Novel co-cultured microbial consortia

Abstract

The present invention relates 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.

Description

Novel Co-cultured Microbial ConsortiaCross Reference to Related Applications

[0001] This application claims the benefit of priority to Australian Provisional Patent Application No. 2023902607, filed August 16, 2023, the entire content of which is incorporated by reference herein.Incorporation by Reference of Material in Sequence Listing File

[0002] This application incorporates by reference the materials contained in the Sequence Listing XML file being submitted concurrently herewith: File name: SEQ LIST_WIPO_303386.xml, created on 07 August 2024 and is 433 bytes in size.Field

[0003] Embodiments of the present invention relates 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 of the present invention also relate to methods of treating medical disorders and pathologies by administering the composition to a patient in need thereof.Background

[0004] 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.

[0005] 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.

[0006] 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. It is an objective of the invention to overcome one or more problems foreshadowed by the prior art.Summary of the Invention

[0007] In several embodiments, a formulation comprising multiple core community microbial strains as well as multiple keystone microbial strains are provided to, for example, restore gut microbiome ecology. Advantageously in several embodiments, the core community and keystone strains are co-cultured together to provide a synergistic 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.

[0008] 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. The formulations are 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 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 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.

[0009] 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.

[0010] In several embodiments, a formulation 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 co-cultured, 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, the formulation in one embodiment 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, 10-15, 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 administration to a subject. In one embodiment, about 5-20% of strains that are in the co-culture are not significantly present in the formulation for administration to a subject.

[0011] In one embodiment, 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.

[0012] 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 Campylobacterotaare completely or significantly excluded or removed from the formulations.

[0013] 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, synergistic effects are achieved using the formulations described herein and other therapies such as pharmaceuticals.

[0014] 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 afterantibiotic 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 of the 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.

[0015] 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. Advantageously in several embodiments, the core community and keystone strains are co-cultured together to provide a synergistic 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.

[0016] 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 reduceadhesion 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 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.

[0017] 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.

[0018] 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, the composition in one embodiment 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, 10-15, 15-22 keystone strains (e.g., fromTable 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 but may not be present in the composition for administration to a subject. In one embodiment, about 5-20% of strains that are in the co-culture are not significantly present in the composition for administration to a subject.

[0019] In one embodiment, 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. 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.

[0020] 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.

[0021] 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 someembodiments, synergistic effects are achieved using the compositions described herein and other therapies such as pharmaceuticals.

[0022] 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 of the 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.

[0023] In a further embodiment, the invention 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.

[0024] In some embodiments, the microbial consortium comprises a plurality of microbes.

[0025] In some embodiments, the microbe is a member of a cladistic group selected from the groups consisting of: the cladistic groups presented in Figure 10 or any combination, subgroup or multitude thereof.

[0026] 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.

[0027] 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.

[0028] 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 1 1 ; 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.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] In some embodiments, the microbe is selected from the group consisting of: any one of the microbes presented and represented in Figure 6; Figure 7; Figure 9; and any combination, subgroup or multitude thereof.

[0034] In some embodiments, the microbial consortium is selected from the group consisting of: the consortium presented in Figure 6; the consortium presented in Figure 7; the consortium presented in Figure 9; and any combination, subgroup or multitude thereof.

[0035] 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 Figures 6 or 7; and any combination, subgroup or multitude thereof.

[0036] 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 for the 143 isolates presented in Figure 6 (SEQ ID NOs 1 to 143); any one of the full length 16S sequences for the 143 isolates presented in Figure 7 (SEQ ID NOs 144 to 286); and any combination, subgroup or multitude thereof.

[0037] In some embodiments, the sequence identity is selected from the any one of the groups 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% and at least 90%.

[0038] In some embodiments, the microbial consortium comprises any one of the communities presented in: Table 9; Table 10; Table 1 1 ; Table 12; Table 13; Table 14; Table 15; Table 16.

[0039] In some embodiments, the microbial consortium comprises at least the keystones presented in Table 13.

[0040] In some embodiments, the microbial consortium comprises at least the minimum core species presented in Table 14.

[0041] In some embodiments, the microbial consortium is the consortium of 143 members presented in Figure 9 (also known as BB265).

[0042] In some embodiments, the microbial consortium is the consortium of 127 members presented in Figure 22.

[0043] In some embodiments, the microbial consortium comprises a supportive community of microbial species, strains or isolates.

[0044] 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.

[0045] 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 lactatif ormans; Solibaculum mannosilyticum; and Vescimonas coprocola; and any combination, subgroup or multitude thereof.

[0046] 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, 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; and any combination, subgroup or multitude thereof.

[0047] 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 any combination, subgroup or multitude thereof.

[0048] In some embodiments, the plurality of keystone microbial species comprises: Phocaeicola coprocola; Bifidobacterium bifidum; and Coprococcus catus; and any combination, subgroup or multitude thereof.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] In some embodiments, the plurality of core community microbial species comrpises: 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: Phocaeicola coprocola; Bifidobacterium bifidum; and Coprococcus catus; and any combination, subgroup or multitude thereof.

