metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metabolite inhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, 2) increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate, and 3) catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2-oxoglutarate, propionate, 1 ,3-propanediol, succinate, ethanol, lactate, butyrate, 2,3-butanediol, acetone, butanol, formate, H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2- methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3- (1 H-indol-3-yl)propanoate, 5-aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7-oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA),conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0213] In some embodiments, the microbial consortium: 1) metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metabolite inhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, 2) enhances one or more than one characteristic of the plurality of active microbes when administered to an animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes, and 3) catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2-oxoglutarate, propionate, 1 ,3- propanediol, succinate, ethanol, lactate, butyrate, 2,3-butanediol, acetone, butanol, formate, H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2- methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3- (1 H-indol-3-yl)propanoate, 5- aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7-oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0214] In some embodiments, the microbial consortium: 1) metabolizes one or more than one metabolite produced by the plurality of active microbes, wherein the one or more than one metabolite inhibits metabolism of the first metabolic substrate by one or more of the plurality of active microbes, 2) increases the flux of a precursor of the first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate, 3) enhances one or more than one characteristic of the plurality of active microbes when administered to an animal selected from the group consisting of: a) gastrointestinal engraftment, b) biomass, c) first metabolic substrate metabolism, and d) longitudinal stability as compared to administration of the plurality of active microbes in the absence of the supportive community of microbes, and 4) catalyzes one or more than one reaction selected from the group consisting of: fermentation of polysaccharides to one or more than one of the group consisting of acetate, acetoin, 2-oxoglutarate, propionate, 1 ,3- propanediol, succinate, ethanol, lactate, butyrate, 2,3-butanediol, acetone, butanol, formate,H2, and CO2, fermentation of amino acids to one or more than one of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2- methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloretate, 3- (1 H-indol-3-yl)propanoate, 5- aminopentanoate, H2, H2S, and CO2, synthesis of one or more than one of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2, and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; synthesis of succinate from formate and fumarate, and butyrate, acetate, H2, and CO2 from lactate, deconjugation of conjugated bile acids to produce primary bile acids, conversion of cholic acid (CA) to 7-oxocholic acid, conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and conversion of 7- oxochenodeoxycholic acid to ursodeoxycholic acid (LIDCA).

[0215] In some embodiments, at least one of the two following conditions is met: the first metabolic substrate metabolizing activity of at least one of the plurality of active microbes is significantly different when measured in a standardized substrate metabolization assay at two pH values within a range of 4 to 8, and wherein the difference between the two pH values is at least one pH unit, and the first metabolic substrate metabolizing activity of at least one of the plurality of active microbes is significantly different when measured in a standardized substrate metabolization assay at two first metabolic substrate concentrations within a 100 fold range, and wherein the difference between the two first metabolic substrate concentrations is at least 1.2-fold.

[0216] In some embodiments, the microbial consortium comprises a plurality of between 1 and 1000 defined microbial strains, wherein the defined gut microbial community is capable of: a. metabolizing at least 90% of enumerated substrates selected from the group consisting of: a-mannan (yeast), acetate, agarose, alanine, alginate, anthocyanin, arabinan, arabinogalactan, arabinoxylan, arginine, asparagine, Aspartate, b- glucans, butyrate, carrageenan, chitin, chlorogenic acids, chondroitin sulfate, cinnamic acid, Cysteine, dextran (40), Dihydrochalcones, Enterodiol, flavan-3- ols, flavanones, flavones, flavonols, folate, formate, galactomannan (carob), galacturonan (homo), galacturonate, glucomannan (konjac), glutamate, Glutamine, Glycine, Histidine, hyaluronan, hydrogen, hydroxycinnamic acids, hydroxyproline, inulin, isoflavones / isoflavanones, Isoleucine, lactate, laminarin, Leucine, levan, Lysine, Methionine, mucin O-linked glycans, Ornithine, Phenylalanine, porphyran, Proline, propionate, rhamnogalacturonan I, rhamnogalacturonan II, Secoisolariciresinol diglucoside, Serine, starch (potato), starch (structure 1), thiamine, Threonine, tryptophan, Tyrosine, Valine, xyloglucan, and xylooligosaccharides (XOS), and / or b. producing at least 90% of enumerated metabolites selected from the group consisting of: formate, acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, 2-methylbutyrate, caporate, isocaporate, 3-methylvaleric acid, L- phenylalanine, 3-phenylpropionic acid, phyenypyruvate,DL-3-phenyllactic acid, trans-cinnamic acid, phenyllactic acid, phenethylamine, L-tyrosine, 3- (4- hydroxyphenyl)propionic acid, 3-(4-hydroxyphenyl) pyruvic acid, DL-p- hydroxyphenyl lactic acid, p-coumaric acid, 4-hydroxyphenyl acetic acid, tyramine, phenol, p-cresol, 4- ethylphenol, 4-vinylphenol, 4-hydroxybenzoic acid, L-tryptophan, 3-indolepropionic acid, 3- indolepyruvic acid, DL-indole-3 -lactic acid, trans-3-indoleacrylic acid, 3-indoleacetic acid, tryptamine, indole, skatol, indole-3 -carboxylic acid, indole-3 -carboxyaldehyde, N-acetyl-L- phenylalanine, phenylpropionylglycine, 3-(3-hydroxyphenyl) propionic acid, cinnamoylglycine, phenylacetylglycine, phenylacetylglutamine, hippuric acid, 2-hydroxyhippuric acid, 3- hydroxyhippuric acid, 4-hydroxyhippuric acid, 4- hydroxyphenylacetylglycine, phenyl sulfate, phenyl glucuronide, p-cresol sulfate, p-cresol glucuronide, 4-ethylphenol sulfate, 4- ethylphenol glucuronide, N-acetyl- L-tryptophan, 5 -hydroxy -L-typtophan, N-acetyl serotonin, 3- indolepriopionylglycine, indolyl-3-acryloylglycine, indoxyl sulfate, indoxyl glucuronide, 5- hydroxyindole-3-acetic acid, indoleacetylglycine, lithocholic acid, murocholic acid, ursodeoxycholic acid, hyodeoxycholic acid, deoxycholic acid, 7-oxocholic acid, co-muricholic acid, a-muricholic acid, b-muricholic acid, g- muricholic acid, 7Pcholic acid, taurolithocholic acid, tauroursodeoxycholic acid, taurohyodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, tauro-P-muricholic acid, tauro- co-muricholic acid, and taurocholic acid, wherein the defined gut microbial community achieves substantial engraftment when administered to a gnotobiotic mouse; and wherein the engrafted defined gut microbial community is stable following a human fecal community microbial challenge.

[0217] In some embodiments, the metabolization of a substrate and / or production of a product can be determined by administering the defined gut microbial community to a gnotobiotic mouse and measuring whether the substrate is metabolized and / or the product is produced after a defined period of time by liquid chromatography-mass spectrometry analysis of a sample obtained from the mouse.

[0218] In some embodiments, the microbial consortium comprises microbes that comprises a gene that is responsible for a phenotype selected from the group consisting of: reducing endogenous sulfide levels in the colon of a patient in need thereof; sulfide consumption; reducing sulfide and nitric oxide load on epithelial cells which affects cell respiration leading to a metabolic lesion; reducing relative abundance and or metabolic activity of sulfidogenic microbiota; reducing sulfide levels in the colon directly through consumption / assimilation; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by metabolic substrate competition; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by diverting metabolic substrates away from the production of sulfide; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by consuming H2; reducing sulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota by reducing release of metabolizable sulfur substrates; reducingsulfide levels, relative abundance and or metabolic activity of sulfidogenic microbiota by reducing sulfur amino acid release (methionine, cysteine, homocysteine and / or taurine) into the colon; reducing colonic protein fermentation; reducing nitric oxide production in the colon; reducing nitric oxide levels in the colon; and inducing colonocyte apoptosis in lesions to break an induced stable inflammatory state. Accordingly, in an example, compositions and formulations of the disclosure may be characterized based on capacity to reduce sulfide production. Reduced sulfide production may be determined in vitro, using, for example, a suitable assay. Alternatively, reduced sulfide production may be determined based on assessment of a subject following administration of a composition or formulation disclosed herein.

[0219] In some embodiments, the microbial consortium comprises microbes that comprise a gene that is responsible for the phenotype of sulfide consumption.

[0220] In some embodiments, the sulfide is present in a form of sulfide selected from the group consisting of: a sulfide ion (S2-); a bisulfide ion (SH_), an organic compound containing the group R-SH (a thiol); and hydrogen sulfide (H2S).

[0221] In some embodiments, the microbial consortium comprises microbes that comprises a gene selected from the group consisting of: genes responsible for the use of sulfide in the biosynthesis of methionine and cysteine.

[0222] In some embodiments, the composition comprises a plurality of microbes.

[0223] In some embodiments, the composition is capable of: a. metabolizing at least 85%; 86%; 87%; 88%; 89%; 90%; 91%; 92%; 93%; 94%; 95%; 96%; 97%; 98%; 99%; or 100% of the substrates selected from the group consisting of: glucomannan (konjac); galacturonate; hydroxyproline; rhamnogalacturonan i; galacturonan (homo); aspartate; dextran (40); galactomannan (carob); phenylalanine; leucine; histidine; arabinogalactan; arabinan; chondroitin sulfate; dihydrochalcones; mucin o-linked glycans; alginate; glycine; glutamine; xyloglucan; laminarin; flavonols; proline; anthocyanin; glutamate; folate; asparagine; thiamine; isoflavones / isoflavanones; starch (structure 1); butyrate; cysteine; porphyran; starch (potato); acetate; inulin; enterodiol; xylooligosaccharides (xos); arabinoxylan; cinnamic acid; rhamnogalacturonan ii; flavones; hydroxycinnamic acids; flavanones; flavan-3-ols; arabinose; a-mannan (yeast); methionine; threonine; arginine; flavan-3-ols; tyrosine; propionate; serine; chitin; laminarin; valine; carrageenan; formate; ornithine; alanine; hydrogen; dihydrochalcones; lactate; flavan-3-ols; isoleucine; rhamnogalacturonan i; xylooligosaccharides (xos); enterodiol; secoisolariciresinol diglucoside; hydroxyproline; dextran (40); and levan; and b-glucans, and / or b. producing at least 85%; 86%; 87%; 88%; 89%; 90%; 91 %; 92%; 93%; 94%; 95%; 96%; 97%; 98%; 99%; or 100% of the metabolites selected from the group consisting of: 3-methylvaleric acid; phenylpropionylglycine; N-acetyl- L-phenylalanine; tauro- co-muricholic acid; N-acetyl serotonin; deoxycholic acid; tyramine; propionate; murocholic acid; phenethylamine; formate; isocaporate; 4-ethylphenolglucuronide; isovalerate; DL-3-phenyllactic acid; p-coumaric acid; 4-hydroxyhippuric acid; caporate; 4- hydroxyphenylacetylglycine; 2-hydroxyhippuric acid; phenylacetylglycine; trans- 3-indoleacrylic acid; 7Pcholic acid; indoleacetylglycine; DL-indole-3 -lactic acid; 3- indolepyruvic acid; lithocholic acid; 4-hydroxybenzoic acid; cinnamoylglycine; phenylacetylglutamine; N-acetyl- L-tryptophan; indoxyl glucuronide; phenol; taurohyodeoxycholic acid; DL-p- hydroxyphenyl lactic acid; 4-ethylphenol sulfate; p-cresol glucuronide; 3-(4-hydroxyphenyl) pyruvic acid; trans-cinnamic acid; 3-indoleacetic acid; taurochenodeoxycholic acid; L-tryptophan; 5-hydroxyindole-3-acetic acid; acetate; taurolithocholic acid; 5 -hydroxy -L-typtophan; phenyl sulfate; isobutyrate; phenyllactic acid; tauro-P-muricholic acid; ursodeoxycholic acid; indoxyl sulfate; L- phenylalanine; skatol; taurocholic acid; 4-vinylphenol; phyenypyruvate; valerate; phenyl glucuronide; 3- indolepropionic acid; taurodeoxycholic acid; 2-methylbutyrate; indole; 4-hydroxyphenyl acetic acid; 3-(3-hydroxyphenyl) propionic acid; phenylpropionylglycine; phenylacetylglycine; indolyl- 3-acryloylglycine; tryptamine; co-muricholic acid; b-muricholic acid; hyodeoxycholic acid; cinnamoylglycine; 3-indolepriopionylglycine; indole-3 -carboxyaldehyde; a-muricholic acid; indole-3 -carboxylic acid; phenylacetylglutamine; phenylacetylglycine; 4-ethylphenol; phenol; taurocholic acid; 3-(4- hydroxyphenyl)propionic acid; tauro- co-muricholic acid; 3- hydroxyhippuric acid; taurolithocholic acid; phenyl sulfate; 7-oxocholic acid; tauro-P-muricholic acid; propionate; indoleacetylglycine; phenyl glucuronide; indoleacetylglycine; 3-indolepyruvic acid; murocholic acid; tyramine; taurohyodeoxycholic acid; and isobutyrate.

[0224] In some embodiments, metabolization of a substrate is determined by culturing the community of microbes and measuring whether the substrate is metabolized and / or the metabolite is produced by liquid chromatography-mass spectrometry analysis.

[0225] In some embodiments, production of a metabolite is determined by culturing the community of microbes and measuring whether the substrate is metabolized and / or the metabolite is produced by liquid chromatography-mass spectrometry analysis.

[0226] In some embodiments, metabolization of a substrate can be determined by administering the community of microbes to a gnotobiotic mouse and measuring whether the substrate is metabolized and / or the product is produced after a defined period of time by liquid chromatography-mass spectrometry analysis.

[0227] In some embodiments, production of a product can be determined by administering the community of microbes to a gnotobiotic mouse and measuring whether the substrate is metabolized and / or the product is produced after a defined period of time by liquid chromatography-mass spectrometry analysis.

[0228] In some embodiments, the defined period of time is a time period selected from the group consisting of: 1 hour; 2 hours; 4 hours; 8 hours; 12 hours; 24 hours; 2 days; 7 days; 14 days; 1 month; and 2 months.

[0229] In some embodiments, the composition encodes enzymes catalyzing all reactions at least 85%; at least 86%; at least 87%; at least 88%; at least 89%; at least 90%; at least 91 %; at least 92%; at least 93%; at least 94%; at least 95%; at least 96%; at least 97%; at least 98%; at least 99%; or at least 100% of the MetaCyc metabolic pathways selected from the group consisting of: valine-syn-pwy; lysine-deg-1-pwy; pwy-622; trpiacat-pwy; citrulbio- pwy; alanine-syn2-pwy; pwy-7400; serdeg-pwy; pwy-7297; glusyn-iii-pwy; alanine-deg3-pwy; cysts-deg-pwy; beta-ala-degradation-i-pwy; hisdeg-pwy; pro-syn-pwy; arg-degrad-pwy; entbac-syn-pwy; tau-deg-pwy; pwy-7414; pwy-6936; glutde-g-i-pwy; gly-g-syn-ala-pwy; lysine-deg-ii-pwy; his-syn-pwy; pwy-609; pwy-320; ethyl-pwy; pwy-6533; aspasn-pwy; glusyn- pwy; pwy-7104; pwy-426; meth-anal-pwy; pwy-6790; phos-lip-syn-2-pwy; pwy-5739; pwy- 6486; pwy-5921 ; trna-charging-pwy; pwy-7030; pwy-2841 ; pwy-6045; pwy-748; pwy-5221 ; pwy-710; pwy-4107; pwy-6130; pwy-8403; arg-deg-v-pwy; pwy-6039; pwy-7147; pwy-7221 ; arg-glu-pwy; pwy-7101 ; pwy-6196; pwy-7432; ala-cat-2-pwy; arg-deg-iii-pwy; phenylalanine- deg-i-pwy; cys-syn-pwy; spingolipid-syn-pwy; pwy-5818; trypdeg-pwy; pwy-7000; pwy-5863; homocys-degr-pwy; pwy-6240; pwy-5958; pwy-8102; arg-deg-i-v-pwy; trpkyn-cat-pwy; gly-g- pwy; pwy-5978; pro-ut-pwy; pwy-610; pwy-6818; pwy-8032; glusyn-pwy; pyridnuc-sal-pwy; pwy-5297; homoser-met-syn-pwy; alanine-valine-syn-pwy; threonine-deg-2-pwy; pwy-761 ; pwy-5913; thr-dlct-cat-pwy; gln-syn-pwy; pwy-6030; pwy-7430; pwy-7304; trpsyn-pwy; meth- acetate-pwy; sam-pwy; pwy-5458; pwy-4031 ; pwy-1781 ; pwy-8013; pwy-7025; pwy-5936; arg-ase-deg-pwy; glugln-syn-pwy; glutamin-deg-pwy; pwy-8071 ; glutamin-fum-pwy; pwy- 1121 ; pwy-3338; pwy-5002; taurine-deg-pwy; hydroxyprodeg-pwy; pwy-840; pwy-7930; pwy- 7014; asp-syn-pwy; glusyn-ii-pwy; pwy-402; arg-pro-pwy; pwy-4020; asn-deg-1-pwy; glusyn- pwy; arg-syn-4-pwy; pwy-5188; pwy-5766; asp-syn-pwy; pwy-8045; ala-cat-2-pwy; pwy-3155; pyriod-xsyn-pwy; pwy-5394; arg-synb-sub-pwy; lysine-amino-ad-pwy; beta-ala-degradation-i- pwy; pwy-8007; pwy-7030; pwy-6717; pwy-6263; pwy-5936; glut-deg-pwy; pwy-4070; val-deg- pwy; citrulline-deg-pwy; asp-deg-1-pwy; asparaginesyn-pwy; glut-or-pwy; glusyn-pwy; pwy- 5710; pwy-861 ; pwy-7072; pwy-7986; trpsyn-pwy; pwy-8102; trna-charging-pwy; trpcat-pwy; trpkyn-cat-pwy; trpsyn-pwy; glnsyn-pwy; pwy-3341 ; pwy-7425; pwy-7432; pwy-7440; pwy- 6444; pwy-7688; pwy-6769; pwy-4020; pwy-3004; pwy-4984; pwy-6769; pwy-7160; pwy- 6196; pwy-6183; pwy-6181 ; asp-syn-pwy; pwy-8053; ala-cat-2-pwy; homocys-degr-pwy; pwy- 6364; pwy-700; pwy-6790; alanine-syn2-pwy; alanine-valine-syn-pwy; threonine-deg-2-pwy; pwy-761 ; pwy-5913; thr-dlct-cat-pwy; gln-syn-pwy; pwy-6030; pwy-7430; pwy-7304; trpsyn- pwy; meth- acetate- pwy; sam-pwy; pwy-5458; pwy-4031 ; pwy-1781 ; pwy-8013; pwy-7025; pwy-5936; arg-ase-deg-pwy; glugln-syn-pwy; glutamin-deg-pwy; pwy-8071 ; glutamin-fum- pwy; pwy-1121 ; pwy-3338; pwy-5002; taurine-deg-pwy; hydroxyprodeg-pwy; pwy-840; pwy- 7930; pwy-7014; asp-syn-pwy; glusyn-ii-pwy; pwy-402; arg-pro-pwy; pwy-4020; asn-deg-1- pwy; glusyn-pwy; arg-syn-4-pwy; pwy-5188; pwy-5766; asp-syn-pwy; pwy-8045; ala-cat-2- pwy; pwy-3155; pyriod-xsyn-pwy; pwy-5394; arg-synb-sub-pwy; lysine-amino-ad-pwy; beta-ala-degradation-i-pwy; pwy-8007; pwy-7030; pwy-6717; pwy-6263; pwy-5936; glut-deg-pwy; pwy-4070; val-deg-pwy; citrulline-deg-pwy; asp-deg-1-pwy; asparaginesyn-pwy; glut-or-pwy; glusyn-pwy; pwy-5710; pwy-861 ; pwy-7072; pwy-7986; trpsyn-pwy; pwy-8102; trna-charging- pwy; trpcat-pwy; trpkyn-cat-pwy; trpsyn-pwy; glnsyn-pwy; pwy-3341 ; pwy-7425; pwy-7432; pwy-7440; pwy-6444; pwy-7688; pwy-6769; pwy-4020; pwy-3004; pwy-4984; pwy-6769; pwy- 7160; pwy-6196; pwy-6183; pwy-6181 ; asp-syn-pwy; pwy-8053; ala-cat-2-pwy; homocys- degr-pwy; pwy-6364; pwy-700; pwy-6790; alanine-syn2-pwy; alanine-valine-syn-pwy; threonine-deg-2-pwy; pwy-761 ; pwy-5913; thr-dlct-cat-pwy; gln-syn-pwy; pwy-6030; pwy- 7430; pwy-7304; trpsyn-pwy; meth- acetate- pwy; sam-pwy; pwy-5458; pwy-4031 ; pwy-1781 ; pwy-8013; pwy-7025; pwy-5936; arg-ase-deg-pwy; glugln-syn-pwy; glutamin-deg-pwy; pwy- 8071 ; glutamin-fum-pwy; pwy-1121 ; pwy-3338; pwy-5002; taurine-deg-pwy; hydroxyprodeg- pwy; pwy-840; pwy-7930; pwy-7014; asp-syn-pwy; glusyn-ii-pwy; pwy-402; arg-pro-pwy; pwy- 4020; asn-deg-1-pwy; glusyn-pwy; arg-syn-4-pwy; pwy-5188; pwy-5766; and asp-syn (as defined in WO2021 / 237162).

[0230] In some embodiments, encoding the enzymes catalyzing all reactions of a MetaCyc metabolic pathway can be determined by culturing the community of microbes and measuring whether a substrate in the pathway is metabolized, a metabolite in the pathway is produced, and / or a reaction intermediate in the pathway is produced by liquid chromatography-mass spectrometry analysis.

[0231] In some embodiments, encoding the enzymes catalyzing all reactions of a MetaCyc metabolic pathway can be determined by administering the community of microbes to a gnotobiotic mouse and measuring whether a substrate in the pathway is metabolized, a metabolite in the pathway is produced, and / or a reaction intermediate in the pathway is produced after a defined period of time by liquid chromatography-mass spectrometry analysis of a sample obtained from the mouse.

[0232] In some embodiments, the substrates or nutrients metabolized by a metabolic pathway are selected from the group consisting of: leucine; arabinan; acetate; chondroitin sulfate; dihydrochalcones; folate; laminarin; cinnamic acid; thiamine; isoflavones / isoflavanones; anthocyanin; arabinoxylan; starch (structure 1); isoleucine; butyrate; starch (potato); hydroxyproline; rhamnogalacturonan I; proline; galacturonate; galactomannan (carob); flavonols; glucose; arabinogalactan; valine; hydrogen; mucin O-linked glycans; xyloglucan; formate; flavan-3-ols; tyrosine; threonine; glyc; rhamnogalacturonan II; phenylalanine; xanthan gum; chitin; b-glucans; flavanones; propionate; hydroxycinnamic acids; hyaluronan; asparagine; glutamine; alanine; glutamate; alginate; enterodiol; arabinogalactan; xylooligosaccharides (XOS); seciosolariciresinol diglucoside; histidine; arabinoxylan; mucin O-linked glycans; dextran (40); glucomannan (konjac); and alginate.

[0233] In some embodiments, the substrates or nutrients metabolized by a metabolic pathway comprises at least 85%; at least 86%; at least 87%; at least 88%; at least 89%; atleast 90%; at least 91%; at least 92%; at least 93%; at least 94%; at least 95%; at least 96%; at least 97%; at least 98%; at least 99%; or at least 100%; of the substrates described herein.

[0234] In some embodiments, the metabolites synthesized or produced by a metabolic pathway are selected from the group consisting of: acetate; 2-hydroxyhippuric acid; 3-(3- hydroxyphenyl)propionic acid; 3-(4-hydroxyphenyl)propionic acid; 3-(4-hydroxyphenyl)pyruvic acid; 3-indoleacetic acid; 3-indolepropionic acid; 3-indolepropionylglycine; 3-indolepyruvic acid; 3-methyl valeric acid; 4-ethylphenol; 4-ethylphenol glucuronide; 4-ethylphenol sulfate; 4- hydroxybenzoic acid; 4-hydroxyphenyl acetic acid; 4-hydroxyphenylacetylglycine; 4- hydroxyhippuric acid; 4-vinylphenol; 5-hydroxy-L-tryptophan; p-muricholic acid; a-muricholic acid; y-muricholic acid; co-muricholic acid; caproate; cinnamoylglycine; DL-3-phenyllactic acid; DL-indole-3-lactic acid; DL-p-hydroxyphenyl lactic acid; deoxycholic acid; formate; hyodeoxycholic acid; indole; indole-3-carboxy aldehyde; indole-3-carboxylic acid; indoleacetylglycine; indolyl-3-acryloylglycine; indoxyl glucuronide; indoxyl sulfate; isobutyrate; isocaproate; isovalerate; L-phenylalanine; L-tryptophan; lithocholic acid; murocholic acid; N- acetyl-L-phenylalanine; N-acety I- L-tryptophan; N-acetyl serotonin; phenethylamine; phenol; phenylacetylglycine; phenylacetylglutamine; phenylpropionylglycine; phenylpyruvate; phenyl sulfate; phenyl glucuronide; propionate; p-coumaric acid; p-cresol; p-cresol sulfate; p-cresol glucuronide; skatol; taurocholic acid; taurodeoxycholic acid; tauro-p-muricholic acid; tauro-co- muricholic acid; taurochenodeoxycholic acid; tauroursodeoxycholic acid; tauroursodeoxycholic acid; taurohyodeoxycholic acid; trans-3-indoleacrylic acid; transcinnamic acid; tryptamine; valerate; ursodeoxycholic acid; 7-oxocholic acid; and 7a-cholic acid.

[0235] In some embodiments, the metabolites synthesized or produced by a metabolic pathway comprise at least 85%; at least 86%; at least 87%; at least 88%; at least 89%; at least 90%; at least 91%; at least 92%; at least 93%; at least 94%; at least 95%; at least 96%; at least 97%; at least 98%; at least 99%; or at least 100%; of the substrates described herein.

[0236] In some embodiments, the microbial communities metabolize at least 85% (e.g. ., at least 85%; 86%; 87%; 88%; 89%; 90%; 91 %; 92%; 93%; 94%; 95%; 96%; 97%; 98%; 99%; or 100%) of the substrates described above and produce at least 85% (e.g., at least 85%; 86%; 87%; 88%; 89%; 90%; 91%; 92%; 93%; 94%; 95%; 96%; 97%; 98%; 99%; or 100%) of the metabolites described herein.

[0237] In some embodiments, the microbial communities metabolize at least 85% (e.g., at least 85%; 86%; 87%; 88%; 89%; 90%; 91 %; 92%; 93%; 94%; 95%; 96%; 97%; 98%; 99%; or 100%l) of the substrates described above and utilize at least 85% (e.g., at least 85%; 86%; 87%; 88%; 89%; 90%; 91%; 92%; 93%; 94%; 95%; 96%; 97%; 98%; 99%; or 100%) of the MetaCyc metabolic pathways described herein.

[0238] In some embodiments, the composition is assembled to produce at least 85% (e.g., at least 85%; 86%; 87%; 88%; 89%; 90%; 91 %; 92%; 93%; 94%; 95%; 96%; 97%; 98%;99%; or 100%) of the metabolites described above and utilize at least 85% (e.g., at least 85%; 86%; 87%; 88%; 89%; 90%; 91%; 92%; 93%; 94%; 95%; 96%; 97%; 98%; 99%; or 100%l) of the MetaCyc metabolic pathways described herein.

[0239] In some embodiments, the composition achieves substantial engraftment when administered to a gnotobiotic mouse.

[0240] In some embodiments, the community of microbes is stable following a human fecal community microbial challenge.

[0241] In some embodiments, the composition comprises two or more microbial consortiums.

[0242] In some embodiments, the composition is supplemented with a biological active ingredient or agent.

[0243] In some embodiments, biotherapeutic composition comprising the composition of an embodiment of the disclosure, together with an acceptable diluent or carrier.

[0244] In some embodiments, a pharmaceutical composition comprising the composition of an embodiment of the disclosure, together with a pharmaceutically acceptable diluent or carrier.

[0245] In some embodiments, a dosage form comprising the composition according to an embodiment of the disclosure.

[0246] In some embodiments, the dosage form is a unity dosage form.

[0247] In some embodiments, an isolated non-inflammatory strain of bacteria comprising a 16S ribosomal RNA (rRNA) gene having a nucleotide sequence selected from the group consisting of: SEQ ID NOs: 1 to 286.

[0248] In some embodiments, at least one strain of bacteria comprises a 16S ribosomal RNA (rRNA) gene have a sequence identity to one or more SEQ ID NOs: 1 to 286, wherein the sequence identity is selected from the group consisting of: at least 99.9%; at least 99%; at least 98%; at least 97%; at least 96%; at least 95%; at least 94%; at least 93%; at least 92%; at least 91 %; and at least 90%.

[0249] In some embodiments, a novel species or strain of microbe, wherein the microbe is selected from the group consisting of: any one of the species selected from a table selected from: Table 9; Table 10; Table 11 ; Table 12; Table 13; Table 14; Table 15; Table 16.

[0250] In some embodiments, the microbe has a less than 97% sequence identity (16S) to the NCBI 16S refSEQ database.

[0251] Some embodiments provided herein relate to a formulation comprising: the composition of an embodiment of the disclosure, wherein the formulation is formulated as a capsule, tablet, or powder.

[0252] In some embodiments, a formulation comprising: a plurality of core community microbial species, wherein said core community microbial species comprise members of at least the following genera: Dysosmobacter, Enterocloster, Ruthenibacterium, Vescimonas,Phocaeicola, Pusillimonas, Solibaculum, and Christensenella, a plurality of keystone microbial species, wherein said keystone microbial species comprise members of at least the genus Phocaeicola, and a non-naturally occurring pharmaceutically acceptable excipient, wherein the formulation is formulated as a capsule, tablet, or powder.

[0253] In some embodiments, the plurality of core community microbial species comprises at least the following species: Dysosmobacter welbionis, Enterocloster bolteae, Ruthenibacterium lactatiformans, Vescimonas coprocola, Phocaeicola salanitronis, Pusillimonas faecalis, Solibaculum mannosilyticum, Chrstensenella minuta, Alistipes magaguti, Parabacteroides goldsteinii, Alistipes communis, Ruminococcus bicirculans, Bacteroides caecimuris, Alistipes dispar, and Bacteroides salversiae', and wherein the plurality of keystone microbial species comprises at least the following species: Phocaeicola coprocola, Bifidobacterium bifidum, and Coprococcus catus.

[0254] In some embodiments, the plurality of core community microbial species comprises at least the following species: Alistipes dispar, Bacteroides salyersiae, Bifidobacterium bifidum, Christensenella minuta, Coprococcus catus, Coprococcus spOO0154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis, Parabacteroides goldsteinii, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, and Vescimonas coprocola.

[0255] In some embodiments, a formulation comprising: a plurality of core community microbial species, wherein said core community microbial species comprise members of at least one of the following genera: Dysosmobacter, Enterocloster, Ruthenibacterium, Vescimonas, Phocaeicola, Pusillimonas, Solibaculum, and Christensenella, a plurality of keystone microbial species, wherein said keystone microbial species comprise members of at least the genus Phocaeicola, and a non-naturally occurring pharmaceutically acceptable excipient, wherein the formulation is formulated as a capsule, tablet, or powder.

[0256] In some embodiments, the plurality of core community microbial species comprises at least one of the following species: Dysosmobacter welbionis, Enterocloster bolteae, Ruthenibacterium lactatiformans, Vescimonas coprocola, Phocaeicola salanitronis, Pusillimonas faecalis, Solibaculum mannosilyticum, Chrstensenella minuta, Alistipes magaguti, Parabacteroides goldsteinii, Alistipes communis, Ruminococcus bicirculans, Bacteroides caecimuris, Alistipes dispar, and Bacteroides salversiae’, and wherein the plurality of keystone microbial species comprises at least one of the following species: Phocaeicola coprocola, Bifidobacterium bifidum, and Coprococcus catus.

[0257] In some embodiments, the plurality of core community microbial species comprises at least one of the following species: Alistipes dispar, Bacteroides salyersiae, Bifidobacterium bifidum, Christensenella minuta, Coprococcus catus, Coprococcus spOO0154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis,Parabacteroides goldsteinii, Ruminococcus bicirculans, Rutheni bacterium lactatiformans, Solibaculum mannosilyticum, and Vescimonas coprocola.

[0258] In some embodiments, the formulation is generated by co-culturing the core community microbial species and the keystone microbial species in a single bioreactor.

[0259] In some embodiments, the formulation is configured to metabolize hydrogen sulfide in the gastrointestinal tract of a subject post administration of the formulation.

[0260] In some embodiments, the formulation is formulated for oral delivery.

[0261] In some embodiments, the formulation is lyophilized.

[0262] In some embodiments, the pharmaceutically acceptable excipient comprises maltodextrin.

[0263] In some embodiments, the formulation further comprises a prebiotic.

[0264] In some embodiments, the formulation is encapsulated within an enteric coating.

[0265] In some embodiments, the plurality of core community microbial species comprises all of the minimum core species in Table 14. In some embodiments, the plurality of core community microbial species comprises all of the minimum core species in any one of T able 33, T able 34, T able 35 or T able 36.

[0266] In some embodiments, the plurality of keystone microbial species comprises all of the keystone species in Table 13.

[0267] In some embodiments, a formulation comprising a plurality of microbial species comprising all of the species of Tables 13 and 14.

[0268] While compositions of the disclosure can comprise large numbers of microbes, in an example, the minimum number of microbes selected from an above referenced Table is between 10 to 50. In another example, the minimum number of microbes selected from an above referenced Table is between 15 to 25. In another example, the minimum number of microbes selected from an above referenced Table is between 10 to 25. In another example, the minimum number of microbes selected from an above referenced Table is between 5 to 25. In another example, the minimum number of microbes selected from an above referenced Table is between 5 to 20. In another example, the minimum number of microbes selected from an above referenced Table is between 10 to 20. In another example, the minimum number of microbes selected from an above referenced Table is between 15 to 20. In another example, the minimum number of microbes selected from an above referenced Table is between 5 to 15.

[0269] The use of the formulation of an embodiment of the disclosure for the treatment of dysbiosis.

[0270] The use of the formulation of an embodiment of the disclosure for the treatment of ulcerative colitis.

[0271] The use of the formulation of an embodiment of the disclosure for the treatment of Crohn’s Disease.

[0272] The use of the formulation of an embodiment of the disclosure for the treatment of one or more diseases or disorders selected from the group consisting of: inflammatory bowel disease, checkpoint inhibitor colitis, primary sclerosing cholangitis, non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, alcoholic hepatitis, hepatic encephalopathy, obesity, insulin resistance, type 2 diabetes, melanoma, renal cell carcinoma, bowel cancer and precancerous polyps, lymphoma, leukemia, myeloma, pancreatic cancer, breast cancer, lung cancer, testicular cancer, sarcoma, dyslipidaemia, atherosclerotic heart disease, hypertension, type 1 diabetes, rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematous, Sjogren’s disease, food allergy, anaphylaxis, atopic dermatitis, atopic rhinitis or sinusitis, clostridioides difficile infection, multidrug resistant infection or colonisation, renal tract or urinary tract infections, blood stream infections, respiratory infections, sepsis, autism, multiple sclerosis, Parkinson’s disease, depression, anxiety, bipolar disorder, and schizophrenia.

[0273] In some embodiments, in combination with a therapy specific to the one or more diseases or disorders.

[0274] In some embodiments, the formulation comprises a ratio of core community microbial strains to keystone microbial strains of 10:1. 9:1 , 8:1 , 7:1 , 6:1 , 5:1 , 4:1 , 3:1 , 2:1 , or 1 :1 with respect to number of bacteria.

[0275] In some embodiments, the formulation comprises from 50% to 80% core community microbial strains and from 20% to 50% keystone microbial strains as a percentage of total microorganisms in the formulation.

[0276] In some embodiments, the plurality of core community microbial species comprise minimum core species selected from the strains identified in Table 14. In some embodiments, the plurality of core community microbial species comprise minimum core species selected from the strains identified in Table 34, Table 35 or Table 36.

[0277] In some embodiments, the plurality of keystone microbial species comprise keystone species selected from the strains identified in Table 13.

[0278] In some embodiments, a formulation for oral administration comprises: a plurality of core community microbial species; and a plurality of keystone microbial species, wherein the plurality of core community microbial species are species of at least the following genera: Akkermansia, Alistipes, Bacteroides, Bifidobacterium, Butyricimonas, Christensenella, Clostridium, Collinsella, Coprococcus, Dysosmobacter, Enterocl oster, Faecalibacterium, Para bacteroides, Phocaeicola, Pusillimonas, Ruminococcus, Ruthenibacterium, Solibaculum, and Vescimonas; and wherein the plurality of keystone microbial species are species of at least the following genera: Alistipes, Bacteroides, Bifidobacterium, Coprococcus, Faecalibacterium, Methanobrevibacter, Parabacteroides, Phocaeicola, Roseburia, Ruminococcus, and Subdoligranulum.

[0279] In some embodiments, a formulation comprises: a plurality of core community microbial species, wherein said core community microbial species comprise members of at least the following genera: Dysosmobacter, Enterocloster, Ruthenibacterium, Vescimonas, Phocaeicola, Pusillimonas, Solibaculum, and Christensenella, a plurality of keystone microbial species, wherein said keystone microbial species comprise members of at least the genus Phocaeicola, and a non-naturally occurring pharmaceutically acceptable excipient, wherein the formulation is formulated as a capsule, tablet, or powder.