[0053] In some embodiments, the microbial consortium the does not comprise any bacteria from the phylum Pseudomonadota or Campylobacterota.

[0054] In some embodiments, the microbial consortium the 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; Faecalibacterium 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; Ligilactobacillus ruminis; Marvinbryantia formatexigens; Mediterraneibacter gnavus; Megasphaera sp.; Mitsuokella multacida; Odoribacter splanchnicus; Oise ne I la uli; Oscillibacter sp.; Parabacteroides distasonis; Parabacteroides johnsonii; Parabacteroides merdae; Parabacteroides sp.; Peptacetobacter hiranonis; Phocaeicola coprocola; Phocaeicola coprophilus; Phocaeicola dorei; Phocaeicola plebeius; 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. .

[0055] In some embodiments, the microbial consortium is generated by co-culturing the minimum core species and the keystone species in a single bioreactor.

[0056] 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.

[0057] 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.

[0058] 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%.

[0059] In some embodiments, the microbial consortium comprises 3, 5, 10, 15, 20, or all core community microbial strains selected from T able 14 and 1 , 3, 5, 10, 15, 20, or all keystone microbial strains selected from Table 13.

[0060] 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, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , or all keystone species selected from Table 13.

[0061] 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.

[0062] 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.

[0063] In some embodiments, the microbial consortium comprises between 1 to 1000 microbial species, strains or isolates.

[0064] 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; 1 1 ; 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; 1 10; 111 ; 112; 1 13; 114; 115; 116; 117; 1 18; 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.

[0065] In some embodiments, the microbial consortium comprises between 500 to 1000 microbial species, strains or isolates.

[0066] In some embodiments, the microbial consortium comprises between 200 to 500 microbial species, strains or isolates.

[0067] In some embodiments, the microbial consortium comprises between 20 to 200 microbial species, strains or isolates.

[0068] In some embodiments, the microbial consortium comprises between 130 to 140 microbial species, strains or isolates.

[0069] In some embodiments, the microbial consortium comprises between 120 to 130 microbial species, strains or isolates.

[0070] In some embodiments, the microbial consortium comprises between 110 to 120 microbial species, strains or isolates.

[0071] In some embodiments, the microbial consortium comprises between 100 to 110 microbial species, strains or isolates.

[0072] In some embodiments, the microbial consortium comprises between 80 to 90 microbial species, strains or isolates.

[0073] In some embodiments, the microbial consortium comprises between 70 to 80 microbial species, strains or isolates.

[0074] In some embodiments, the microbial consortium comprises between 10 to 70 microbial species, strains or isolates.

[0075] In some embodiments, the microbial consortium comprises between 10 to 60 microbial species, strains or isolates.

[0076] In some embodiments, the microbial consortium comprises between 10 to 50 microbial species, strains or isolates.

[0077] In some embodiments, the microbial consortium comprises between 5 to 20 microbial species, strains or isolates.

[0078] In some embodiments, the microbial consortium comprises between 5 to 15 microbial species, strains or isolates.

[0079] In some embodiments, the microbial consortium comprises between 1 to 10 microbial species, strains or isolates.

[0080] In some embodiments, the microbial consortium comprises between 1 to 5 microbial species, strains or isolates.

[0081] In some embodiments, the microbial consortium comprises 143 microbial species, strains or isolates.

[0082] In some embodiments, the microbial consortium comprises 127 microbial species, strains or isolates.

[0083] 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.

[0084] 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.

[0085] 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:

[0086] 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.

[0087] Step 2 - Whole genome sequencing: Subjecting the selected microbial isolates to whole genome sequencing to obtain sequence data.

[0088] 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.

[0089] 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.

[0090] 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.

[0091] 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.

[0092] 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.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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 Figure 6; Figure 7; and Figure 9; 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 Figure 6; Figure 7; and Figure 9; or any combination, subgroup or multitude thereof.

[0097] 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 T able 9; Table 10; Table 1 1 ; 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 1 1 ; Table 12; Table 13; Table 14; Table 15; Table 16; or any combination, subgroup or multitude thereof.

[0098] 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:

[0099] a. carbohydrate metabolism, including; glycolysis / gluconeogenesis, the citrate cycle, the pentose phosphate pathway, fructose and mannose metabolism, galactosemetabolism, ascorbate and aldarate metabolism, starch and sucrose metabolism, inositol phosphate metabolism, and pyruvate metabolism;

[0100] b. lipid metabolism, including; fatty acid biosynthesis, fatty acid degradation, steroid biosynthesis and bile acid biosynthesis;

[0101] 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; and

[0102] d. vitamin / 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.

[0103] 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 33; and any combination or multitude thereof.

[0104] 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 33; and any combination or multitude thereof.