[0280] In some embodiments, a formulation comprises: plurality of core community microbial species comprises at least one of the following species: Dysosmobacter welbionis, Enterocloster bolteae, Ruthenibacterium lactatiformans, Vescimonas coprocola, Phocaeicola salanitronis, Pusillimonas faecalis, Solibaculum mannosilyticum, Chrstensenella minuta, Alistipes magaguti, Parabacteroides goldsteinii, Alistipes communis, Ruminococcus bicirculans, Bacteroides caecimuris, Alistipes dispar, and Bacteroides salversiae', and wherein the plurality of keystone microbial species comprises at least one of the following species: Phocaeicola coprocola, Bifidobacterium bifidum, and Coprococcus catus.

[0281] In some embodiments, a formulation comprises: a plurality of core community microbial species, wherein said core community microbial species comprise members of at least the following species: Alistipes dispar, Bacteroides salyersiae, Bifidobacterium bifidum, Christensenella minuta, Coprococcus catus, Coprococcus spOO0154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis, Parabacteroides goldsteinii, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, Vescimonas coprocola.

[0282] In some embodiments, a formulation comprises a plurality of core community microbial species and a plurality of keystone microbial species comprising 80-100% of the species identified on T ables 9; Table 10 or T able 11.

[0283] In some embodiments, a formulation comprises: a plurality of core community microbial strains in lyophilized form; a plurality keystone microbial strains in lyophilized form; at least one of a prebiotic, surfactant, a polyester, or a polyvinyl alcohol; and where the formulation is produced by co-culturing the plurality of core community microbial strains with the plurality keystone microbial strains in a single vessel.

[0284] In some embodiments, the formulation does not comprise any bacteria from the phylum Pseudomonadota or Campylobacterota.Methods of Co-culturing

[0285] Some embodiments provided herein relate to methods of co-culturing one or more core community microbial strains with one or more keystone microbial strains, comprising selecting one or more core community microbial strains selected from Table 14 and one ormore keystone microbial strains selected from Table 13, and co-culturing the strains under suitable culture conditions.

[0286] In some embodiments, the co-culture comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from Table 14 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 13.

[0287] In some embodiments, the co-culture comprises 20 or more core community microbial strains selected from Table 14 and 10 or more keystone microbial strains selected from Table 13.

[0288] In some embodiments, the microbial strains include microbial isolates selected from the group consisting of: organisms from Firmicutes (Bacillota); Bacteroidetes (Bacteroidota); Actinobacteria (Actinomycetota); Verrucomicrobiota; and Pseudomonadota.

[0289] In some embodiments, the microbial strains exclude species from Pseudomonadota, Campylobacterota, and Fusobacteria, or any combination thereof.

[0290] In some embodiments, the microbial strains exclude species selected from the group consisting of: Clostridium perfringens; Klebsiella pneumonia; Escherichia coli, Campylobacter jejuni; and Staphylococcus aureus.

[0291] In some embodiments, the culture produces a culture which can further include co-cultured isolates, individual strains, or combinations thereof mixed post-culture.

[0292] In some embodiments, the co-culture utilises a fed batch strategy.

[0293] In some embodiments, the co-culture is cultured under anaerobic conditions

[0294] In some embodiments, the co-culture is cultured in a single bioreactor or in a plurality of bioreactors.

[0295] In some embodiments, the co-culture medium comprises agents selected from the group consisting of: carbohydrates; amino acids; vitamins; organic acids, salts and minerals; redox indicators; or combinations thereof.

[0296] In some embodiments, the pH of the culture is is controlled within a range of 5-9 or 6.5-7.5.

[0297] In some embodiments, the culture comprises the steps of: CFU determination; inoculum preparation; bioreactor culturing; harvesting and formulation; and / or scaling up.Methods of application

[0298] Some embodiments provided herein relate to methods of administering the compositions provided herein to subject in need. In some embodiments, the methods include decreasing inflammation in a subject in need thereof, said method comprising administering to the subject an effective amount of the composition of an embodiment of the disclosure.

[0299] In some embodiments, the methods include decreasing dysbiosis in a subject in need thereof, said method comprising administering to the subject an effective amount of the composition of an embodiment of the disclosure.

[0300] In some embodiments, the dysbiosis and / or inflammation is associated with one or more of inflammatory bowel disease (IBD), pouchitis, irritable bowel syndrome (IBS), an enteric bacterial infection, a metabolic disease, a neuropsychiatric disorder, an autoimmune disease, an allergic disorder, hepatic encephalopathy, or a cancer.

[0301] In some embodiments, the methods include preventing or treating a medical disorder or disease associated with dysbiosis in a subject in need thereof, said method comprising administering to the subject an effective amount of the composition of an embodiment of the disclosure.

[0302] In some embodiments, the composition is produced from culturing the consortium in a bioreactor.

[0303] In some embodiments, the composition is healthy donor derived.

[0304] In some embodiments, the dysbiosis is an imbalance or perturbation of the microbiota.

[0305] In some embodiments, the dysbiosis is a disruption in the normal balance of microbial communities in the body, particularly the gut.

[0306] In some embodiments, the dysbiosis is an imbalance caused by a variety of reasons, such as antibiotics, certain diets, stress, or diseases.

[0307] In some embodiments, the dysbiosis leads to a number of health issues including inflammatory bowel diseases, allergy, irritable bowel syndrome, obesity, mental health and can affect the efficacy of cancer therapies.

[0308] In some embodiments, the dysbiosis is associated with an enteric bacterial infection or dominant strain, such as an infection or proliferation within the gastrointestinal tract of a pathogenic bacterium.

[0309] In some embodiments, said method demonstrates a property selected from the group consisting of:

[0310] In some embodiments, certain strains in the co-culture and / or formulation for administration to a subject are selected based on these phenotypes: a. emergent metabolic functions; b. emergent metabolic functions relating to: short-chain fatty acids (SCFAs); sulfide homeostasis; energy harvest; tryptophan metabolism; bile acid metabolism; vitamin production; and / or drug metabolism; c. synergistic metabolic functions and wherein the metabolic function of the consortium as a whole is greater than metabolic function of any of the individual isolates; d. synergistic metabolic functions and wherein the sulfide reduction metabolic function of the consortium as a whole is greater than sulfide reduction metabolic function of each of the individual isolates; e. synergistic metabolic functions and wherein the sulfide reduction metabolic function of the consortium as a whole is greater than the sulfide reduction metabolic functionof each of the individual isolates (and wherein the sulfide reduction metabolic function is selected from the group consisting of: microbial competition for metabolic substrates (such as volatile fatty acids (acetate, propionate, butyrate), organic acids (lactate, valerate, succinate, pyruvate), amino acids (alanine, glutamate, serine) and ethanol as electron donors in cellular respiration); reduced sulfur substrate release in the colon; removing sulfide from the colon (such as assimilation of sulfide to cysteine)); f. synergistic metabolic functions relating to: short-chain fatty acids (SCFAs); sulfide homeostasis; energy harvest; tryptophan metabolism; bile acid metabolism; vitamin production; drug metabolism; g. reduces sulfide and nitric oxide load on epithelial cells which leads to a metabolic lesion via inhibition of cellular respiration; h. reduces relative abundance and or metabolic activity of sulfidogenic microbiota in vitro; i. reduces sulfide levels in vitro either directly or indirectly through consumption / assimilation of sulfide or metabolic substrates and / or a reduction in the production of sulfide; j. reduces sulfide levels in vitro via metabolic substrate competition; k. reduces sulfide levels in vitro by consuming hydrogen; l. reduces relative abundance and or metabolic activity of sulfidogenic microbiota; m. reduces sulfide levels in the colon either directly or indirectly through consumption / assimilation of sulfide or metabolic substrates and / or a reduction in the production of sulfide; reduce sulfide levels in the colon via metabolic substrate competition; and or reduce sulfide levels in the colon by consuming hydrogen; n. reduces the relative abundance and or metabolic activity of sulfidogenic microbiota by reducing metabolizable sulfur substrates; reduce sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing protein fermentation; o. induces colonocyte apoptosis in lesions to break an induced stable inflammatory state driven; p. drives down undesired inflammation; q. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host protease activity; r. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host protease activity; s. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial protease activity; t. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing microbial protease activity; u. reduces sulfide (production in the colon by modulating host protease activity;v. reduces sulfide production in the colon by reducing host protease activity; w. reduces sulfide production in the colon by modulating microbial protease activity; x. reduces sulfide production in the colon by reducing microbial protease activity; y. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host antiprotease (protease inhibitor) activity; z. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host antiprotease (protease inhibitor) activity; aa. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial antiprotease (protease inhibitor) activity; ab. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) ac. reducing microbial antiprotease (protease inhibitor) activity; ad. reduces sulfide production in the colon by modulating host antiprotease (protease inhibitor) activity; ae. reduces sulfide production in the colon by reducing host antiprotease (protease inhibitor) activity; af. reduces sulfide production in the colon by modulating microbial antiprotease (protease inhibitor) activity; ag. reduces sulfide production in the colon by reducing microbial antiprotease (protease inhibitor) activity; ah. prevents or reduces activation of the mucosa immune system in a natural killer T-cell driven IL-13 and IL-5 dependent, TH2 mediated, immune response; ai. decreases inflammation in the subject; aj. decreases inflammation in the subject when measured by a parameter selected from the group consisting of: TNFo signaling via NF-KB; I FNO signaling; IFNy signaling; IL6 JAK STAT3 signaling; activation of pro-apoptotic pathways; initiation of unfolded protein response; ak. down regulates genes associated with pro-apoptotic pathways and the unfolded protein response, including genes selected from the group consisting of: CHAC1 , CEBPB, TRIB3, PPP1 R15A, DDIT3, ATF4 and XBP1 ; al. treats and / or prevents dysbiosis; am. treats or prevents a medical disorder or disease associated with dysbiosis; an. treats or prevents a medical disorder or disease associated with mycobiome dysbiosis; ao. treats and / or prevents a gastrointestinal disorder;ap. treats and / or prevents a gastrointestinal disorder; wherein the gastrointestinal disorder is selected from the group consisting of: irritable bowel syndrome; an ulcer of the gastrointestinal tract; a cancer of the gastrointestinal tract; aq. treats and / or prevents gastrointestinal tract mucosal inflammation; ar. treats and / or prevents gastrointestinal tract mucosal inflammation, wherein the inflammation is associated with one or more of disorders selected from the group consisting of: inflammatory bowel disease (IBD), pouchitis, irritable bowel syndrome (IBS), an enteric bacterial infection, a metabolic disease, a neuropsychiatric disorder, an autoimmune disease, an allergic disorder, hepatic encephalopathy, or a cancer; as. treats and / or prevents inflammatory bowel disease; at. treats and / or prevents ulcerative colitis; Crohn's disease; gastroenteritis; colitis; checkpoint inhibitor colitis; and pouchitis; au. treats and / or prevents one or more of diseases or disorders selected from the group consisting of: liver disorders; metabolic disorders; neurological disorders; oncology disorders; cardiovascular disorders; immunological disorders; allergy; allergic and atopic disorders; infectious disease; and can affect the efficacy of cancer therapies. In some embodiments, the liver disorder is selected from the group consisting of: Primary sclerosing cholangitis; Non-alcoholic steatohepatitis; Non-alcoholic fatty liver disease; Alcoholic hepatitis; and Hepatic encephalopathy. In some embodiments, the metabolic disorder is selected from the group consisting of: Obesity; Insulin resistance; and Type 2 diabetes. In some embodiments, the neurological disorder is selected from the group consisting of: Autism; Multiple sclerosis; Parkinson’s disease; Depression; Anxiety; Bipolar disorder; Schizophrenia; and Mental health. In some embodiments, the oncology disorder is selected from the group consisting of: Melanoma; Renal cell carcinoma; Bowel cancer and precancerous polyps; Lymphoma; Leukaemia; Myeloma; Pancreatic cancer; Breast cancer; Lung cancer; Testicular cancer; and Sarcoma. In some embodiments, the cardiovascular disorder is selected from the group consisting of: Dyslipidaemia; Atherosclerotic heart disease; and Hypertension. In some embodiments, the immunological disorder is selected from the group consisting of: Type 1 diabetes; Rheumatoid arthritis; Psoriatic arthritis; Psoriasis; Systemic Lupus Erythematous; and Sjogren’s disease. In some embodiments, the allergic or atopic disorder is selected from the group consisting of: Food allergy; Anaphylaxis; Atopic dermatitis; and Atopic rhinitis or sinusitis. In some embodiments, the infectious disease is selected from the group consisting of: Clostridioides difficile infection; Multidrug resistant infection or colonisation; Renal tract or urinary tract infections; Blood stream infections; Respiratory infections; and Sepsis. In some embodiments, the disease or disorder is associated with mycobiome dysbiosis; and In some embodiments, the disease or disorder is associated with dysbiosis; av. increases the relative abundance of a member of the bacteria genus or colonizes a member of the bacteria genus selected from the group consisting of:Acidaminococcaceae (family), Acidaminococcus, Adlercreutzia, Agathobaculum, Akkermansia, Alistipes, Alterilei bacterium, Amedibacillus, Amedibacterium, Aminipila, Anaerobutyricum, Anaerococcus, Anaerocolumna, Anaerofustis, Anaerostipes, Anaerotignum, Anaerotruncus, Bacillus, Bacteroides, Barnesiella, Bifidobacterium, Bilophila, Blautia, Butyricimonas, Butyrivibrio, Campylobacter, Caproicibacter, Caproicibacterium, Caproiciproducens, Casaltella, Catenibacterium, Christensenella, Clostridium, Collinsella, Coprobacillus, Coprobacter, Coprococcus, Desulfovibrio, Dorea, Duodenibacillus, Dysosmobacter, Eggerthella, Enorma, Enterocl oster, Enterococcus, Escherichia, Ethanoligenens, Eubacterium, Faecalibacillus, Faecalibacterium, Faecalibaculum, Finegoldia, Flavonifractor, Flintibacter, Fusicatenibacter, Gemmiger, Gordonibacter, Granulicatella, Herbinix, Holdemanella, Holdemania, Hoylesella, Hungatella, Intestinibacter, Intestinibaculum, Intestinimonas, Lachnoanaerobaculum, Lachnoclostridium, Lachnospira, Lachnospiraceae incertae sedis (unclassified rank, Lachnospiraceae family), Lacrimispora, Lactococcus, Ligilactobacillus, Longibaculum, Longicatena, Mageeibacillus, Maliibacterium, Marvinbryantia, Massilimicrobiota, Massiliprevotella, Massilistercora, Mediterraneibacter, Megamonas, Megasphaera, Merdibacter, Mesosutterella, Mitsuokella, Mogi bacterium, Muribaculum, Negativibacillus, Novisyntrophococcus, Odoribacter, Olsenella, Oscillibacter, Oscillospiraceae (family), Oscillospiraceae incertae sedis (unclassified rank, Oscillospiraceae family), Parabacteroides, Paraclostridium, Paraprevotella, Parolsenella, Peptacetobacter, Peptoniphilus, Peptostreptococcus, Phascolarctobacterium, Phocaeicola, Porphyromonas, Prevotella, Pseudobutyrivibrio, Pusillibacter, Romboutsia, Roseburia, Ruminiclostridium, Ruminococcus, Ruthenibacterium, Schaalia, Segatella, Selenomonas, Sellimonas, Senegalimassilia, Slackia, Sodaliphilus, Solibaculum, Streptococcus, Subdoligranulum, Thomasclavelia, Tyzzerella, Veillonella and Vescimonas or any combination, subgroup or multitude thereof; aw. reduces the relative abundance of a member of the bacteria genus or decolonises a member of the bacteria genus selected from the group consisting of: Achromobacter, Acidaminococcus, Aeromonas, Alicyclobacillus, Bacteroides, Bifidobacterium, Blautia, Bosea, Burkholderiales, Clostridium, Cutibacterium, Desulfovibrio, Eggerthella, Enterobacter, Enterococcus, Escherichia, Eubacterium, Flavonifractor, Granulicatella, Hungatella, Klebsiella, Ligilactobacillus, Mediterraneibacter, Minicystis, Oscillibacter, Parabacteroides, Pluralibacter, Prevotella, Prosthecochloris, Pseudomonas, Rhodococcus, Salmonella, Schaalia, Serratia, Shewanella, Staphylococcus, Streptomyces, Sutterella, Veillonella, or any combination, subgroup or multitude thereof; and any combination or multitude thereof; and ax. treats or prevents ulcerative colitis, inflammatory bowel disease, Crohn’s disease, checkpoint inhibitor colitis, as well as other gastrointestinal diseases and symptoms, liver disorders, including, for example, primary sclerosing cholangitis, non-alcoholicsteatohepatitis or non-alcoholic fatty liver disease, alcoholic hepatitis, or hepatic encephalopathy, metabolic disorders, including, for example, obesity, insulin resistance, or type 2 diabetes, oncology indications, including, for example, melanoma, renal cell carcinoma, bowel cancer and precancerous polyps, lymphoma, leukemia, myeloma, pancreatic cancer, breast cancer, lung cancer, testicular cancer, or sarcoma, cardiovascular disorders, including, for example, dyslipidaemia, atherosclerotic heart disease, or hypertension, immunological diseases, including, for example, type 1 diabetes, rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematous, or Sjogren’s disease, allergic and atopic disorders, including, for example, food allergy, anaphylaxis, atopic dermatitis, or atopic rhinitis or sinusitis, infectious diseases, including, for example, clostridioides difficile infection, multidrug resistant infection or colonisation, renal tract or urinary tract infections, blood stream infections, respiratory infections, or sepsis, neurological disorders, including for example, autism, multiple sclerosis, Parkinson’s disease, depression, anxiety, bipolar disorder, or schizophrenia.

[0311] In some embodiments, the composition is administered orally, colonically or rectally.

[0312] In some embodiments, said composition is administered to the patient using a dosing regimen selected from the group consisting of: hourly; every 2 hours; every 3 hours; every 4 hours; every 5 hours; every 6 hours; every 12 hours; once daily; twice daily; every 2 days; every 3 days; every 4 days; every 5 days; every 6 days; weekly; twice weekly; every 2 weeks; every 3 weeks; every 4 weeks; every 5 weeks; every 6 weeks; once monthly; twice monthly; every 2 months; every 3 months; every 4 months; every 5 months; every 6 months; yearly; twice yearly; every 2 years; every 3 years; every 4 years; and every 5 years.

[0313] Some embodiments provided herein relate to methods of promoting the growth of a member of a genus selected from the group consisting of: Acidaminococcaceae (family), Acidaminococcus, Adlercreutzia, Agathobaculum, Akkermansia, Alistipes, Alterileibacterium, Amedibacillus, Amedibacterium, Aminipila, Anaerobutyricum, Anaerococcus, Anaerocolumna, Anaerofustis, Anaerostipes, Anaerotignum, Anaerotruncus, Bacillus, Bacteroides, Barnesiella, Bifidobacterium, Bilophila, Blautia, Butyricimonas, Butyrivibrio, Campylobacter, Caproicibacter, Caproicibacterium, Caproiciproducens, Casaltella, Catenibacterium, Christensenella, Clostridium, Collinsella, Coprobacillus, Coprobacter, Coprococcus, Desulfovibrio, Dorea, Duodenibacillus, Dysosmobacter, Eggerthella, Enorma, Enterocloster, Enterococcus, Escherichia, Ethanoligenens, Eubacterium, Faecalibacillus, Faecalibacterium, Faecalibaculum, Finegoldia, Flavonifractor, Flintibacter, Fusicatenibacter, Gemmiger, Gordonibacter, Granulicatella, Herbinix, Holdemanella, Holdemania, Hoylesella, Hungatella, Intestinibacter, Intestinibaculum, Intestinimonas, Lachnoanaerobaculum, Lachnoclostridium, Lachnospira, Lachnospiraceae incertae sedis (unclassified rank, Lachnospiraceae family), Lacrimispora, Lactococcus, Ugilactobacillus, Longibaculum, Longicatena, Mageeibacillus, Maliibacterium, Marvinbryantia, Massilimicrobiota,Massiliprevotella, Massilistercora, Mediterraneibacter, Megamonas, Megasphaera, Merdibacter, Mesosutterella, Mitsuokella, Mogibacterium, Muribaculum, Negativibacillus, Novisyntrophococcus, Odoribacter, Olsenella, Oscillibacter, Oscillospiraceae (family), Oscillospiraceae incertae sedis (unclassified rank, Oscillospiraceae family), Parabacteroides, Paraclostridium, Paraprevotella, Parolsenella, Peptacetobacter, Peptoniphilus, Peptostreptococcus, Phascolarctobacterium, Phocaeicola, Porphyromonas, Prevotella, Pseudobutyrivibrio, Pusillibacter, Romboutsia, Roseburia, Ruminiclostridium, Ruminococcus, Ruthenibacterium, Schaalia, Segatella, Selenomonas, Sellimonas, Senegalimassilia, Slackia, Sodaliphilus, Solibaculum, Streptococcus, Subdoligranulum, Thomasclavelia, Tyzzerella, Veillonella, Vescimonas and any combination or multitude thereof, in the gastrointestinal tract of a subject, the method comprising the step of administering to a patient in need thereof, a composition disclosed herein.

[0314] Some embodiments provided herein relate to methods of decreasing the growth of a member of a genus selected from the group consisting of: Achromobacter, Acidaminococcus, Aeromonas, Alicyclobacillus, Bacteroides, Bifidobacterium, Blautia, Bosea, Burkholderiales, Clostridium, Cutibacterium, Desulfovibrio, Eggerthella, Enterobacter, Enterococcus, Escherichia, Eubacterium, Flavonifractor, Granulicatella, Hungatella, Klebsiella, Ugilactobacillus, Mediterraneibacter, Minicystis, Oscillibacter, Parabacteroides, Pluralibacter, Prevotella, Prosthecochloris, Pseudomonas, Rhodococcus, Salmonella, Schaalia, Serratia, Shewanella, Staphylococcus, Streptomyces, Sutterella, Veillonella, and any combination or multitude thereof, in the gastrointestinal tract of a subject, the method comprising the step of administering to a patient in need thereof, a composition disclosed herein.

[0315] Some embodiments provided herein relate to methods of preparing the composition of an embodiment of the disclosure, the method comprising culturing the microbial consortium of an embodiment of the disclosure.

[0316] In an example, a method of the disclosure relates to a method of co-culturing a community of microbial species, the method comprising:- selecting an inoculum disclosed herein and coculturing the inoculum under culture conditions.

[0317] In another example, a method of the disclosure relates to a method of co-culturing a community of microbial species, the method comprising:- selecting one or more keystone microbial strains from Table 13 and one or more core community microbial strains from Table 14 and coculturing the selection under culture conditions.

[0318] In another example, a method of the disclosure relates to a method of co-culturing a community of microbial species, the method comprising:- selecting microbial strains from Table 31 and coculturing the selection under culture conditions.

[0319] In another example, a method of the disclosure relates to a method of co-culturing a community of microbial species, the method comprising:- selecting microbial strains from Table 33 and coculturing the selection under culture conditions.

[0320] In another example, a method of the disclosure relates to a method of co-culturing a community of microbial species, the method comprising:- selecting microbial strains from Table 34 and coculturing the selection under culture conditions.

[0321] In another example, a method of the disclosure relates to a method of co-culturing a community of microbial species, the method comprising:- selecting microbial strains from Table 35 and coculturing the selection under culture conditions.

[0322] In an example, the method comprises selecting all microbial strains from Table 31 for coculturing under culture conditions. In another example, the method comprises selecting all microbial strains from Table 33 for coculturing under culture conditions. In another example, the method comprises selecting all microbial strains from Table 34 for coculturing under culture conditions. In another example, the method comprises selecting all microbial strains from Table 35 for coculturing under culture conditions.

[0323] In an example, the ratio of core community microbial strains to keystone microbial strains selected for co-culture under culture conditions is 10:1. In another example, the ratio is 5:1. In another example, the ratio is 3:1.

[0324] In other examples of methods disclosed herein, certain species are excluded from the co-culture. In an example, a co-culture excludes species from Pseudomonadota, Campylobacterota, and Fusobacteria, or any combination thereof. In another example, coculture excludes species selected from the group consisting of: Clostridium perfringens; Klebsiella pneumonia; Escherichia coli, Campylobacter jejuni; and Staphylococcus aureus.

[0325] In some embodiments, the consortium is cultured in a bioreactor with a capacity selected from the group consisting of: between 500ml and 1 L; between 1L and 10L; between 10L and 100L; between 100L and 1000L; between 1000L and 10,000L; between 10,000L and 100,000L; between 100,000L and 1,000,000L; between 1,000,000L 10,000,000L; and a value within a range defined by any two of the aforementioned values. For example, the bioreactor capacity may be >100L.

[0326] In some examples, the co-culture is mixed with individual monocultures of isolates. For example, a co-culture may be spiked with C. minuta and / or A. muciniphila. In other examples, the co-culture is supplemented with one or more additional microbial isolates, provided individually or in combination.

[0327] In an example, co-culture comprises a seed train. In another example, methods of co-culture may be performed under anaerobic conditions.

[0328] In an example, pH is controlled when performing methods of the disclosure. For example, pH of a culture may be controlled within a range of 5-9 or 6.5-7.5.

[0329] In certain examples methods of the disclosure may require separate cultures to be combined and subject to further culture expansion. For example, methods of the disclosure can require culturing the microbial strains in two or more bioreactors to prepare separate cocultures and combining the co-cultures to provide an intermediate. In an example, the intermediate is further cultured under culture conditions to provide a final product formulation.

[0330] In some embodiments, the bioreactor is adapted for continuous fermentation.

[0331] In some embodiments, a method of preparing the biotherapeutic composition of an embodiment of the disclosure, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

[0332] In some embodiments, a method of preparing the pharmaceutical composition of an embodiment of the disclosure, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

[0333] In some embodiments, a method of preparing the dosage form of an embodiment of the disclosure, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

[0334] In some embodiments, a method of co-culturing one or more core community microbial strains with one or more keystone microbial strains, comprising selecting one or more core community microbial strains selected from Table 14 and one or more keystone microbial strains selected from Table 13, and co-culturing the strains under suitable culture conditions.

[0335] In some embodiments, the co-culture comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from Table 14 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 13.

[0336] In some embodiments, the co-culture comprises 20 or more core community microbial strains selected from Table 14 and 10 or more keystone microbial strains selected from Table 13.

[0337] In other embodiments, the co-culture comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from Table 34 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 34. In other embodiments, the co-culture comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from Table 35 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 35.

[0338] In some embodiments, a method of estimating the minimum number of isolates required to achieve a desired level of functional potential or property in a microbial consortium or other complex community, said method comprising identifying the point on a rarefactioncurve where the model’s asymptote intersects with the benchmark functional potential or property.

[0339] In some embodiments, the method comprises the following steps:Step 1 - Isolate selection: Selecting a plurality of microbial isolates to comprise a target microbial community, wherein the isolates are representative of the genetic and functional diversity present within the community.Step 2 - Whole genome sequencing: Subjecting the selected microbial isolates to whole genome sequencing to obtain sequence data.Step 3 - Genome assembly and annotation: Assembling the obtained sequence data into complete or draft genomes for each isolate using a genome assembly pipeline, and subsequently annotating these genomes to identify functional gene categories, such as Clusters of Orthologous Genes (COGs) or equivalent functional annotations.Step 4 - Functional gene category identification: Identifying and cataloging the presence of functional gene categories within each genome based on the annotation results, wherein non-functional or non-essential categories, such as hypothetical proteins or tRNAs, are excluded from further analysis.Step 5 - Resampling and subset generation: Performing a resampling procedure on the annotated genomes, wherein subsets of isolates are randomly selected with replacement, covering a range of subset sizes from a single isolate to the total number of isolates in the community, to generate multiple iterations of isolate subsets.Step 6 - Functional potential assessment: For each subset generated in the resampling procedure, calculating the total number of unique functional gene categories present, thereby producing a dataset representing the functional potential or property of each subset size.Step 7 - Rarefaction curve construction: Constructing a rarefaction curve by plotting the number of unique functional gene categories against the number of isolates in each subset, wherein the curve depicts the relationship between the increasing number of isolates and the cumulative functional potential or property.Step 8 - Model fitting and asymptote determination: Fitting a mathematical model, such as a logistic or polynomial regression, to the rarefaction curve to determine the point at which the curve begins to asymptote, indicating a diminishing return in the discovery of new functional gene categories as additional isolates are added.Step 9 - Minimum viable consortium determination: Estimating the minimum number of isolates required to achieve a functional potential or property that meets or exceeds a predefined benchmark, such as the functional diversity present in a healthy or target microbial community, by identifying the point on the rarefaction curve where the model’s asymptote intersects with the benchmark functional potential or property.Step 10 - Application to therapeutic Design: Applying the results of the rarefaction analysis to design a minimal viable microbial consortium that retains the desired level of functional potential or property, ensuring that the consortium is both functionally robust and economically feasible for therapeutic applications.

[0340] Some embodiments provided herein relate to uses of the composition according to an embodiment of the disclosure in the manufacture of a medicament for a use selected from the group consisting of: reducing or preventing a medical disorder or disease associated with dysbiosis in a subject in need thereof; decreasing inflammation in a subject in need thereof; and decreasing dysbiosis in a subject.

[0341] Some embodiments provided herein relate to kits comprising the dosage form of an embodiment of the disclosure together with instructions for its use.

[0342] In some embodiments, the formulations include one or more microbes selected from one or more of the microbial phyla as set forth in Table 1. In alternative embodiments, any one or more (e.g., 1-5, 5-10, etc.) of the phyla, genera, species or strains identified in the tables provided herein are expressly excluded from the co-culture, the formulation to be administered, or both. One reason for such exclusion may be that such microbe has a deleterious effect on a particular disease state. In some embodiments, 50-95% (50-60, 60-70, 70-80, 80-95% and overlapping ranges therein), of the microbes are included, with the remaining 5-50% excluded.BY PHYLUM

[0343] Table 1 - By phylumIn some embodiments, formulations of the disclosure include one or more microbes selected from one or more of the microbial genera as set forth in Table 1. In alternative embodiments, any one or more (e.g., 1-5, 5-10, etc.) of the phyla, genera, species or strains identified in the tables provided herein are expressly excluded from the co-culture, the formulation to be administered, or both. One reason for such exclusion may be that such microbe has a deleterious effect on a particular disease state. In some embodiments, 50-95% (50-60, 60-70, 70-80, 80-95% and overlapping ranges therein), of the microbes are included, with the remaining 5-50% excluded.

[0344] Table 2 - By PhyumIn some embodiments, formulations of the disclosure include one or more microbes selected rom one or more of the microbial genera as set forth in Table 2.

[0345] Table 3 - By PhylumIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial phyla as set forth in Table 3.BY FAMILY

[0346] Table 4 - By familiesIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial families as set forth in Table 4.

[0347] Table 5 - By FamiliesIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial families as set forth in Table 5.

[0348] Table 6 - By FamiliesIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial families as set forth in Table 6.BY GENUS

[0349] Table 7 - By GeneraIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial genera as set forth in Table 7.

[0350] Table 8 - By GeneraIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial genera as set forth in Table 8.BY SPECIES

[0351] Table 9 - By SpeciesIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial species as set forth in Table 9.

[0352] Table 10 - By SpeciesIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial species as set forth in Table 10.

[0353] Table 11 - By SpeciesIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial species as set forth in Table 11.

[0354] Table 12 - Species of a further embodiment of the disclosureIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial species as set forth in Table 12.

[0355] In some embodiments, formulations of the disclosure include one or more core community microbial strains and one or more keystone microbial strains. For example, the formulations may include 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or 26 core community microbial strains, and 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 ,12,13, 14, 15, 16, 17, 18, 19, 20, 21 , or 22 keystone microbial strains. In some embodiments, the core community microbial strains are selected from the strains as set forth in Table 14. In some embodiments, the keystone microbial strains are selected from the strains as set forth in Table 13.

[0356] Table 13 - Microbial KeystonesIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial species as set forth in Table 13.

[0357] Table 14 - Microbial Core CommunityIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial species as set forth in Table 14.

[0358] As used herein, the terms “core community microbial strains” or “core community microbial species” refers to a foundational group of microbes that function together with one another, and together with keystone microbial strains, to restore, regenerate, improve, enhance, supplement, protect, stabilize, and / or boost a microbiome, such as a gut microbiome. In some embodiments, the core community microbial strains may maintain its communal function in the absence of any one strain or any few strains as set forth in Table 14. In some embodiments, an improved function takes place with the combination of the greatest number of strains as set forth in Table 14. In alternative embodiments, any one or more (e.g., 1-5, 5-10, etc.) of the phyla, genera, species or strains identified in Table 14 areexpressly excluded from the co-culture, the formulation to be administered, or both. One reason for such exclusion may be that such microbe has a deleterious effect on a particular disease state.

[0359] As used herein, the terms “keystone microbial strains” refers to microbes having an important role in survival, integration, and flourishment of other species in the compositions and formulations described herein. For example, a keystone microbial strain may play a role in survival of one or more core community microbial strains during culture of the microbial strains, during preparation of the formulations, during administration of the formulations, and / or during uptake of the microbial strains in a subject following administration. In some embodiments, the keystone microbial strains improve microbial growth, activity, survival, and / or proliferation of a microbial consortium in a bioreactor during culture. In some embodiments, the keystone microbial strains improve growth activity, survival, and / or proliferation of a microbial consortium in the gut of a subject. In some embodiments, the keystone microbial strains improve growth activity, survival, and / or proliferation of a microbial consortium both in a bioreactor and in the gut of a subject. In some embodiments, the keystone strains reduce the growth, activity, survival, and / or proliferation of pathogens or microbes that would otherwise negatively impact the core community strains. In some embodiments, the keystone strains perform one or more of the following: provide nutrients for the core community strains through for example metabolizing compounds into more digestible components, maintain a desired pH, serve as a prebiotic, serve as postbiotic, etc. In alternative embodiments, any one or more (e.g., 1-5, 5-10, etc.) of the phyla, genera, species or strains identified in Table 13 or 8 are expressly excluded from the co-culture, the formulation to be administered, or both. One reason for such exclusion may be that such microbe has a deleterious effect on a particular disease state.

[0360] In some embodiments, formulations of the disclosure comprise, consist of, or consist essentially of any 1 or more core community microbial strains as set forth in Table 14 and any 1 or more keystone microbial strains as set forth in Table 13; any 2 or more core community microbial strains as set forth in Table 14 and any 1 or more keystone microbial strains as set forth in Table 13; any 3 or more core community microbial strains as set forth in Table 14 and any 1 or more keystone microbial strains as set forth in Table 13; any 5 or more core community microbial strains as set forth in Table 14 and any 1 or more keystone microbial strains as set forth in Table 13; any 3 or more core community microbial strains as set forth in Table 14 and any 3 or more keystone microbial strains as set forth in Table 13; any 5 or more core community microbial strains as set forth in Table 14 and any 3 or more keystone microbial strains as set forth in Table 13; any 5 or more core community microbial strains as set forth in Table 14 and any 5 or more keystone microbial strains as set forth in Table 13; any 10 or more core community microbial strains as set forth in Table 14 and any 3 or more keystone microbial strains as set forth in Table 13; any 10 or more core community microbial strains as set forthin Table 14 and any 5 or more keystone microbial strains as set forth in Table 13; any 10 or more core community microbial strains as set forth in Table 14 and any 10 or more keystone microbial strains as set forth in Table 13; any 15 or more core community microbial strains as set forth in Table 14 and any 3 or more keystone microbial strains as set forth in Table 13; any 15 or more core community microbial strains as set forth in Table 14 and any 5 or more keystone microbial strains as set forth in Table 13; any 15 or more core community microbial strains as set forth in Table 14 and any 10 or more keystone microbial strains as set forth in Table 13; any 15 or more core community microbial strains as set forth in Table 14 and any 15 or more keystone microbial strains as set forth in Table 13; any 20 or more core community microbial strains as set forth in Table 14 and any 3 or more keystone microbial strains as set forth in Table 13; any 20 or more core community microbial strains as set forth in Table 14 and any 5 or more keystone microbial strains as set forth in Table 13; any 20 or more core community microbial strains as set forth in Table 14 and any 10 or more keystone microbial strains as set forth in Table 13; any 20 or more core community microbial strains as set forth in Table 14 and any 15 or more keystone microbial strains as set forth in Table 13; any 20 or more core community microbial strains as set forth in Table 14 and any 20 or more keystone microbial strains as set forth in Table 13; all core community microbial strains as set forth in Table 14 and any 3 or more keystone microbial strains as set forth in Table 13; all core community microbial strains as set forth in Table 14 and any 5 or more keystone microbial strains as set forth in Table 13; all core community microbial strains as set forth in Table 14 and any 10 or more keystone microbial strains as set forth in Table 13; all core community microbial strains as set forth in Table 14 and any 15 or more keystone microbial strains as set forth in Table 13; all core community microbial strains as set forth in Table 14 and any 20 or more keystone microbial strains as set forth in Table 13; all core community microbial strains as set forth in Table 14 and all keystone microbial strains as set forth in Table 13, or any number of core community microbial strains and any number of keystone microbial strains within a range described herein. In some embodiments, the formulations include any number of the core community microbial strains as set forth in Table 14 in combination with any number of the keystone microbial strains as set forth in Table 13.