[0105] 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 34; and any combination, subgroup or multitude thereof.

[0106] 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 35; and any combination, subgroup or multitude thereof.

[0107] 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 36; and any combination, subgroup or multitude thereof.

[0108] 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 metaboliclesion; 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; 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.

[0109] In some embodiments, certain strains in the co-culture and / or formulation for administration to a subject are selected based on these phenotypes.

[0110] In some embodiments, the composition demonstrates a property selected from any one of the groups consisting of:[0011 1] a. emergent metabolic functions;

[0112] 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;

[0113] 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;

[0114] 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;

[0115] 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));

[0116] f. synergistic metabolic functions relating to: short-chain fatty acids (SCFAs); sulfide homeostasis; energy harvest; tryptophan metabolism; bile acid metabolism; vitamin production; drug metabolism;

[0117] g. reduces sulfide and nitric oxide load on epithelial cells which leads to a metabolic lesion via inhibition of cellular respiration;

[0118] h. reduces relative abundance and or metabolic activity of sulfidogenic microbiota in vitro;

[0119] 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;

[0120] j. reduces sulfide levels in vitro via metabolic substrate competition;

[0121] k. reduces sulfide levels in vitro by consuming hydrogen;

[0122] I. reduces relative abundance and or metabolic activity of sulfidogenic microbiota;

[0123] m. reduce 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;

[0124] 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;

[0125] o. induces colonocyte apoptosis in lesions to break an induced stable inflammatory state driven;

[0126] p. drives down undesired inflammation;

[0127] q. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host protease activity;

[0128] r. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host protease activity;

[0129] s. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial protease activity;

[0130] t. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing microbial protease activity;

[0131] u. reduces sulfide (production in the colon by modulating host protease activity;

[0132] v. reduces sulfide production in the colon by reducing host protease activity;

[0133] w. reduces sulfide production in the colon by modulating microbial protease activity;

[0134] x. reduces sulfide production in the colon by reducing microbial protease activity;

[0135] y. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host antiprotease (protease inhibitor) activity;

[0136] z. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host antiprotease (protease inhibitor) activity;

[0137] aa. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial antiprotease (protease inhibitor) activity;

[0138] ab. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine)

[0139] ac. into the colon by reducing microbial antiprotease (protease inhibitor) activity;

[0140] ad. reduces sulfide production in the colon by modulating host antiprotease (protease inhibitor) activity;

[0141] ae. reduces sulfide production in the colon by reducing host antiprotease (protease inhibitor) activity;

[0142] af. reduces sulfide production in the colon by modulating microbial antiprotease (protease inhibitor) activity;

[0143] ag. reduces sulfide production in the colon by reducing microbial antiprotease (protease inhibitor) activity;

[0144] 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;

[0145] ai. decreases inflammation in the subject;

[0146] aj. decreases inflammation in the subject when measured by a parameter selected from the group consisting of: TNFa signaling via NF-KB; I FNO signaling; IFNy signaling; IL6 JAK STAT3 signaling; activation of pro-apoptotic pathways; initiation of unfolded protein response;

[0147] 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 ;

[0148] al. treats and / or prevents dysbiosis;

[0149] am. treats or prevents a medical disorder or disease associated with dysbiosis;

[0150] an. treats or prevents a medical disorder or disease associated with mycobiome dysbiosis;

[0151] ao. treats and / or prevents a gastrointestinal disorder;

[0152] 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;

[0153] aq. treats and / or prevents gastrointestinal tract mucosal inflammation;

[0154] 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;

[0155] as. treats and / or prevents inflammatory bowel disease;

[0156] at. treats and / or prevents ulcerative colitis; Crohn's disease; gastroenteritis; colitis; checkpoint inhibitor colitis; and pouchitis;

[0157] 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;

[0158] 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, Alterileibacterium, Amedibacillus, Amedibacterium, Aminipila, Anaerobutyricum, Anaerococcus, Anaerocolumna, Anaerofustis, Anaerostipes, Anaerotignum, Anaerotruncus, Bacillus, Bacteroides, Bamesiella, 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, Ligilactobacillus, 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 and Vescimonas or any combination, subgroup or multitude thereof;

[0159] 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

[0160] 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.

[0161] In some embodiments, certain strains in the co-culture and / or formulation for administration to a subject are selected based on these properties.

[0162] In some embodiments, in combination with an therapy or active agent specific to the one or more diseases or disorders.

[0163] In some embodiments, the microbe is a fecal or colonic bacteria.

[0164] In some embodiments, the microbe is non-inflammatory.

[0165] In some embodiments, the microbe is cultured from a fecal or colonic biopsy sample.

[0166] In some embodiments, the microbial consortium comprises a community of microbes derived from a stool or biopsy of one or more human donors.

[0167] In some embodiments, the human donor is a healthy donor.

[0168] In some embodiments, the human donor is not an un-healthy donor.

[0169] In some embodiments, the human donor is not a donor presenting the underlying disease state.