[0361] In some embodiments, formulations of the disclosure include a ratio of core community microbial strains to keystone microbial strains. In some embodiments, the ratio of core community microbial strains to keystone microbial strains is in a ratio of 20: 1 , 15:1 : 10:1 , 9:1 , 8:1 , 7:1 , 6:1 , 5:1 , 4:1 , 3:1 , 2:1 , 1 : 1, 1 :2, 1 :3, 1 :4, 1 :5, 1 :6, 1 :7, 1 :8, 1:9, 1 :10, 1 : 15, or 1 :20 or at a ratio between any two of the aforementioned ratios. In some embodiments, the microbial strains in the formulations include a majority of core community microbial strains and a minority of keystone microbial strains. In some embodiments, the formulations include the core community microbial strains at a percentage of total microbial strains in an amount of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% or an amount withina range defined by any two of the aforementioned values. In some embodiments, the formulations include keystone microbial strains at a percentage of total microbial strains in an amount of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% or an amount within a range defined by any two of the aforementioned values. In some embodiments, the core community microbial strains are present in the formulation in an amount of 80% and the keystone microbial strains are present in the formulation in an amount of 20%. In some embodiments, the core community microbial strains are present in the formulation in an amount of 70% and the keystone microbial strains are present in the formulation in an amount of 30%. In some embodiments, the core community microbial strains are present in the formulation in an amount of 60% and the keystone microbial strains are present in the formulation in an amount of 40%. In some embodiments, the core community microbial strains are present in the formulation in an amount of 50% and the keystone microbial strains are present in the formulation in an amount of 50%. In some embodiments, the core community microbial strains are present in the formulation in an amount of 40% and the keystone microbial strains are present in the formulation in an amount of 60%. In some embodiments, the core community microbial strains are present in the formulation in an amount of 30% and the keystone microbial strains are present in the formulation in an amount of 70%. In some embodiments, the percentage of core community microbial strains and the percentage of keystone microbial strains are present at amounts within the percentages described herein.

[0362] Table 15 - Microbial Keystones and Core CommunityIn some embodiments, the composition of the disclosure includes one or more microbes selected from one or more of the microbial species as set forth in Table 15.

[0363] Table 16 - Microbial Keystones and Core Community taxa in a further embodiment

[0364] In some embodiments, the compositions or formulations of the disclosure include one or more microbes selected from Table 27 or Table 28.

[0365] “Keystone”, as discussed already above, refers to taxa identified in the literature which predicts microbiome recovery post antibiotic intervention. As used herein, the terms “keystone microbial strains” or “keystone species” refers to microbes having an important role in survival, integration, and flourishment of other species in the compositions and formulations described herein. For example, a keystone microbial strain may play a role in survival of one or more core community microbial strains during culture of the microbial strains, during preparation of the formulations, during administration of the formulations, and / or during uptake of the microbial strains in a subject following administration. In some embodiments, the keystone microbial strains improve microbial growth, activity, survival, and / or proliferation of a microbial consortium in a bioreactor during culture. In some embodiments, the keystone microbial strains improve growth activity, survival, and / or and proliferation of a microbial consortium in the gut of a subject. In some embodiments, the keystone microbial strains improve growth activity, survival, and / or and proliferation of a microbial consortium both in a bioreactor and in the gut of a subject. In some embodiments, the keystone strains reduce the growth, activity, survival, and / or proliferation of pathogens or microbes that would otherwise negatively impact the core community strains. In some embodiments, the keystone strains perform one or more of the following: provide nutrients for the core community strains through for example metabolizing compounds into more digestible components, maintain a desired pH, serve as a prebiotic, serve as postbiotic, etc. In alternative embodiments, any one or more (e.g., 1-5, 5-10, etc.) of the phyla, genera, species or strains identified in Table 29 or 14 are expressly excluded from the co-culture, the formulation to be administered, or both. One reason for such exclusion may be that such microbe has a deleterious effect on a particular disease state.

[0366] “Minimum core”, as discussed already above, refers to remaining taxa identified as preferentially important through analyses. For example, using the methods described in Example 6. As used herein, the terms “minimum core species”, “core community microbialstrains” or “core community microbial species” refers to a foundational group of microbes that function together with one another, and together with keystone microbial strains, to restore, regenerate, improve, enhance, supplement, protect, stabilize, and / or boost a microbiome, such as a gut microbiome. In some embodiments, the core community microbial strains may maintain its communal function in the absence of any one strain or any few strains as set forth in Tables 29 and 30. In some embodiments, an improved function takes place with the combination of the greatest number of strains as set forth in Table 30. In alternative embodiments, any one or more (e.g., 1-5, 5-10, etc.) of the phyla, genera, species or strains identified in Table 30 are expressly excluded from the co-culture, the formulation to be administered, or both. One reason for such exclusion may be that such microbe has a deleterious effect on a particular disease state.

[0367] In some embodiments, the compositions of the disclosure include one or more core community microbial strains and one or more keystone microbial strains. For example, the formulations may include 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or 26 core community microbial strains, and 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , or 22 keystone microbial strains. In some embodiments, the core community microbial strains are selected from the strains as set forth in Table 30. In some embodiments, the 5 keystone microbial strains are selected from the strains as set forth in Table 29.

[0368] Table 29 - Microbial Keystones

[0370] Table 31 - Microbial Keystones and Core Community currently represented in the 143 isolates comprising BB265

[0371] Table 32 - Microbial Keystones and Core Community taxa in a further embodiment

[0372] In some embodiments, the compositions or formulations of the disclosure comprise, consist of, or consist essentially of any 1 or more core community microbial strains as set forth in Table 30 and any 1 or more keystone microbial strains as set forth in Table 29; any 2 or more core community microbial strains as set forth in Table 30 and any 1 or more keystone microbial strains as set forth in Table 29; any 3 or more core community microbial strains as set forth in Table 30 and any 1 or more keystone microbial strains as set forth in Table 29; any 5 or more core community microbial strains as set forth in Table 30 and any 1 or more keystone microbial strains as set forth in Table 29; any 3 or more core community microbial strains as set forth in Table 30 and any 3 or more keystone microbial strains as set forth in Table 29; any 5 or more core community microbial strains as set forth in Table 30 and any 3 or more keystone microbial strains as set forth in Table 29; any 5 or more core community microbial strains as set forth in Table 30 and any 5 or more keystone microbial strains as set forth in Table 29; any 10 or more core community microbial strains as set forth in Table 30 and any 3 or more keystone microbial strains as set forth in Table 29; any 10 or more core community microbial strains as set forth in Table 30 and any 5 or more keystone microbial strains as set forth in Table 29; any 10 or more core community microbial strains as set forth in Table 30 and any 10 or more keystone microbial strains as set forth in Table 29; any 15 or more core community microbial strains as set forth in Table 30 and any 3 or more keystone microbial strains as set forth in Table 29; any 15 or more core community microbial strains as set forth in Table 30 and any 5 or more keystone microbial strains as set forth inTable 29; any 15 or more core community microbial strains as set forth in Table 30 and any 10 or more keystone microbial strains as set forth in Table 29; any 15 or more core community microbial strains as set forth in Table 30 and any 15 or more keystone microbial strains as set forth in Table 29; any 20 or more core community microbial strains as set forth in Table 30 and any 3 or more keystone microbial strains as set forth in Table 29; any 20 or more core community microbial strains as set forth in Table 30 and any 5 or more keystone microbial strains as set forth in Table 29; any 20 or more core community microbial strains as set forth in Table 30 and any 10 or more keystone microbial strains as set forth in Table 29; any 20 or more core community microbial strains as set forth in Table 30 and any 15 or more keystone microbial strains as set forth in Table 29; any 20 or more core community microbial strains as set forth in Table 30 and any 20 or more keystone microbial strains as set forth in Table 29; all core community microbial strains as set forth in Table 30 and any 3 or more keystone microbial strains as set forth in Table 29; all core community microbial strains as set forth in Table 30 and any 5 or more keystone microbial strains as set forth in Table 29; all core community microbial strains as set forth in Table 30 and any 10 or more keystone microbial strains as set forth in Table 29; all core community microbial strains as set forth in Table 30 and any 15 or more keystone microbial strains as set forth in Table 29; all core community microbial strains as set forth in Table 30 and any 20 or more keystone microbial strains as set forth in Table 29; all core community microbial strains as set forth in Table 30 and all keystone microbial strains as set forth in Table 29, or any number of core community microbial strains and any number of keystone microbial strains within a range described herein. In some embodiments, the compositions or formulations of the disclosure include any number of the core community microbial strains as set forth in Table 30 in combination with any number of the keystone microbial strains as set forth in Table 29.

[0373] In some embodiments, compositions or formulations of the disclosure include a ratio of core community microbial strains to keystone microbial strains. In some embodiments, the ratio of core community microbial strains to keystone microbial strains is in a ratio of 20:1 , 15:1 : 10:1 , 9:1 , 8:1 , 7:1 , 6: 1 , 5: 1 , 4: 1 , 3:1 , 2:1 , 1 :1 , 1 :2, 1 :3, 1 :4, 1:5, 1 :6, 1 :7, 1 :8, 1 :9, 1 :10, 1 : 15, or 1 :20 or at a ratio between any two of the aforementioned ratios. I n some embodiments, the microbial strains in the composition or formulation of the disclosure include a majority of core community microbial strains and a minority of keystone microbial strains. In some embodiments, the compositions or formulations of the disclosure include the core community microbial strains at a percentage of total microbial strains in an amount of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% or an amount within a range defined by any two of the aforementioned values. In some embodiments, the compositions or formulations of the disclosure include keystone microbial strains at a percentage of total microbial strains in an amount of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% or an amount within a range defined by any two of the aforementioned values.In some embodiments, the core community microbial strains are present in the composition or formulation of the disclosure in an amount of 80% and the keystone microbial strains are present in the composition or formulation of the disclosure in an amount of 20%. In some embodiments, the core community microbial strains are present in the composition or formulation of the disclosure in an amount of 70% and the keystone microbial strains are present in the formulation in an amount of 30%. In some embodiments, the core community microbial strains are present in the composition or formulation of the disclosure in an amount of 60% and the keystone microbial strains are present in the formulation in an amount of 40%. In some embodiments, the core community microbial strains are present in the composition or formulation of the disclosure in an amount of 50% and the keystone microbial strains are present in the composition or formulation of the disclosure in an amount of 50%. In some embodiments, the core community microbial strains are present in the composition or formulation of the disclosure in an amount of 40% and the keystone microbial strains are present in the composition or formulation of the disclosure in an amount of 60%. In some embodiments, the core community microbial strains are present in the composition or formulation of the disclosure in an amount of 30% and the keystone microbial strains are present in the composition or formulation of the disclosure in an amount of 70%. In some embodiments, the percentage of core community microbial strains and the percentage of keystone microbial strains are present at amounts within the percentages described herein.

[0374] Table 33 - Community of microbial species for culture expansionAnaerostipes hominisFaecalibacillus intestinalisAlistipes senegalensis

[0375] In an embodiment, the present disclosure relates to a culture expanded population of microbial species. In certain embodiments, the culture expanded population is defined by a starting population of microbial species, wherein the starting population is expanded under culture conditions. Accordingly, in an example, the present disclosure relates to a culture expanded population of microbial species, wherein the population of microbial species is culture expanded from a starting population of microbial species which comprises species selected from the species shown in Table 33. In an example, starting population comprises at least one core community microbial strains from the strains set forth in Table 33 and, at least one keystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least three core community microbial strains from the strains set forth in Table 33 and, at least one keystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least five core community microbial strains from the strains set forth in Table 33 and, at least one keystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least three core community microbial strains from the strains set forth in Table 33 and, at least three keystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least five core community microbial strains from the strains set forth in Table 33 and, at least three keystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least ten core community microbial strains from the strains set forth in Table 33 and, at least threekeystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least three core community microbial strains from the strains set forth in Table 33 and, at least five keystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least five core community microbial strains from the strains set forth in Table 33 and, at least five keystone microbial strains from the strains set forth in Table 33. In another example, starting population comprises at least ten core community microbial strains from the strains set forth in Table 33 and, at least five keystone microbial strains from the strains set forth in Table 33.

[0376] In another example, the culture expanded population of microbial species is culture expanded from a population of microbial species which comprises between 5 and 26 core community microbial strains from the strains set forth in Table 33 and, between 5 and 22 keystone microbial strains from the strains set forth in Table 33. In an example, the starting population consists of the microbial strains set forth in Table 33.

[0377] In other embodiments, the culture expanded population of microbial species is culture expanded from a population which comprises a specified ratio of core community microbial strains to keystone microbial strains, wherein the strains are selected from Table 33. For example, the ratio of core community microbial strains to keystone microbial strains can be 20:1. In another example, the ratio is 15:1. In another example, the ratio is 10:1. In another example, the ratio is 5:1. In another example, the ratio is 3:1 or 2: 1. In another example, the ratio is 1 :3. In another example, the ratio is 1 :5. In another example, the ratio is 1:10.

[0378] In another example, culture conditions comprises spiking with Christensenella minuta and / or Akkermansia muciniphila. In an example, culture conditions comprises spiking with C. minuta and A. muciniphila.

[0379] In another embodiment, the present disclosure relates to a culture expanded population of microbial species selected from Table 33. In an example, the culture expanded population comprises at least one core community microbial strains from the strains set forth in Table 33 and, at least one keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least three core community microbial strains from the strains set forth in Table 33 and, at least one keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least five core community microbial strains from the strains set forth in Table 33 and, at least one keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least three core community microbial strains from the strains set forth in Table 33 and, at least three keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least five core community microbial strains from the strains set forth in Table 33 and, at least three keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least ten core communitymicrobial strains from the strains set forth in Table 33 and, at least three keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least three core community microbial strains from the strains set forth in Table 33 and, at least five keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least five core community microbial strains from the strains set forth in Table 33 and, at least five keystone microbial strains from the strains set forth in Table 33. In another example, the culture expanded population comprises at least ten core community microbial strains from the strains set forth in Table 33 and, at least five keystone microbial strains from the strains set forth in Table 33.

[0380] In another example, the culture expanded population of microbial species is culture expanded from a population of microbial species which comprises between 5 and 26 core community microbial strains from the strains set forth in Table 33 and, between 5 and 22 keystone microbial strains from the strains set forth in Table 33. In an example, the starting population consists of the microbial strains set forth in Table 33.

[0381] In other embodiments, the culture expanded population of microbial species comprises a specified ratio of core community microbial strains to keystone microbial strains, wherein the strains are selected from Table 33. For example, the ratio of core community microbial strains to keystone microbial strains in the culture expanded population can be 20:1 . In another example, the ratio is 15: 1. In another example, the ratio is 10:1. In another example, the ratio is 5:1. In another example, the ratio is 3:1 or 2: 1. In another example, the ratio is 1 :3. In another example, the ratio is 1 :5. In another example, the ratio is 1:10.

[0382] In an example, the culture expanded population is provided in a formulation of the disclosure. In another example, the culture expanded population is provided in a cell culture. For example, the culture expanded population may be provided in a bioreactor culture. In an example, the culture expanded population is provided in a purified or partially purified bioreactor culture. In example, the culture expanded population is purified from the cell culture media in the bioreactor. For example, the culture expanded population may be purified via tangential flow filtration or centrifugation with an associated washing step.

[0383] Table 34 - Community of microbial species for culture expansion, optionally for use as an inoculum

[0384] In an embodiment, the present disclosure relates to a microbial community for culture expansion. Such communities can be culture expanded under culture conditions disclosed herein to provide formulations and compositions of the disclosure. In an example, the present disclosure relates to a culture expanded population of microbial species, wherein the population of microbial species is culture expanded from a starting population of microbial species which comprises species selected from the species shown in Table 34. In an example, the starting population comprises at least one core community microbial strains from the strains set forth in Table 34 and, at least one keystone microbial strains from the strains set forth in Table 34. In another example, the starting population comprises at least three core community microbial strains from the strains set forth in Table 34 and, at least one keystone microbial strains from the strains set forth in Table 34. In another example, the starting population comprises at least five core community microbial strains from the strains set forth in Table 34 and, at least one keystone microbial strains from the strains set forth in Table 34. In another example, the starting population comprises at least three core community microbialstrains from the strains set forth in Table 34 and, at least three keystone microbial strains from the strains set forth in Table 34. In another example, the starting population comprises at least five core community microbial strains from the strains set forth in Table 34 and, at least three keystone microbial strains from the strains set forth in Table 34. In another example, starting population comprises at least ten core community microbial strains from the strains set forth in Table 34 and, at least three keystone microbial strains from the strains set forth in Table 34. In another example, the starting population comprises at least three core community microbial strains from the strains set forth in Table 34 and, at least five keystone microbial strains from the strains set forth in Table 34. In another example, starting population comprises at least five core community microbial strains from the strains set forth in Table 34 and, at least five keystone microbial strains from the strains set forth in Table 34. In another example, the starting population comprises at least ten core community microbial strains from the strains set forth in Table 34 and, at least five keystone microbial strains from the strains set forth in Table 34.

[0385] In other embodiments, the culture expanded population of microbial species is culture expanded from a population which comprises a specified ratio of core community microbial strains to keystone microbial strains, wherein the strains are selected from Table 34. For example, the ratio of core community microbial strains to keystone microbial strains can be 20:1. In another example, the ratio is 15:1. In another example, the ratio is 10:1. In another example, the ratio is 5:1. In another example, the ratio is 3:1 or 2: 1. In another example, the ratio is 1 :3. In another example, the ratio is 1 :5. In another example, the ratio is 1:10.

[0386] In an example, the selected strains are characterized by their V3-V4 16S sequence as set forth by the relevant SEQ ID NO: in Table 34. In another example, the selected strains are characterized by their full length 16S sequence as set forth by the relevant SEQ ID NO: in Table 34.

[0387] In another example, culture conditions comprises spiking with Christensenella minuta and / or Akkermansia muciniphila. In an example, culture conditions comprises spiking with C. minuta and A. muciniphila. In an example, culture conditions comprises spiking with Ruminococcus spp..

[0388] In an example, the selected population is provided in a formulation of the disclosure.

[0389] In another example, the selected population is provided in a cell culture. For example, the culture expanded population may be provided in a bioreactor culture. In an example, the culture expanded population is provided in a purified or partially purified bioreactor culture. In an example, the selected population is an inoculum. In an example, the inoculum is for use in a first bioreactor. In another example, the inoculum is for use in a seed train.

[0390] Table 35 - Enlarged community of microbial species for culture expansion, optionally for use as an inoculum

[0391] In another example, the present disclosure relates to a culture expanded population of microbial species, wherein the population of microbial species is culture expanded from a starting population of microbial species which comprises species selected from the species shown in Table 35. In an example, the starting population comprises at least one core community microbial strains from the strains set forth in Table 35 and, at least one keystone microbial strains from the strains set forth in Table 35. In another example, the starting population comprises at least three core community microbial strains from the strainsset forth in Table 35 and, at least one keystone microbial strains from the strains set forth in Table 35. In another example, the starting population comprises at least five core community microbial strains from the strains set forth in Table 35 and, at least one keystone microbial strains from the strains set forth in Table 35. In another example, the starting population comprises at least three core community microbial strains from the strains set forth in Table 35 and, at least three keystone microbial strains from the strains set forth in Table 35. In another example, the starting population comprises at least five core community microbial strains from the strains set forth in Table 35 and, at least three keystone microbial strains from the strains set forth in Table 35. In another example, starting population comprises at least ten core community microbial strains from the strains set forth in Table 35 and, at least three keystone microbial strains from the strains set forth in Table 35. In another example, the starting population comprises at least three core community microbial strains from the strains set forth in Table 35 and, at least five keystone microbial strains from the strains set forth in Table 35. In another example, starting population comprises at least five core community microbial strains from the strains set forth in Table 35 and, at least five keystone microbial strains from the strains set forth in Table 35. In another example, the starting population comprises at least ten core community microbial strains from the strains set forth in Table 35 and, at least five keystone microbial strains from the strains set forth in Table 35.