[0170] In some embodiments, the community of microbes is not an inoculum.

[0171] In some embodiments, the community of microbes is cultured microbes produced from a bioreactor.

[0172] In some embodiments, the community of microbes is cultured microbes produced from a single bioreactor.

[0173] In some embodiments, the community of microbes is cultured microbes produced from a single continuous bioreactor.

[0174] In some embodiments, the community of microbes is cultured microbes produced from 1 to 10 bioreactors.

[0175] 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.

[0176] In some embodiments, the community of microbes is cultured microbes produced from 1 to 10 continuous bioreactors.

[0177] 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.

[0178] In some embodiments, the community of microbes has a metabolic profile which is indicative of a community of microbes produced from a bioreactor fermentation.

[0179] 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.

[0180] 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).

[0181] 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.

[0182] 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.

[0183] 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.

[0184] 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.

[0185] 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.

[0186] 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.

[0187] 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.

[0188] 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.

[0189] 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.

[0190] 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.

[0191] 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.

[0192] 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.

[0193] 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.

[0194] 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.

[0195] In some embodiments, the cell count density (OD) which is indicative of a community of microbes produced from a bioreactor fermentation is 5.0.

[0196] 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.

[0197] In some embodiments, the cultured microbes are derived from multiple of human donors.

[0198] In some embodiments, the community of microbes comprises uncultured microbes.

[0199] In some embodiments, the uncultured microbes are derived from a single human donor.

[0200] In some embodiments, the composition is a fecal transplant microbiota composition.

[0201] In some embodiments, the community of microbes comprise microbes which lack lytic phage.

[0202] 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.

[0203] 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%; atleast 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 1 1%; at least 10.5%; at least 10%; and a value within a range defined by any two of the aforementioned values.

[0204] In some embodiments, the microbes are selected using the following criteria: 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 least79.5%; 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 1 1%; at least 10.5%; a at least 10% and a value within a range defined by any two of the aforementioned values.

[0205] In some embodiments, the composition is lyophilized.

[0206] In some embodiments, the composition is a liquid.

[0207] 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.

[0208] 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 viability immediately 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 least80.5%; 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.

[0209] 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.

[0210] In some embodiments, the composition comprises a prebiotic.[0021 1] In some embodiments, the composition comprises a carrier.

[0212] In some embodiments, the composition comprises an insoluble fibre, a buffer, an osmotic agent, an antifoaming agent, and / or a preservative.

[0213] In some embodiments, the composition comprises a chemostat medium.

[0214] In some embodiments, the composition comprises a saline composition.

[0215] In some embodiments, the composition comprises a resistant starch.

[0216] In some embodiments, the composition is lyophilized with pharmaceutically acceptable excipients.

[0217] In some embodiments, the composition comprises a stabiliser and / or cryoprotectant.

[0218] 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.).

[0219] 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; and any combination or multitude thereof.

[0220] 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.

[0221] 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.

[0222] 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.

[0223] 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.

[0224] In some embodiments, said cryoprotectant is trehalose at a concentration of at least 5% in said lyophilized formulation.

[0225] In some embodiments, said cryoprotectant is trehalose at a concentration of at least 10% in said lyophilized formulation.

[0226] In some embodiments, said composition is a pharmaceutical composition.

[0227] In some embodiments, the at least one strain of bacteria is diluted with an inert powdered diluent.

[0228] In some embodiments, said composition comprises one or more pharmaceutically acceptable carriers or excipients.

[0229] In some embodiments, said composition is formulated as a geltab, pill, enema, microcapsule, capsule, powder, caplet, or tablet.

[0230] In some embodiments, the capsule or tablet is enteric-coated, pH dependent, slow-release, and / or gastro-resistant.

[0231] In some embodiments, the composition is adapted for administration orally, colonically or rectally.

[0232] 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.

[0233] In some embodiments, the composition comprises a pharmacologically active dose of bacteria cells or spores selected from the group consisting of: 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.

[0234] In some embodiments, a single dosage form, such as a single capsule, tablet, pill, or powder, includes an amount of bacterial cells ranging from 1 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.

[0235] 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.

[0236] 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. wherein the formulations or compositions comprise is 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, 1 1 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.

[0237] 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 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, or 10,000 L, or an amount within a range defined by any two of the aforementioned values.

[0238] 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.

[0239] In some embodiments, precision therapeutics are provided wherein the formulation is altered based on sex, ethnicity, disease sub-types, diet, age, etc.

[0240] In some embodiments, personalized formulations may also be provided that are individualized to a patient.

[0241] 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.

[0242] 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.)

[0243] 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.

[0244] 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 %.

[0245] 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 metaboliteproduced 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) 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 (UDCA).

[0246] 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.

[0247] 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.

[0248] 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 (UDCA).

[0249] 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.

[0250] 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- 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 (UDCA).

[0251] 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 (UDCA).

[0252] 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.