[0392] In other embodiments, the culture expanded population of microbial species is culture expanded from a population which comprises a specified ratio of core community microbial strains to keystone microbial strains, wherein the strains are selected from Table 35. For example, the ratio of core community microbial strains to keystone microbial strains can be 20:1. In another example, the ratio is 15:1. In another example, the ratio is 10:1. In another example, the ratio is 5:1. In another example, the ratio is 3:1 or 2: 1. In another example, the ratio is 1 :3. In another example, the ratio is 1 :5. In another example, the ratio is 1:10.

[0393] In an example, the selected strains are characterized by their V3-V4 16S sequence as set forth by the relevant SEQ ID NO: in Table 35. In another example, the selected strains are characterized by their full length 16S sequence as set forth by the relevant SEQ ID NO: in Table 35.

[0394] In another example, culture conditions comprises spiking with Christensenella minuta and / or Akkermansia muciniphila. In an example, culture conditions comprises spiking with C. minuta and A. muciniphila.

[0395] In an example, the selected population is provided in a formulation of the disclosure. In another example, the selected population is provided in a cell culture. For example, the culture expanded population may be provided in a bioreactor culture. In an example, the culture expanded population is provided in a purified or partially purified bioreactor culture. In an example, the selected population is an inoculum. In an example, theinoculum is for use in a first bioreactor. In another example, the inoculum is for use in a seed train.

[0396] Table 36 - Culture expanded community of microbial species

[0397] In another embodiment, the present disclosure relates to a culture expanded population of microbial species selected from Table 36. In an example, the culture expanded population comprises at least one core community microbial strains from the strains set forth in Table 36 and, at least one keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least three core community microbial strains from the strains set forth in Table 36 and, at least one keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least five core community microbial strains from the strains set forth in Table 36 and, at least one keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least three core community microbial strains from the strains set forth in Table 36 and, at least three keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least five core community microbial strains from the strains set forth in Table 36 and, at least three keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least ten core community microbial strains from the strains set forth in Table 36 and, at least three keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least three core community microbial strains from the strains set forthin Table 36 and, at least five keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least five core community microbial strains from the strains set forth in Table 36 and, at least five keystone microbial strains from the strains set forth in Table 36. In another example, the culture expanded population comprises at least ten core community microbial strains from the strains set forth in Table 36 and, at least five keystone microbial strains from the strains set forth in Table 36.

[0398] In another example, the culture expanded population of microbial species comprises all of the microbial strains set forth in Table 36.

[0399] In an example, the culture expanded population is provided in a formulation of the disclosure. In another example, the culture expanded population is provided in a cell culture. For example, the culture expanded population may be provided in a bioreactor culture. In an example, the culture expanded population is provided in a purified or partially purified bioreactor culture. In example, the culture expanded population is purified from the cell culture media in the bioreactor. For example, the culture expanded population may be purified via tangential flow filtration or centrifugation with an associated washing step.

[0400] In an example, strains in the culture expanded population are characterized by their V3-V4 16S sequence as set forth by the relevant SEQ ID NO: in Table 36. In another example, the strains in the culture expanded population are characterized by their full length 16S sequence as set forth by the relevant SEQ ID NO: in Table 36.

[0401] In another example, the culture expanded population has been spiked with Christensenella minuta and / or Akkermansia muciniphila.

[0402] In a further aspect, the disclosure is a method for culturing a microbial co-culture, the method comprising: (a) cultivating a microbial co-culture in a first bioreactor having a first volume; (b) transferring at least a portion of the microbial co-culture from the first bioreactor into a second bioreactor having a second volume larger than the first volume; and (c) cultivating the microbial co-culture in the second bioreactor under conditions that maintain cell viability and / or diversity. In an example, the resulting viability is >50%. In another example, the resulting viability is >90%. In an example, the resulting diversity is >70%. In another example, the resulting diversity is >80%. In another example, the resulting diversity is >90%. In another example, the resulting diversity is >95%.

[0403] In some embodiments, steps (b) and (c) are repeated in one or more additional bioreactors of increasing volume, thereby forming a seed train for the microbial co-culture.

[0404] In an example, the microbial co-culture in a first bioreactor is an inoculum disclosed herein. In an example, the inoculum comprises the microbial strains shown in Table 31 or Table 33. In an example, the inoculum comprises the microbial strains shown in Table 34 or Table 35. In another example, the inoculum is obtained after culture expansion in the first bioreactor (i.e. it is an inoculum for the second bioreactor). In this example, the inoculum may be selected from the organisms provided in Table 34 or Table 35, as defined by eithertheir V3-V4 16S sequence or, their full length 16S sequence. In another example, the inoculum comprises the organisms provided in T able 34 or T able 35, as defined by either their V3-V4 16S sequence or, their full length 16S sequence.

[0405] In some embodiments, the first bioreactor has a volume selected from the group consisting of: approximately 1 L, 5 L, 20L, 150 L or greater.

[0406] In some embodiments, the second bioreactor has a volume selected from the group consisting of: approximately 150 L, 300 L, 2000 L, 5000 L or greater.

[0407] In some embodiments, the seed train process comprises at least two sequential bioreactor transfers, and wherein each subsequent bioreactor has a volume at least 2-fold larger than the preceding bioreactor. In an example, microbial diversity is maintained throughout the seed train process. In an example, the resulting diversity is >50%. In an example, the resulting diversity is >70%. In another example, the resulting diversity is >80%. In another example, the resulting diversity is >90%. In another example, the resulting diversity is >95%. In an example, at least two or three culture expanded compositions maintain at least 50% microbial diversity under culture conditions, wherein the culture expanded compositions are subsequently combined.

[0408] In some embodiments, the microbial co-culture comprises anaerobic microbes.

[0409] In some embodiments, the microbial co-culture is maintained in an anaerobic environment throughout the seed train process.

[0410] In some embodiments, the microbial co-culture retains at least 90% viability and maintains microbial diversity throughout the seed train process.

[0411] In some embodiments, the microbial co-culture retains at least a percentage viability selected from the group consisting of: 10-90%; 5-95%; 1-99%; 10%; 20%; 30%; 40%; 50%; 60%; 70%; 80%; 90%; 100%.

[0412] In some embodiments, the microbial co-culture is formulated for therapeutic application in human or animal microbiome restoration.

[0413] In some embodiments, the transfer between bioreactors is performed using aseptic techniques to prevent contamination and ensure culture integrity.

[0414] In other embodiments, the present disclosure relates to formulations comprising a culture expanded community of microbial species. For example, the formulation may comprise a community comprising core community microbial species and keystone microbial species, wherein the core community microbial species comprise members of at least the following genera: Dysosmobacter, Enterocloster, Ruthenibacterium, Vescimonas, Phocaeicola, Pusillimonas, Solibaculum, and Christensenella, and, wherein the keystone microbial species comprise members of at least the genus Phocaeicola, wherein the community is culture expanded under culture conditions and, wherein the formulation is formulated as a capsule, tablet or powder, preferably wherein the formulation comprises a non-naturally occurring pharmaceutically acceptable excipient. In an example, cultureconditions comprises spiking with C. minuta and / or A muciniphila. In another example, the community of microbial species in culture expanded using a seed train. In another example, the culture expanded community of microbial species is culture expanded from a population of microbial species which comprises 5 to 22 keystone microbial strains selected from Table 13 and 5 to 26 or more core community microbial strains selected from Table 14.

[0415] In an example, culture expanded compositions of the disclosure may be characterized based on the input species or strains used to produce it, as well as the species and strains in the culture expanded composition. For example, a composition of the disclosure may be culture expanded from a selection of species / strains from Table 34 or Table 35, wherein the culture expanded composition comprises a selection of species / strains from Table 36. In an example, a composition of the disclosure may be culture expanded from a selection of species / strains from Table 34 or Table 35, wherein the culture expanded composition comprises the species / strains from Table 36. In an example, a composition of the disclosure may be culture expanded from the species / strains in Table 34, wherein the culture expanded composition comprises the strains from Table 36. In an example, a composition of the disclosure may be culture expanded from the species / strains in Table 35, wherein the culture expanded composition comprises the strains from Table 36.Brief Description of the Drawings

[0416] Below is a brief description of each of the figures and drawings.

[0417] Figure 1 shows the diagrammatical representation of the processes that lead to ulcerative colitis induced by high levels of sulfide (either as a sulfide ion (S2-), a bifsulfide ion (SH_), or hydrogen sulfide (H2S)) and nitric oxide (NO).

[0418] Figure 2 shows a graphical representation of hydrogen competition between methanogens, acetogens and sulfate-reducing bacteria. Competition for hydrogen by methanogens and acetogens leads to a decrease in the activity and abundance of sulfate- reducing bacteria, resulting in decreased production of hydrogen sulfide.

[0419] Figure 3 shows the cysteine and methionine metabolic pathways which are directly related to sulfide production or consumption phenotype

[0420] Figure 4 shows the BB265 drug discovery process detailing lead selection and validation prior to consortium validation in a phase 1 study.

[0421] Figure 5 shows the taxa identified with the sulfide-consuming phenotype. All taxa listed showed a net decrease in sulfide concentration following incubation when compared to the negative control. Those taxa which showed a statistically significant reduction (p < 0.05) in sulfide concentration when compared to the negative control are indicated with an asterisk (*) preceding the Isolate ID.

[0422] Figures 6A and 6B show the average quantity of sulfide (H2S, S2', HS') consumed by microbial isolates identified to have a statistically significant sulfide consumer phenotyperelative to the negative control (medium only). Isolates were assayed in triplicate. Significance was determined by unpaired t-tests with Welch’s correction

[0423] Figure 7 shows the taxonomic IDs and lineages for a consortium. A ‘WGS’ sequence type infers that taxonomy was derived using Whole Genome Sequences. Taxonomy was determined by comparison to the Genome Taxonomy Database (release 220).

[0424] Figure 8 shows the clade tree for the cladistic groups comprising the 143 isolate consortium.

[0425] Figure 9 shows a pie chart displaying the abundance of annotated genes among metabolic pathway categories identified in the 143 isolate BB265 consortium.

[0426] Figure 10 shows the average reduction in aqueous sulfide (H2S, S2-, HS-) concentration in an ulcerative proctitis patient stool sample (Patient A) co-incubated with 127 isolates (see also Figure 20) comprising the BB265 complex consortium. Reduction in aqueous sulfide is displayed as change in concentrations (pM) from the negative control, which consists of stool incubated in media only. Individual consumer refers to ulcerative proctitis stool co-incubated with an individual top sulfide consumer isolate, which displayed 670 pM sulfide consumption when phenotyped individually. Significance was determined using Welch’s t-test. Mean ± SD.

[0427] Figure 11 shows the average reduction in aqueous sulfide (H2S, S2-, HS-) concentration in ulcerative proctitis patient stool samples (Patient A and C) co-incubated with the BB265 143-isolate consortium. Reduction in sulfide is displayed as change in concentration (pM) from the negative control, which consists of stool incubated in media only. Individual consumer refers to ulcerative proctitis stool co-incubated with the individual top sulfide consumer isolate, which displayed 670 pM sulfide consumption when phenotyped individually. Significance was determined using a Welch's t-test. Mean ± SD.

[0428] Figure 12 shows the colony forming units (CFU) determined over time when the 143 isolate BB265 consortium was co-cultured in bioreactors at three different volumetric scales: 1 L, 4 L and 20 L. CFU was assessed using data pooled from nine 1 L vessels, three 4 L vessels, and three 20 L vessels. Mean ± SD.

[0429] Figures 13A and 13B show the relative abundances of the 143 isolates comprising BB265 after co-culture in triplicate at 1 L scale.

[0430] Figures 14A and 14B show the relative abundances of the 143 isolates comprising BB265 after co-culture, comparing 1 L, 4 L, and 20 L bioreactor scales.

[0431] Figure 15 shows a rarefaction analysis used to estimate the functional redundancy within the BB265 consortium via a resampling procedure. The original 143 BB265 isolates were resampled with replacement for each subset of isolates ranging from 1 to 143. For each subset size (n), the total number of unique COG IDs annotated to the sampled isolates was counted. This resampling was repeated 50 times to account for variability. The resampled counts were plotted, resulting in a rarefaction curve. A model (y ~ log(x)) was fitted usingpolynomial regression, represented by a blue trend line on the plot. A golden horizontal line was drawn at 1677 COGs, representing the estimated number of COGs expected to be shared among FMT donor samples.

[0432] Figure 16 shows a schematic of the experimental design used to assess successful engraftment of the BB265 co-culture in a germ-free murine model.

[0433] Figure 17 shows the CFU determined from the feces of mice 2-weeks post receiving a second dose of the BB265 co-culture.

[0434] Figures 18A and 18B show the relative abundances of the 143 isolates comprising BB265 in the feces of mice at TO (pre-dose) and T2 (one-week post-dose) after treatment with the BB265 co-culture.

[0435] Figure 19 shows a matrix of correlation coefficients (R-sq) among TO (pre-dose) and T2 (one-week post-dose) post-dose samples of mice having been treated with the BB265 co-culture. Pearson correlations were calculated between the vectors of relative abundances for the included strains for each sample. Cells are color-coded by the strength of the correlation.

[0436] Figure 20 shows the taxonomic IDs and lineages for the 127 isolates as outlined in Example 4. A ‘WGS’ sequence type infers that taxonomy was derived using Whole Genome Sequences. Taxonomy was determined by comparison to the Genome Taxonomy Database (release 220).

[0437] Figures 21 A and 21 B show the presence of the 143 isolates comprising BB265 in the inoculum used to seed Bioreactor 1 , in Bioreactor 1 after fermentation at the time used as inoculum to seed Bioreactor 2, and in Bioreactor 2 after fermentation.Detailed Description of the Disclosure

[0438] For convenience, the following sections generally outline the various meanings of the terms used herein. Following this discussion, general aspects regarding compositions, formulations, use of medicaments and methods of the disclosure are discussed, followed by specific examples demonstrating the properties of various embodiments of the disclosure and how they can be employed. Headings and titles are for organizational purposes and should not be used to limit the disclosure or claims.

[0439] The embodiments described here also include equivalent variations and modifications other than those specifically described. Several embodiments also include all of the steps, features, formulations and compounds referred to or indicated in the specification, individually or collectively and any and all combinations or any two or more of the steps or features.

[0440] Each document, reference, patent application or patent cited in this text is expressly incorporated herein in their entirety by reference, which means that it should be read and considered by the reader as part of this text. That the document, reference, patentapplication or patent cited in this text is not repeated in this text is merely for reasons of conciseness. None of the cited material or the information contained in that material should, however, be understood to necessarily be common general knowledge.

[0441] Manufacturer’s instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated herein by reference, and can be employed in the practice of several embodiments of the disclosure.

[0442] The present disclosure is not to be limited in scope by any of the specific embodiments described herein. These embodiments are intended for the purpose of exemplification only. Functionally equivalent products, formulations and methods are clearly within the scope of the disclosure as described herein.1. DEFINITIONS

[0443] The meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail.

[0444] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean ±1 %.

[0445] The present disclosure describes various compositions comprising culture expanded communities of microbial species. These compositions can be provided as a population for use in various embodiments disclosed herein. For example, compositions of the disclosure can be formulated as required and, in this sense, may rather be described as a formulation. In other aspects, compositions of the disclosure may be used as an inoculum and, in this sense may be described as such.

[0446] “Therapeutically effective amount” as used herein with respect to methods of treatment and in particular drug dosage, shall mean that dosage that provides the specific pharmacological response for which the drug is administered in a significant number of subjects in need of such treatment. It is emphasized that “therapeutically effective amount,” administered to a particular subject in a particular instance will not always be effective in treating the diseases described herein, even though such dosage is deemed a “therapeutically effective amount” by those skilled in the art. It is to be further understood that drug dosages are, in particular instances, measured as oral dosages, or with reference to drug levels as measured in blood. Amounts effective for such a use will depend on: the desired therapeutic effect; the potency of the biologically active material; the desired duration of treatment; the stage and severity of the disease being treated; the weight and general state of health of thepatient; and the judgment of the prescribing physician. Treatment dosages need to be titrated to optimize safety and efficacy. One skilled in the art will appreciate that the appropriate dosage levels for treatment will thus vary depending, in part, upon the indication for which the active agent is being used, the route of administration, and the size (body weight, body surface or organ size) and condition (the age and general health) of the patient. Accordingly, the clinician may titre the dosage and modify the route of administration to obtain the optimal therapeutic effect. A typical dosage may range from about 0.1 mg / kg to up to about 100 mg / kg or more, depending on the factors mentioned above. In other embodiments, the dosage may range from 0.1 mg / kg up to about 100 mg / kg; or 1 mg / kg up to about 100 mg / kg; or 5 mg / kg up to about 100 mg / kg. The microbial concentration in the composition can be, for example, from 1 cfu / mL to 10 cfu / mL, from 100 cfu / mL to 1 thousand cfu / mL, from 10 thousand cfu / mL to 100 thousand cfu / mL, from 10 cfu / mL to 1 million cfu / mL, from 100 cfu / mL to 1 million cfu / mL, from 1 thousand cfu / mL to 1 million cfu / mL, from 10 thousand cfu / mL to 1 million cfu / mL, from 100 thousand cfu / mL to 1 million cfu / mL, from 1 million cfu / mL to 10 million cfu / mL, from 10 million cfu / mL to 100 billion cfu / mL, from 10 million to 50 million cfu / mL, for example from 50 million to 100 million cfu / mL, from 100 million to 500 million cfu / mL, from 500 million to 1 billion cfu / mL, from 1 billion to 5 billion cfu / mL, from 5 billion to 10 billion cfu / mL, from 10 billion to 15 billion cfu / mL, from 15 billion to 20 billion cfu / mL, from 20 billion to 25 billion cfu / mL, from 25 billion to 30 billion cfu / mL, from 30 billion to 35 billion cfu / mL, from 35 billion to 40 billion cfu / mL, from 40 billion to 45 billion cfu / mL, from 45 billion to 50 billion cfu / mL, from 50 billion to 55 billion cfu / mL, from 55 billion to 60 billion cfu / mL, from 60 billion to 65 billion cfu / mL, from 65 billion to 70 billion cfu / mL, from 70 billion to 75 billion cfu / mL, from 75 billion to 80 billion cfu / mL, from 80 billion to 85 billion cfu / mL, from 85 billion to 90 billion cfu / mL, from 90 billion to 95 billion cfu / mL, from 95 billion to 100 billion cfu / mL or an amount within a range defined by any two of the aforementioned values.