[0253] 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 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 (UDCA).

[0254] 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 andH2, 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 (UDCA).

[0255] 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 (UDCA).

[0256] 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 (UDCA).

[0257] 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.

[0258] 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.

[0259] 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.

[0260] 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 sulphide levels in the colon of a patient in need thereof; sulphide consumption; reducing sulphide and nitric oxide load on epithelial cells which affects cell respiration leading to a metabolic lesion; reducing relative abundance and or metabolic activityof sulfidogenic microbiota; reducing sulphide levels in the colon directly through consumption / assimilation; reducing sulphide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by metabolic substrate competition; reducing sulphide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by diverting metabolic substrates away from the production of sulphide; reducing sulphide levels, relative abundance and or metabolic activity of sulfidogenic microbiota in the colon by consuming H2; reducing sulphide levels, relative abundance and or metabolic activity of sulfidogenic microbiota by reducing release of metabolizable sulfur substrates; reducing sulphide 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.

[0261] In some embodiments, the microbial consortium comprises microbes that comprise a gene that is responsible for the phenotype of sulfide consumption.

[0262] 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 sulphide (H2S).

[0263] 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.

[0264] In some embodiments, the composition comprises a plurality of microbes.

[0265] 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-ethylphenol glucuronide; 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.

[0266] 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.

[0267] 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.

[0268] 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.

[0269] In some embodiments, production of a product can be determined by administering the community of microbes to a gnotobiotic mouse and measuring whether thesubstrate is metabolized and / or the product is produced after a defined period of time by liquid chromatography-mass spectrometry analysis.

[0270] 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.

[0271] 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).

[0272] 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.

[0273] 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.

[0274] 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-linkedglycans; 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.

[0275] 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%; 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.

[0276] 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-acetyl-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.

[0277] 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.

[0278] 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.

[0279] 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.

[0280] 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.

[0281] In some embodiments, the composition achieves substantial engraftment when administered to a gnotobiotic mouse.

[0282] In some embodiments, the community of microbes is stable following a human fecal community microbial challenge.

[0283] In some embodiments, the composition comprises two or more microbial consortiums.

[0284] In some embodiments, the composition is supplemented with a biological active ingredient or agent.

[0285] In some embodiments, biotherapeutic composition comprising the composition of an embodiment of the invention, together with an acceptable diluent or carrier.

[0286] In some embodiments, a pharmaceutical composition comprising the composition of an embodiment of the invention, together with a pharmaceutically acceptable diluent or carrier.

[0287] In some embodiments, a dosage form comprising the composition according to an embodiment of the invention.

[0288] In some embodiments, the dosage form is a unity dosage form.

[0289] 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 NO’S 1 to 286.

[0290] 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 NO’S 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%.

[0291] 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 1 1 ; Table 12; Table 13; Table 14; Table 15; Table 16.

[0292] In some embodiments, the microbe has a less than 97% sequence identity (16S) to the NCBI 16S refSEQ database.

[0293] In some embodiments, a formulation comprising: the composition of an embodiment of the invention, wherein the formulation is formulated as a capsule, tablet, or powder.

[0294] 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.

[0295] 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.

[0296] 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.

[0297] 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.

[0298] 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.

[0299] 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, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, and Vescimonas coprocola.

[0300] In some embodiments, the formulation is generated by co-culturing the core community microbial species and the keystone microbial species in a single bioreactor.

[0301] In some embodiments, the formulation is configured to metabolize hydrogen sulphide in the gastrointestinal tract of a subject post administration of the formulation.

[0302] In some embodiments, the formulation is formulated for oral delivery.

[0303] In some embodiments, the formulation is lyophilized.

[0304] In some embodiments, the pharmaceutically acceptable excipient comprises maltodextrin.

[0305] In some embodiments, the formulation further comprises a prebiotic.

[0306] In some embodiments, the formulation is encapsulated within an enteric coating.

[0307] In some embodiments, the plurality of core community microbial species comprises all of the minimum core species in Table 14.

[0308] In some embodiments, the plurality of keystone microbial species comprises all of the keystone species in Table 13.

[0309] In some embodiments, a formulation comprising a plurality of microbial species comprising all of the species of Tables 13 and 14.

[0310] The use of the formulation of an embodiment of the invention for the treatment of dysbiosis.

[0311] The use of the formulation of an embodiment of the invention for the treatment of ulcerative colitis.

[0312] The use of the formulation of an embodiment of the invention for the treatment of Crohn’s Disease.

[0313] The use of the formulation of an embodiment of the invention 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.

[0314] In some embodiments, in combination with a therapy specific to the one or more diseases or disorders.

[0315] 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.

[0316] 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.

[0317] In some embodiments, the plurality of core community microbial species comprise minimum core species selected from the strains identified in Table 14; and

[0318] In some embodiments, the plurality of keystone microbial species comprise keystone species selected from the strains identified in Table 13.