[0447] The frequency of dosing will depend upon the pharmacokinetic parameters of the active agent and the formulation used. Typically, a clinician will administer the composition until a dosage is reached that achieves the desired effect. The composition may therefore be administered as a single dose, or as two or more doses (which may or may not contain the same amount of the desired molecule or bioactive) over time, or as a continuous infusion via an implantation device, scope or catheter. Further refinement of the appropriate dosage is routinely made by those of ordinary skill in the art and is within the ambit of tasks routinely performed by them. Appropriate dosages may be ascertained through use of appropriate dose-response data.

[0448] As used herein, the term “microbial consortium” component can refer to a plurality of microbes.

[0449] As used herein, a “carrier” can be any solvents, diluents, excipients or other vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening oremulsifying agents, preservatives, solid binders, lubricants and the like, as suited to the particular dosage form desired. Such carrier may be natural or non-naturally occurring (e.g., partially or fully modified, synthetic, etc.).

[0450] As used herein, the term “pharmaceutically acceptable carrier” component can refer to a component that is not biologically or otherwise undesirable, for example, the component may be incorporated into a composition of the disclosure and administered to a subject as described herein without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the formulation in which it is contained. The component has generally met the required standards of toxicology and manufacturing.

[0451] As used herein the term “subject” generally includes mammals such as: humans; farm animals such as sheep, goats, pigs, cows, horses, llamas; companion animals such as dogs and cats; primates; birds, such as chickens, geese and ducks; fish; and reptiles. In some embodiments, the subject is human.

[0452] As used herein, the “gastrointestinal tract” refers to the tract from the mouth to the anus which includes all the organs of the digestive system such as the esophagus, stomach, pancreas, liver, gallbladder, small intestine (including the ileum), caecum, large intestine, colon and rectum. Strains of the disclosure are at least useful for conditions of the terminal ileum, caecum or rectum.

[0453] As used herein, a “non-inflammatory strain” refers to a strain which, when present in the gastrointestinal tract of a subject, for example a human, is associated with a noninflamed state.

[0454] As used herein, an “inflammatory strain” refers to a strain which, when present in the gastrointestinal tract of a subject, for example a human, is associated with an inflamed state.

[0455] The terms “species” and “strain”, as used herein, are not strictly separated from each other, and refer to a microbial entity which reproduces itself while being distinguishable from another species or strains. In some cases, microbial species and strains of the same species are well characterized. In particular in such situations, a strain may be considered as a subcategory of a species. A species is typically considered as a subcategory of a genus. In some cases, species and strains may be at the same taxonomic level, for example, refer to a subcategory of a genus. However, since prokaryotic taxonomy is rather flexible and conflicting, exceptions to those rules are possible. The taxonomic designation of a species or strain, as used herein, refers to all past, present and future taxon names, including all homotypic, heterotypic, subjective, objective, nomenclatural and invalid synonyms, along with misapplied names. In any case, based on common knowledge and state-of-the art taxonomic systems, the person skilled 20 in the art is able to clearly understand the taxonomic terms used herein. Moreover, with help of state-of-the art taxonomic systems and common general knowledgeregarding genotypic and phenotypic similarities, such as genotypic similarities, the person skilled in the art can readily judge whether two microbial species or strains are related, or closely related, or not. In particular, two species or strains may be considered to be related, when they share at least 1%, 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90%, e.g. at least 97%, of their 25 genome, and closely related when they share at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98% or 99%, for example in several embodiments at least 97%, of their genome. Furthermore, two subpopulations of a microbial species or strain are also considered closely related. The percentage of sharing two genomes refers, in particular, to the sequence similarity between said two genomes. For example, the sequence similarity in the context of two nucleic acid or sequences can refer to the residues in the two sequences which are the same when aligned by methods known in the art, and can take into consideration additions, deletions and substitutions. Moreover, the sequence similarity between microbial species or strains may be also judged as described in Patel (2001), Molecular Diagnosis 6(4) and Nguyen (2016), npj Biofilms and Microbiomes 2.

[0456] As used herein, the term “biotherapeutic” refers to a microorganism, such as bacterial isolate, that is useful for treating or preventing a disease or a condition, or provide a health benefit, in a subject.

[0457] The term “biotherapeutic composition” as used herein, refers to a formulation comprising a biotherapeutic preparation formulated together with one or more additional formulary ingredients to obtain a finished formulation suitable for delivery to a subject.

[0458] As used herein, the terms “treat,” “treating,” “treatment” and grammatical variations thereof mean subjecting an individual subject to a protocol, regimen, process or remedy, in which it is desired to obtain a physiologic response or outcome in that subject. Since every treated subject may not respond to a particular treatment protocol, regimen, process or remedy, treating does not require that the desired physiologic response or outcome be achieved in each and every subject or subject population. Accordingly, a given subject or subject population may fail to respond or respond inadequately to treatment.

[0459] As used herein, the term “prevent”, “prevented”, or “preventing” when used with respect to the treatment of mucosal inflammation in the gastrointestinal tract refers to a prophylactic treatment which increases the resistance of a subject to mucosal inflammation in the gastrointestinal tract, in other words, decreases the likelihood that the subject will develop mucosal inflammation in the gastrointestinal tract as well as a treatment after mucosal inflammation in the gastrointestinal tract has begun in order to fight the inflammation, e.g., reduce or eliminate it altogether or prevent it from becoming worse.

[0460] As used herein, the term “reducing”, or variations thereof refer to a reduction but not necessarily a complete abolition of gastrointestinal tract mucosal inflammation in a subject.

[0461] As used herein, the term “sample” refers to a collection of biological material obtained from a subject or a subject's surrounding environment. In some embodiments, thesample is obtained directly from the subject. For example, the sample can be a fecal sample or biopsy obtained during a colonoscopy. The sample may be in a form taken directly from the subject or surrounding environment, or it may be at least partially purified to remove at least some non-nucleic acid material. The purification may be slight, for instance amounting to no more than the concentration of the solids, or cells, of the sample into a smaller volume or the separation of cells from some or all of the remainder of the sample. In some embodiments, nucleic acids are isolated from the sample. Such isolated preparations include reverse transcription products and / or PCR amplification products of the nucleic acids in the sample. In some embodiments, the predominant nucleic acid is DNA or RNA. The nucleic acid preparations can be pure or partially purified nucleic acid preparations. Techniques for the isolation of nucleic acid from samples, including complex samples, are numerous and well known in the art.

[0462] The term “culture conditions” is used to refer to cells (e.g. a population or community of microorganisms) growing in culture. In an example, culture conditions refers to an actively dividing population of cells. Such cells may, in an example, be in exponential growth phase. In another example, such cells may be in stationary phase. In an example, culture conditions means culture in a bioreactor or, for example, via a seed train of the present disclosure.

[0463] In an example, culture conditions are anaerobic. In an example, anaerobiosis is achieved by continuously sparging a culture vessel with an anaerobic gas mixture to displace dissolved oxygen and maintain a reduced environment. Continuous sparging also maintains a slight positive pressure within the vessel to minimise oxygen intrusion from the external environment. In certain examples, the gas flow rate is maintained between 0.5 and 5 normal liters per minute, with the gas mixture comprising, for example, 5 % H2, 10 % CO2, and 85 % N2, or other anaerobic gas combinations. In the context of inoculation according to the disclosure, prior to inoculation, the relevant culture medium is reduced by sparging with 100 % N2until the redox potential is below -200 mV, and preferably at or below -350 mV.

[0464] Suitable temperature for culture conditions can be selected from the group consisting of: from 20°C to 45°C; 20°C; 21 °C; 22°C; 23°C; 24°C; 25°C; 26°C; 27°C; 28°C; 29°C; 30°C; 31 °C; 32°C; 33°C; 34°C; 35°C; 36°C; 37°C; 38°C; 39°C; 40°C; 41 °C; 42°C; 43°C; 44°C; and 45°C. In an example, the temperature is 37°C. Suitable time periods for the growth phase of culture conditions can be selected from the group consisting of: 12 to 48 hrs; 1 hr; 2 hrs; 3 hrs; 4 hrs; 5 hrs; 6 hrs; 7 hrs; 8 hrs; 9 hrs; 10 hrs; 11 hrs; 12 hrs; 13 hrs; 14 hrs; 15 hrs; 16 hrs; 17 hrs; 18 hrs; 19 hrs; 20 hrs; 21 hrs; 22 hrs; 231hrs; 24 hrs; 25 hrs; 26 hrs; 27 hrs; 28 hrs; 29 hrs; 30 hrs; 31 hrs; 32 hrs; 33 hrs; 34 hrs; 35 hrs; 36 hrs; 37 hrs; 38 hrs; 39 hrs; 40 hrs; 41 hrs; 42 hrs; 43 hrs; 44 hrs; 45 hrs; 46 hrs; 47 hrs; 48 hrs; 49 hrs; 50 hrs; 51 hrs; 52 hrs; 53 hrs; 54 hrs; 55 hrs; 56 hrs; 57 hrs; 58 hrs; 59 hrs; 60 hrs; 61 hrs; 62 hrs; 63 hrs; 64 hrs; 65 hrs; 66 hrs; 67 hrs; 68 hrs; 69 hrs; 70 hrs; 71 hrs; 72 hrs; 73 hrs; 74 hrs; 75 hrs; 76 hrs; 77 hrs;78 hrs; 79 hrs; 80 hrs; 81 hrs; 82 hrs; 83 hrs; 84 hrs; 85 hrs; 86 hrs; 87 hrs; 88 hrs; 89 hrs; 90 hrs; 91 hrs; 92 hrs; 93 hrs; 94 hrs; 95 hrs; and 96 hrs. In an example, a single bioreactor culture may involve culture for 18 - 36 hours. In the context of a seed train, for example, culture in a first bioreactor may involve culture for 6 - 24 hours and culture in a second bioreactor may involve culture for 24 - 36 hours.

[0465] In an example, inoculum of the disclosure may be provided to inoculate a bioreactor at a concentration selected from the group consisting of: 0.01-10% v / v; 0.01% v / v; 0.02% v / v; 0.03% v / v; 0.04% v / v; 0.05% v / v; 0.06% v / v; 0.07% v / v; 0.08% v / v; 0.09% v / v;0.10% v / v; 0.11% v / v; 0.12% v / v; 0.13% v / v; 0.14% v / v; 0.15% v / v; 0.16% v / v; 0.17% v / v;0.18% v / v; 0.19% v / v; 0.20% v / v; 0.21 % v / v; 0.22% v / v; 0.23% v / v; 0.24% v / v; 0.25% v / v;0.26% v / v; 0.27% v / v; 0.28% v / v; 0.29% v / v; 0.30% v / v; 0.31% v / v; 0.32% v / v; 0.33% v / v;0.34% v / v; 0.35% v / v; 0.36% v / v; 0.37% v / v; 0.38% v / v; 0.39% v / v; 0.40% v / v; 0.41% v / v;0.42% v / v; 0.43% v / v; 0.44% v / v; 0.45% v / v; 0.46% v / v; 0.47% v / v; 0.48% v / v; 0.49% v / v;0.50% v / v; 0.51% v / v; 0.52% v / v; 0.53% v / v; 0.54% v / v; 0.55% v / v; 0.56% v / v; 0.57% v / v;0.58% v / v; 0.59% v / v; 0.60% v / v; 0.61 % v / v; 0.62% v / v; 0.63% v / v; 0.64% v / v; 0.65% v / v;0.66% v / v; 0.67% v / v; 0.68% v / v; 0.69% v / v; 0.70% v / v; 0.71% v / v; 0.72% v / v; 0.73% v / v;0.74% v / v; 0.75% v / v; 0.76% v / v; 0.77% v / v; 0.78% v / v; 0.79% v / v; 0.80% v / v; 0.81% v / v;0.82% v / v; 0.83% v / v; 0.84% v / v; 0.85% v / v; 0.86% v / v; 0.87% v / v; 0.88% v / v; 0.89% v / v;0.90% v / v; 0.91% v / v; 0.92% v / v; 0.93% v / v; 0.94% v / v; 0.95% v / v; 0.96% v / v; 0.97% v / v;0.98% v / v; 0.99% v / v; 1.00%. 1.5% v / v; 2.0% v / v; 2.5% v / v; 3.0% v / v; 3.5% v / v; 4.0% v / v; 4.5% v / v; 5.0% v / v; 5.5% v / v; 6.0% v / v; 6.5% v / v; 7.0% v / v; 7.5% v / v; 8.0% v / v; 8.5% v / v; 9.0% v / v; 9.5% v / v; and 10.0% v / v.

[0466] Exemplary gas flow rates for anaerobic culture conditions may be selected from the group consisting of : 0.5 Ipm; 0.6 Ipm; 0.7 Ipm; 0.8 Ipm; 0.9 Ipm; 1.0 Ipm; 1.1 Ipm; 1.2 Ipm;1.3 Ipm; 1.4 Ipm; 1.5 Ipm; 1.6 Ipm; 1.7 Ipm; 1.8 Ipm; 1.9 Ipm; 2.0 Ipm; 2.1 Ipm; 2.2 Ipm; 2.3Ipm; 2.4 Ipm; 2.5 Ipm; 2.6 Ipm; 2.7 Ipm; 2.8 Ipm; 2.9 Ipm; 3.0 Ipm; 3.1 Ipm; 3.2 Ipm; 3.3 Ipm;3.4 Ipm; 3.5 Ipm; 3.6 Ipm; 3.7 Ipm; 3.8 Ipm; 3.9 Ipm; 4.0 Ipm; 4.1 Ipm; 4.2 Ipm; 4.3 Ipm; 4.4Ipm; 4.5 Ipm; 4.6 Ipm; 4.7 Ipm; 4.8 Ipm; 4.9 Ipm; 5.0 Ipm. In an example, gas flow can be maintained with mixtures including: H2, CO2, N2; or similar anaerobic combinations. In one example, the percentage of H2is selected from the group consisting of: 1 %; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 11 %; 12%; 13%; 14%; 15%; 16%; 17%; 18%; 19%; 20%; 21%; 22%; 23%; 24%; 25%; 26%; 27%; 28%; 29%; 30%; 31%; 32%; 33%; 34%; 35%; 36%; 37%; 38%;39%; 40%; 41%; 42%; 43%; 44%; 45%; 46%; 47%; 48%; 49%; 50%; 51 %; 52%; 53%; 54%;55%; 56%; 57%; 58%; 59%; 60%; 61%; 62%; 63%; 64%; 65%; 66%; 67%; 68%; 69%; 70%;71 %; 72%; 73%; 74%; 75%; 76%; 77%; 78%; 79%; 80%; 81%; 82%; 83%; 84%; 85%; 86%;87%; 88%; 89%; 90%; 91%; 92%; 93%; 94%; 95%; 96%; 97%; 98%; and 99%. In one example, the percentage of CO2is selected from the group consisting of: 1 %; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 11%; 12%; 13%; 14%; 15%; 16%; 17%; 18%; 19%; 20%; 21%;22%; 23%; 24%; 25%; 26%; 27%; 28%; 29%; 30%; 31%; 32%; 33%; 34%; 35%; 36%; 37%;38%; 39%; 40%; 41%; 42%; 43%; 44%; 45%; 46%; 47%; 48%; 49%; 50%; 51%; 52%; 53%;54%; 55%; 56%; 57%; 58%; 59%; 60%; 61%; 62%; 63%; 64%; 65%; 66%; 67%; 68%; 69%;70%; 71%; 72%; 73%; 74%; 75%; 76%; 77%; 78%; 79%; 80%; 81 %; 82%; 83%; 84%; 85%;86%; 87%; 88%; 89%; 90%; 91 %; 92%; 93%; 94%; 95%; 96%; 97%; 98%; and 99%. In one example, the percentage of N2is selected from the group consisting of: 1 %; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 11 %; 12%; 13%; 14%; 15%; 16%; 17%; 18%; 19%; 20%; 21%; 22%; 23%; 24%; 25%; 26%; 27%; 28%; 29%; 30%; 31%; 32%; 33%; 34%; 35%; 36%; 37%; 38%;39%; 40%; 41%; 42%; 43%; 44%; 45%; 46%; 47%; 48%; 49%; 50%; 51 %; 52%; 53%; 54%;55%; 56%; 57%; 58%; 59%; 60%; 61%; 62%; 63%; 64%; 65%; 66%; 67%; 68%; 69%; 70%;71 %; 72%; 73%; 74%; 75%; 76%; 77%; 78%; 79%; 80%; 81%; 82%; 83%; 84%; 85%; 86%;87%; 88%; 89%; 90%; 91 %; 92%; 93%; 94%; 95%; 96%; 97%; 98%; and 99%. In an example, the mixture is 5% H2; 10% CO2; 85% N2.

[0467] In certain examples, pH may be controlled within a range or at a value selected from the list selected from the group consisting of: 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14; 5-9; 6.5-7.5, with adjustments using HCI, acetic acid, formic acid, citric acid, lactic acid, sulfuric acid, nitric acid, phosphoric acid, NaOH, potassium hydroxide, calcium hydroxide, sodium bicarbonate, potassium bicarbonate, organic amines or ammonia. For example, pH may be between 6.8 and 7.2.

[0468] The term “culture expanded population” is used in the context of the present disclosure to refer to a population of cells (e.g. a population or community of microorganisms) that has been expanded under suitable culture conditions. Such conditions may include culture in a suitable vessel (e.g. a bioreactor) with suitable culture media to facilitate growth of the cells. One of skill in the art will appreciate that a culture expanded population may change over time for example, depending on the competitive nature of the cells in culture and / or the number of expansion steps. Accordingly, in certain examples, it may be appropriate to define the culture expanded population based on the starting population used to produce it (e.g. an inoculum). Alternatively, in other examples, it may be appropriate to define the culture expanded population based on one or more or all of its component part(s) (e.g. species). In an example, a culture expanded population of the disclosure is produced via seed train. For example, the seed train may comprise culture in at least two or three bioreactors. In an example, the seed train comprises between 2 and 5 bioreactors. In an example, the bioreactors in the seed train are of increasing volume. In an example, the seed train involves at least two or at least three bioreactors for culturing initial inoculums, with the culture expanded compositions (or portions thereof) from these bioreactors being combined to provide an inoculum for a seed train of the disclosure. For example, such an inoculum can used in a bioreactor of increasing volume to provide a further culture expanded composition.

[0469] The term “engraftment” refers to the ability of a formulation or population of the disclosure to establish in one or more niches of the gut of an animal and / or human. In certain examples, a formulation or population of the disclosure is “engrafted” if evidence of its establishment in the gastrointestinal tract, post-administration, can be obtained. In some embodiments, that evidence is obtained by molecular identification (e.g, Matrix- Assisted Laser Desorption / lonization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS), liquid chromatography -mass spectrometry (LC-MS), 16S rRNA sequencing, or genomic sequencing) of a sample obtained from the animal or human. Other examples of suitable methods include flow cytometry, qPCR / dPCR, biochemical identification. In an example, evidence is obtained by 16S sequencing, for example, sequencing one or more of SEQ ID NOs: 1 to 143 or 287 to 295 and / or SEQ ID Nos: 144 to 286 or 296 to 303. In some embodiments, the sample is a stool sample. In some embodiments, the sample is a biopsy sample taken from the gut (e.g, from a location along the gastrointestinal tract). In certain examples, engraftment may be transient. In some embodiments, transient engraftment means that the formulation or population of the disclosure can no longer be detected around 1 week, around 2 weeks, around 3 weeks or around 1 month after administration. In another example, transient engraftment means that formulation or population can no longer be directed around 2 or 3 or more months after administration. In an example, formulations or populations of the disclosure result in engraftment in a mouse following administration. In an example, the mouse is a germ free mouse. An example of assessing engraftment is shown in Figure 16. In other examples, formulations and populations of the disclosure result in engraftment in a human following administration.