[0319] In some embodiments, a formulation for oral administration comprising: 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, Enterocloster, Faecalibacterium, Parabacteroides, 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.

[0320] In some embodiments, a formulation comprising: a plurality of core community microbial species, wherein said core community microbial species comprise members of atleast 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.

[0321] In some embodiments, a formulation comprising: 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.

[0322] 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 species: Alistipes dispar, Bacteroides salyersiae, Bifidobacterium bifidum, Christensenella minuta, Coprococcus catus, Coprococcus sp000154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis, Parabacteroides goldsteinii, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, Vescimonas coprocola.

[0323] In some embodiments, a formulation comprising a plurality of core community microbial species and a plurality of keystone microbial species comprising 80-100% of the species identified on Tables 9; Table 10 or Table 11.

[0324] In some embodiments, a formulation comprising: 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.

[0325] The formulation of an embodiment of the invention, where the formulation does not comprise any bacteria from the phylum Pseudomonadota or Campylobacterota.

[0326] 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.

[0327] 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.

[0328] 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.

[0329] In some embodiments, a method of 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 invention.

[0330] In some embodiments, a method of 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 invention.

[0331] In some embodiments, wherein 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.

[0332] In some embodiments, a method of 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 invention.

[0333] In some embodiments, the composition is produced from culturing the consortium in a bioreactor.

[0334] In some embodiments, the composition is healthy donor derived.

[0335] In some embodiments, the dysbiosis is an imbalance or perturbation of the microbiota.

[0336] In some embodiments, the dysbiosis is a disruption in the normal balance of microbial communities in the body, particularly the gut.

[0337] In some embodiments, the dysbiosis is an imbalance caused by a variety of reasons, such as antibiotics, certain diets, stress, or diseases.

[0338] 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.

[0339] 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.

[0340] In some embodiments, said method demonstrates a property selected from the group consisting of:

[0341] In some embodiments, certain strains in the co-culture and / or formulation for administration to a subject are selected based on these phenotypes.

[0342] a. emergent metabolic functions;

[0343] 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;

[0344] 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;

[0345] 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;

[0346] 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));

[0347] f. synergistic metabolic functions relating to: short-chain fatty acids (SCFAs); sulfide homeostasis; energy harvest; tryptophan metabolism; bile acid metabolism; vitamin production; drug metabolism;

[0348] g. reduces sulfide and nitric oxide load on epithelial cells which leads to a metabolic lesion via inhibition of cellular respiration;

[0349] h. reduces relative abundance and or metabolic activity of sulfidogenic microbiota in vitro;

[0350] 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;

[0351] j. reduces sulfide levels in vitro via metabolic substrate competition;

[0352] k. reduces sulfide levels in vitro by consuming hydrogen;

[0353] I. reduces relative abundance and or metabolic activity of sulfidogenic microbiota;

[0354] m. reduce 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;

[0355] 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;

[0356] o. induces colonocyte apoptosis in lesions to break an induced stable inflammatory state driven;

[0357] p. drives down undesired inflammation;

[0358] q. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host protease activity;

[0359] r. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host protease activity;

[0360] s. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial protease activity;

[0361] t. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing microbial protease activity;

[0362] u. reduces sulfide (production in the colon by modulating host protease activity;

[0363] v. reduces sulfide production in the colon by reducing host protease activity;

[0364] w. reduces sulfide production in the colon by modulating microbial protease activity;

[0365] x. reduces sulfide production in the colon by reducing microbial protease activity;

[0366] y. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating host antiprotease (protease inhibitor) activity;

[0367] z. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by reducing host antiprotease (protease inhibitor) activity;

[0368] aa. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine) into the colon by modulating microbial antiprotease (protease inhibitor) activity;

[0369] ab. reduces sulfur amino acid release (methionine, cysteine, homocysteine, taurine)

[0370] ac. into the colon by reducing microbial antiprotease (protease inhibitor) activity;

[0371] ad. reduces sulfide production in the colon by modulating host antiprotease (protease inhibitor) activity;

[0372] ae. reduces sulfide production in the colon by reducing host antiprotease (protease inhibitor) activity;

[0373] af. reduces sulfide production in the colon by modulating microbial antiprotease (protease inhibitor) activity;

[0374] ag. reduces sulfide production in the colon by reducing microbial antiprotease (protease inhibitor) activity;

[0375] 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;

[0376] ai. decreases inflammation in the subject;

[0377] aj. decreases inflammation in the subject when measured by a parameter selected from the group consisting of: TNFa signaling via NF-KB; I FNO signaling; IFNy signaling; IL6 JAK STAT3 signaling; activation of pro-apoptotic pathways; initiation of unfolded protein response;

[0378] 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 ;

[0379] al. treats and / or prevents dysbiosis;

[0380] am. treats or prevents a medical disorder or disease associated with dysbiosis;

[0381] an. treats or prevents a medical disorder or disease associated with mycobiome dysbiosis;

[0382] ao. treats and / or prevents a gastrointestinal disorder;

[0383] 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;

[0384] aq. treats and / or prevents gastrointestinal tract mucosal inflammation;

[0385] 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;

[0386] as. treats and / or prevents inflammatory bowel disease;

[0387] at. treats and / or prevents ulcerative colitis; Crohn's disease; gastroenteritis; colitis; checkpoint inhibitor colitis; and pouchitis;

[0388] 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;

[0389] 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, Alterileibacterium, Amedibacillus, Amedibacterium, Aminipila, Anaerobutyricum, Anaerococcus, Anaerocolumna, Anaerofustis, Anaerostipes, Anaerotignum, Anaerotruncus, Bacillus, Bacteroides, Bamesiella, 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, Ligilactobacillus, 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 and Vescimonas or any combination, subgroup or multitude thereof;

[0390] 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, Pre vote I la, 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

[0391] 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.

[0392] In some embodiments, the composition is administered orally, colonically or rectally.

[0393] 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; twicemonthly; 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.

[0394] In some embodiments, 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, Bamesiella, 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, Pre vote Ila, 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, said method comprising the step of administering to a patient in need thereof, a composition of an embodiment of the invention.

[0395] In some embodiments, 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, Ugilactobacillus, Mediterraneibacter, Minicystis, Oscillibacter, Parabacteroides, Pluralibacter, Prevotella, Prosthecochloris, Pseudomonas, Rhodococcus, Salmonella, Schaalia, Serratia, Shewanella, Staphylococcus, Streptomyces, Sutterella, Veillonella, and any combination or multitudethereof, said method comprising the step of administering to a patient in need thereof, a composition of an embodiment of the invention.

[0396] In some embodiments, a method of preparing the composition of an embodiment of the invention, the method comprising culturing the microbial consortium of an embodiment of the invention.

[0397] 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 1 L 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.

[0398] In some embodiments, the bioreactor is adapted for continuous fermentation.

[0399] In some embodiments, a method of preparing the biotherapeutic composition of an embodiment of the invention, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

[0400] In some embodiments, a method of preparing the pharmaceutical composition of an embodiment of the invention, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

[0401] In some embodiments, a method of preparing the dosage form of an embodiment of the invention, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

[0402] 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.

[0403] 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.

[0404] 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.

[0405] 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 rarefaction curve where the model’s asymptote intersects with the benchmark functional potential or property.

[0406] In some embodiments, method comprises the following steps:

[0407] 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.

[0408] Step 2 - Whole genome sequencing: Subjecting the selected microbial isolates to whole genome sequencing to obtain sequence data.

[0409] 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.

[0410] 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.[0041 1] 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.

[0412] 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.

[0413] 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.

[0414] 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.

[0415] 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.

[0416] 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 offunctional potential or property, ensuring that the consortium is both functionally robust and economically feasible for therapeutic applications.

[0417] In some embodiments, the use of the composition according to an embodiment of the invention 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.

[0418] In some embodiments, a kit comprising the dosage form of an embodiment of the invention together with instructions for its use.

[0419] 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.

[0420] Below we present several embodiments of the invention.

[0421] BY PHYLUM

[0422] Table 1 - By phylum.

[0423] In some embodiments, the formulations 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.

[0424] Table 2 - By Phyum

[0425] In some embodiments, the formulations include one or more microbes selected from one or more of the microbial genera as set forth in Table 2.

[0426] Table 3 - By Phylum. In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial phyla as set forth in Table 3.

[0427] BY FAMILY

[0428] Table 4 - By families. In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial families as set forth in Table 4.

[0429] Table 5 - By Families.

[0430] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial families as set forth in Table 5.

[0431] Table 6 - By Families

[0432] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial families as set forth in Table 6.

[0433] BY GENUS

[0434] Table 7 - By Genera.

[0435] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial genera as set forth in Table 7.

[0436] Table 8 - By Genera.

[0437] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial genera as set forth in Table 8.

[0438] BY SPECIES

[0439] Table 9 - By Species.

[0440] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial species as set forth in Table 9.

[0441] Table 10 - By Species.

[0442] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial species as set forth in Table 10.

[0443] Table 11 - By Species.

[0444] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial species as set forth in Table 11 .

[0445] Table 12 - Species of a further embodiment of the invention.

[0446] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial species as set forth in Table 12.

[0447] In some embodiments, the formulations 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.

[0448] Table 13 - Microbial Keystones.

[0449] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial species as set forth in Table 13.

[0450] Table 14 - Microbial Core Community.In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial species as set forth in Table 14.

[0451] As used herein, the terms “core community microbial strains” or “core community microbial species” refers to a foundational group of microbes that function in synergy 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 synergistic function in the absence of any one strain or any few strains as set forth in Table 14. In some embodiments, a greater synergistic 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 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

[0452] As used herein, the terms “keystone microbial strains” refers to microbes having a synergistic role in survival, integration, and flourishment of other species in the 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.