[0470] The unit “cfu” refers to “colony forming unit”, which is the number of bacterial cells as revealed by microbiological counts on agar plates.

[0471] The term “sulfide” refers to molecular hydrogen sulfide (H2S) and its ions, including a bisulfide (HS_) ion and sulfide ion (S2') but may also include polysulfides (Sx2“), thiosulfate (S2O32“), elemental sulfur (S8), sulfite (SO32-) or sulfate (S042-).

[0472] Other definitions for selected terms used herein may be found within the detailed description of the disclosure and apply throughout. Unless otherwise defined, all other scientific and technical terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the disclosure belongs.

[0473] Where percentages are provided for agents, ingredients and compounds, they can be %m / m, %m / w, %w / w, %m / v, %v / v and variations thereof with respect to the formulation as a whole, unless otherwise indicated.

[0474] As used herein, the terms composition and formulation can be used interchangeably. Salt forms of the acids identified herein may be used instead of or in addition to the acid.

[0475] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean ±1 %.

[0476] Embodiments of the disclosure described herein may include one or more range of values (e.g. size, concentration etc.). A range of values will be understood to include all values within the range, including the values defining the range, and values adjacent to the range which lead to the same or substantially the same outcome as the values immediately adjacent to that value which defines the boundary to the range. For example, a 10% variation in upper or lower limits of a range can be totally appropriate and is encompassed by the disclosure. More particularly, the variation in the upper or lower limits of a range will be 5% or as is commonly recognized in the art, whichever is greater.

[0477] In this application, the use of the singular also includes the plural unless specifically stated otherwise. In this application, the use of “or” means “and / or” unless stated otherwise. Also, terms such as “element” or “component” encompass both elements and components comprising one unit and elements and components that comprise more than one subunit unless specifically stated otherwise. Also, the use of the term “portion” can include part of a moiety or the entire moiety.

[0478] Throughout this specification, unless the context requires otherwise, the word “comprise” or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

[0479] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (for example, bodies of the appended claims) are generally intended as “open” terms (for example, the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (for example, “a” and / or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. For example, “an” agentcan include one, two or several ingredients (and not necessarily a single ingredient). In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (for example, the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “ a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). It will be further understood by those within the art that any disjunctive word and / or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”

[0480] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0481] As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and sub-ranges and combinations of sub-ranges thereof. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into sub-ranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 articles refers to groups having 1 , 2, or 3 articles. Similarly, a group having 1-5 articles refers to groups having 1 , 2, 3, 4, or 5 articles, and so forth. The phrases “and ranges in between” can include ranges that fall in between the numerical values listed. For example, “1 , 2, 3, 10, and ranges in between” can include 1-10, 1-3, 2-10, etc.

[0482] While various aspects and embodiments have been disclosed herein, ...

Claims

CLAIMS1. A composition comprising a culture expanded community of microbial species, comprising:- a keystone microbial species selected from Table 13;- a plurality of core community microbial species selected from Table 14, wherein the keystone microbial species and the core community microbial species are culture expanded in co-culture under culture conditions.

2. The composition of claim 1 , which is a tablet, capsule or powder.

3. The composition of claim 1 , which is a microbial culture.

4. An inoculum for microbial culture, the inoculum comprising the composition of claim 1 or claim 3, preferably wherein the inoculum is a co-culture or portion thereof.

5. The composition according to any one of claims 1 to 3, wherein the composition is generated by co-culturing the core community microbial species and the keystone microbial species in a bioreactor.

6. The composition of claim 2, wherein the tablet, capsule or powder metabolizes hydrogen sulfide in the gastrointestinal tract of a subject post administration.

7. The composition of claim 1 , wherein the composition is lyophilized.

8. The composition of claim 2 or 7, wherein the composition comprises maltodextrin and inulin, preferably <12% inulin and <12% maltodextrin.

9. The composition according to any one of claims 2, 7 or 8, wherein the composition comprises a prebiotic.

10. The composition according to any one of claims 2 or 7 to 9, wherein the composition is encapsulated within an enteric coating.

11. The composition according to any one of claims 1 to 10, wherein the core community microbial species comprises at least one of the following species: Dysosmobacter welbionis, Enterocloster bolteae, Rut he ni bacterium lactatiformans, Vescimonas coprocola, Phocaeicolasalanitronis, Pusillimonas faecalis, Solibaculum mannosilyticum, Chrstensenella minuta, Alistipes magaguti, Parabacteroides goldsteinii, Alistipes communis, Ruminococcus bicirculans, Bacteroides caecimuris, Alistipes dispar, and Bacteroides salversiae.

12. The composition according to any one of claims 1 to 11 , wherein the keystone microbial species comprises at least one of the following species: Phocaeicola coprocola, Bifidobacterium bifidum, and Coprococcus catus.

13. The composition according to any one of claims 1 to 10, wherein the plurality of core community microbial species comprises at least one of the following species: Alistipes dispar, Bacteroides salyersiae, Bifidobacterium bifidum, Christensenella minuta, Coprococcus catus, Coprococcus spOO0154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis, Parabacteroides goldsteinii, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, and Vescimonas coprocola.

14. The composition according to any one of claims 1 to 13, wherein the composition comprises a ratio of core community microbial strains to keystone microbial strains of 10:1 , preferably 5:1 , more preferably 3:1.

15. The composition according to any one of claims 1 to 14, wherein the composition comprises between 50% to 80% core community microbial species, wherein the remaining % of microbial strains in the composition are keystone microbial species, preferably wherein the composition comprises between 50% to 80% core microbial strains, wherein the remaining % of microbial strains in the composition are keystone microbial strains.

16. A composition comprising a plurality of core community microbial species and, a plurality of keystone microbial species, wherein the composition comprises:- between 80 to 100% of the species identified on Tables 4 and 5;- between 80 to 100% of the species identified on Table 15;- between 80 to 100% of the species identified on Table 31 ; and / or- between 80 to 100% of the species identified on T able 33, T able 34, T able 35 or T able36.

17. The composition according to any one of claims 1 to 16, wherein the composition comprises:- between 80 to 100% of the strains identified in Table 15;- between 80 to 100% of the strains identified in Table 31 ;- between 80 to 100% of the species identified on T able 33, T able 34, T able 35 or T able36.

18. The composition according to any one of claims 1 to 17, wherein the microbial strains in the composition comprises core and keystone strains characterized by a V3-V4 16S sequence set forth in SEQ ID NO: 1 to 143 or 287 to 295, preferably wherein the composition comprises core and keystone strains characterised by a full length 16S sequences set forth in SEQ ID NOs: 144 to 286 or 296 to 303.

19. The composition according to any one of claims 1 to 17, wherein between 40 and 80% of the microbial strains in the composition are core and keystone strains characterized by a V3-V4 16S sequence set forth in SEQ ID NO: 1 to 143 or 287 to 295, preferably wherein between 60 and 80% of the core and keystone strains are characterised by a full length 16S sequences set forth in SEQ ID NOs: 144 to 286 or 296 to 303.

20. The composition according to any one of claims 1 to 19, where the composition does not comprise any bacteria from the phylum Pseudomonadota or Campylobacterota.21 . Use of the formulation of any one of claims 1 to 20 for the treatment of:- dysbiosis; or,- an inflammatory bowel disease (IBD), preferably wherein the IBD is ulcerative colitis, Crohn’s disease, gastroenteritis; colitis; or pouchitis.

22. A composition comprising a microbial consortium comprising at least one microbe, wherein the at least one microbe is selected from the group consisting of: bacteria and archaea; and wherein the at least one microbe is a member of a phylum, selected from the group consisting of: any one of the phyla listed in Table 1 ; any one of the phyla listed in Table 2; any one of the phyla listed in Table 3; and any combination, subgroup or multitude thereof, wherein the microbial consortium comprising a plurality of microbes, and wherein the microbe is a member of a species selected from the group consisting of: any one of the species listed in Table 9; any one of the species listed in Table 10; any one of the species listed in Table 11 ; any one of the species listed in Table 12; any one of the species listed in Table 13; any one of the species listed in Table 14; any one of the species listed in Table 15; and any one of the species listed in Table 16; and any combination, subgroup or multitude thereof; and wherein the composition comprises a plurality of core community microbial species, wherein said core community microbial species comprise members of at least the following genera: Dysosmobacter, Enterocloster, Ruthenibacterium, Vescimonas, Phocaeicola, Pusillimonas,Solibaculum, and Christensenella. a plurality of keystone microbial species, and wherein said keystone microbial species comprise members of at least the genus Phocaeicola.

23. A biotherapeutic composition comprising the composition of claim 22, together with an acceptable diluent or carrier.

24. A pharmaceutical composition comprising the composition of claim 22, together with a pharmaceutically acceptable diluent or carrier.

25. An isolated non-inflammatory strain of bacteria comprising a 16S ribosomal RNA (rRNA) gene having a nucleotide sequence selected from the group consisting of: SEQ ID NOs: 1 to 286.

26. A method of decreasing dysbiosis or inflammation in a subject in need thereof, said method comprising administering to the subject an effective amount of the composition according to any one of claims 1 to 20 or 22, the biotherapeutic of claim 23 or the pharmaceutical composition of claim 24.

27. A method of treating a disease or disorder associated with dysbiosis or inflammation in a subject in need thereof, said method comprising administering to the subject an effective amount of the composition according to any one of claims 1 to 20 or 22, the biotherapeutic of claim 23 or the pharmaceutical composition of claim 24.

28. A method of promoting the growth of a member of a genus selected from the group consisting of: Acidaminococcaceae (family), Acidaminococcus, Adlercreutzia, Agathobaculum, Akkermansia, Alistipes, Alterileibacterium, Amedibacillus, Amedibacterium, Aminipila, Anaerobutyricum, Anaerococcus, Anaerocolumna, Anaerofustis, Anaerostipes, Anaerotignum, Anaerotruncus, Bacillus, Bacteroides, Barnesiella, Bifidobacterium, Bilophila, Blautia, Butyricimonas, Butyrivibrio, Campylobacter, Caproicibacter, Caproicibacterium, Caproiciproducens, Casaltella, Catenibacterium, Christensenella, Clostridium, Collinsella, Coprobacillus, Coprobacter, Coprococcus, Desulfovibrio, Dorea, Duodenibacillus, Dysosmobacter, Eggerthella, Enorma, Enterocl oster, Enterococcus, Escherichia, Ethanoligenens, Eubacterium, Faecalibacillus, Faecalibacterium, Faecalibaculum, Finegoldia, Flavonifractor, Flintibacter, Fusicatenibacter, Gemmiger, Gordonibacter, Granulicatella, Herbinix, Holdemanella, Holdemania, Hoylesella, Hungatella, Intestinibacter, Intestinibaculum, Intestinimonas, Lachnoanaerobaculum, Lachnoclostridium, Lachnospira, Lachnospiraceae incertae sedis (unclassified rank, Lachnospiraceae family), Lacrimispora, Lactococcus, Ligilactobacillus, Longibaculum, Longicatena, Mageeibacillus, Maliibacterium,Marvinbryantia, Massilimicrobiota, Massiliprevotella, Massilistercora, Mediterraneibacter, Megamonas, Megasphaera, Merdibacter, Mesosutterella, Mitsuokella, Mogi bacterium, Muribaculum, Negativibacillus, Novisyntrophococcus, Odoribacter, Olsenella, Oscillibacter, Oscillospiraceae (family), Oscillospiraceae incertae sedis (unclassified rank, Oscillospiraceae family), Parabacteroides, Paraclostridium, Paraprevotella, Parolsenella, Peptacetobacter, Peptoniphilus, Peptostreptococcus, Phascolarctobacterium, Phocaeicola, Porphyromonas, Prevotella, Pseudobutyrivibrio, Pusillibacter, Romboutsia, Roseburia, Ruminiclostridium, Ruminococcus, Ruthenibacterium, Schaalia, Segatella, Selenomonas, Sellimonas, Senegalimassilia, Slackia, Sodaliphilus, Solibaculum, Streptococcus, Subdoligranulum, Thomasclavelia, Tyzzerella, Veillonella, Vescimonas and any combination or multitude thereof, in the gastrointestinal tract of a subject, the method comprising administering the subject an effective amount of the composition according to any one of claims 1 to 20 or 22, the biotherapeutic of claim 23 or the pharmaceutical composition of claim 24.

29. A method of decreasing the growth of a member of a genus selected from the group consisting of: Achromobacter, Acidaminococcus, Aeromonas, Alicyclobacillus, Bacteroides, Bifidobacterium, Blautia, Bosea, Burkholderiales, Clostridium, Cutibacterium, Desulfovibrio, Eggerthella, Enterobacter, Enterococcus, Escherichia, Eubacterium, Flavonifractor, Granulicatella, Hungatella, Klebsiella, Ligilactobacillus, Mediterraneibacter, Minicystis, Oscillibacter, Parabacteroides, Pluralibacter, Prevotella, Prosthecochloris, Pseudomonas, Rhodococcus, Salmonella, Schaalia, Serratia, Shewanella, Staphylococcus, Streptomyces, Sutterella, Veillonella, and any combination or multitude thereof, in the gastrointestinal tract of the subject, the method comprising administering the subject an effective amount of the composition according to any one of claims 1 to 20 or 22, the biotherapeutic of claim 23 or the pharmaceutical composition of claim 24.

30. A method of co-culturing a community of microbial species, the method comprising:- selecting the inoculum of claim 4,- selecting one or more keystone microbial strains from Table 13 and one or more core community microbial strains from Table 14;- selecting microbial strains from Table 31 ; or,- selecting microbial strains from Table 33, Table 34, Table 35 or Table 36, and co-culturing the selection under culture conditions.

31. A method of estimating the minimum number of isolates required to achieve a desired level of functional potential or property in a microbial consortium or other complex community, said method comprising identifying the point on a rarefaction curve where the model’s asymptote intersects with the benchmark functional potential or property.

32. The method of claim 30, wherein the method comprises selecting 3, 5, 10, 15, 20, or all strains from Table 31 , Table 33, Table 34, Table 35 or Table 36 and co-culturing the selected strains under culture conditions.

33. The method according to claim 30 or claim 32, wherein the ratio of core community microbial strains to keystone microbial strains selected for co-culture under culture conditions is 10:1 , preferably 5: 1 , more preferably 3:1.

34. The method according to any one of claims 30, 32 or 33, wherein the co-culture includes microbial isolates selected from the group consisting of: organisms from Firmicutes (Bacillota); Bacteroidetes (Bacteroidota); Actinobacteria (Actinomycetota); Verrucomicrobiota; and Pseudomonadota.

35. The method according to any one of claims 30 or 32 to 34, wherein co-culture excludes species from Pseudomonadota, Campylobacterota, and Fusobacteria, or any combination thereof, preferably wherein the co-culture exludes species selected from the group consisting of: Clostridium perfringens; Klebsiella pneumonia; Escherichia coli, Campylobacter jejuni; and Staphylococcus aureus.

36. The method according to any one of claims 30 to 35, wherein the culture conditions comprise using a large scale bioreactor, more preferably using a large scale bioreactor of greater than 100L, even more preferably, wherein the co-culture is spiked with C. minuta and / or A. muciniphila.

37. The method according to any one of claims 30 to 36, wherein culture conditions comprises a seed train.

38. The method of according to any one of claims 30 to 37, wherein the co-culture is cultured under anaerobic conditions.

39. The method according to any one of claims 30 to 38, wherein the pH of the culture is is controlled within a range of 5-9 or 6.5-7.5.

40. The method according to any one of claims 30 to 39, comprising culturing the microbial strains in two or more bioreactors to prepare separate co-cultures, combining the co-cultures to provide an intermediate, preferably wherein the intermediate is further cultured under culture conditions to provide a final product formulation.41 . A method for culturing a microbial co-culture, the method comprising: (a) cultivating a microbial co-culture in a first bioreactor having a first volume; (b) transferring at least a portion of the microbial co-culture from the first bioreactor into a second bioreactor having a second volume larger than the first volume; and (c) cultivating the microbial co-culture in the second bioreactor under conditions that maintain cell viability and / or diversity, preferably >50% viability, more preferably >90% viability.

42. The method of claim 41 , wherein steps (b) and (c) are repeated in one or more additional bioreactors of increasing volume, thereby forming a seed train for the microbial coculture.

43. The method of claim 41 or claim 42, wherein the microbial co-culture in a first bioreactor is the inoculum of claim 4 or an inoculum comprising the microbial strains shown in Table 31 , Table 33, Table 34 or Table 35.

44. The method according to any one of claims 41 to 43, wherein the first bioreactor has a volume selected from the group consisting of: approximately 1 L, 5 L, 20L, 150 L or greater, preferably wherein the second bioreactor has a volume selected from the group consisting of: approximately 150 L, 300 L, 2000 L, 5000 L or greater.

45. The method according to any one of claims 42 to 44, wherein the seed train comprises at least two sequential bioreactor transfers, and wherein each subsequent bioreactor has a volume at least 2-fold larger than the preceding bioreactor, preferably wherein the method maintains microbial diversity throughout the seed train process.

46. The method according to any one of claims 42 to 45, wherein the microbial co-culture is maintained in an anaerobic environment throughout the seed train process.

47. The method according to any one of claims 42 to 44, wherein the microbial co-culture is cryopreserved or lyophilised after final cultivation.

48. according to any one of claims 42 to 47, wherein the microbial co-culture is composed of at least two, three, four, or more distinct microbial species that remain in stable proportions throughout the seed train process.

49. A formulation comprising:- a culture expanded community of microbial species, wherein the community comprises core community microbial species and keystone microbial species, wherein the core community microbial species comprise members of at least the following genera: Dysosmobacter, Enterocloster, Ruthenibacterium, Vescimonas, Phocaeicola, Pusillimonas, Solibaculum, and Christensenella, and, wherein the keystone microbial species comprise members of at least the genus Phocaeicola, wherein the community is culture expanded under culture conditions and, wherein the formulation is formulated as a capsule, tablet or powder, preferably wherein the formulation comprises a non-naturally occurring pharmaceutically acceptable excipient.

50. The formulation of claim 49, wherein culture conditions comprises spiking with C. minuta and / or A. muciniphila.

51. The formulation of claim 49 or claim 50, wherein the culture expanded community of microbial species is culture expanded from a population of microbial species which comprises 5 to 22 keystone microbial strains selected from Table 13 and 5 to 26 or more core community microbial strains selected from Table 14.

52. The formulation according to any one of claims 49 to 51 , wherein the community of microbial species in culture expanded using a seed train.

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