[0453] In some embodiments, the formulations 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 inTable 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 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 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 numberof 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.

[0454] In some embodiments, the formulations 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 within a 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.

[0455] Table 15 - Microbial Keystones and Core Community currently represented in the 143 isolates comprising BB265.

[0456] In some embodiments, the composition of the invention includes one or more microbes selected from one or more of the microbial species as set forth in Table 15.

[0457] Table 16 - Microbial Keystones and Core Community taxa in a further embodiment.

[0458] Further features of the present invention are more fully described in the following description of several non-limiting embodiments thereof. This description is included solely for the purposes of exemplifying the present invention. It should not be understood as a restriction on the broad summary, disclosure or description of the invention as set out above.Brief Description of the Drawings

[0459] Below is a brief description of each of the figures and drawings.

[0460] 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).

[0461] 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.

[0462] Figure 3 shows the cysteine and methionine metabolic pathways which are directly related to sulfide production or consumption phenotype. These pathways were obtained from https: / / www.qenome.jp / pathwav / map00270.

[0463] Figure 4 shows the BB265 drug discovery process detailing lead selection and validation prior to consortium validation in a phase 1 study.

[0464] 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 asterix (*) preceding the Isolate ID.

[0465] Figure 6 shows the V3-V4 hypervariable region of the 16S rRNA gene sequences of the 143 isolates comprising the consortium (SEQ ID NOs 1 to 143). 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.

[0466] Figure 7 shows the full-length 16S rRNA gene sequences of the 143 isolates comprising the consortium (SEQ ID NOs 144 to 286). 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 specieslevel discrimination between 16 rRNA gene sequences. The sequences presented are DNA sequences encoding the ribosomal RNA.

[0467] Figure 8 (Figure 8A and 8B) shows the average quantity of sulfide (H2S, S2-, HS ) consumed by microbial isolates identified to have a statistically significant sulfide consumer phenotype relative to the negative control (medium only). Isolates were assayed in triplicate. Significance was determined by unpaired t-tests with Welch’s correction

[0468] Figure 9 shows the taxonomic IDs and lineages for the 143 isolates comprising the consortium. A ‘WGS’ sequence type infers that taxonomy was derived using WholeGenome Sequences. Taxonomy was determined by comparison to the Genome Taxonomy Database (release 220).

[0469] Figure 10 shows the clade tree for the cladistic groups comprising the 143 isolate consortium.

[0470] Figure 11 shows a pie chart displaying the abundance of annotated genes among metabolic pathway categories identified in the 143 isolate BB265 consortium.

[0471] Figure 12 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 22) 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.

[0472] Figure 13 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.

[0473] Figure 14 shows the colony forming units (CFU) determined over time when the 143 isolate BB265 consortium was co-cultured in bioreactors at three difference 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.

[0474] Figure 15 (Figure 15A and 15B) shows the relative abundances of the 143 isolates comprising BB265 after co-culture in triplicate at 1 L scale.

[0475] Figure 16 (Figure 16A and 16B) shows the relative abundances of the 143 isolates comprising BB265 after co-culture, comparing 1 L, 4 L and 20 L bioreactor scales.

[0476] Figure 17 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 using polynomial regression, represented by a blue trend line on the plot. A golden horizontal linewas drawn at 1677 COGs, representing the estimated number of COGs expected to be shared among FMT donor samples.

[0477] Figure 18 shows a schematic of the experimental design used to assess successful engraftment of the BB265 co-culture in a germ-free murine model.

[0478] Figure 19 shows the CFU determined from the feces of mice 2-weeks post receiving a second dose of the BB265 co-culture.

[0479] Figure 20 (Figure 20A and 20B) shows 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.

[0480] Figure 21 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.

[0481] Figure 22 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).

[0482] Figure 23 (Figure 23A and 23B) shows 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 Invention

[0483] 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 invention are discussed, followed by specific examples demonstrating the properties of various embodiments of the invention and how they can be employed. Headings and titles are for organizational purposes and should not be used to limit the disclosure or claims.

[0484] 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.

[0485] 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.

[0486] 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 invention.

[0487] The present invention 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 invention as described herein.1. DEFINITIONS

[0488] 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.

[0489] 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%.

[0490] “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 the patient; 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 optimaltherapeutic 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.

[0491] 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.

[0492] As used herein, the term "microbial consortium" component can refer to a plurality of microbes.

[0493] As used herein, a “carrier” can be any solvents, diluents, excipients or other vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying 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.).

[0494] As used herein, the term "pharmaceutically acceptable carrier" component can refer to a component that is not biologically or otherwise undesirable, i.e., the component maybe incorporated into a composition of the invention 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.

[0495] 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. The subject is for example human.

[0496] 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 invention are at least useful for conditions of the terminal ileum, caecum or rectum.

[0497] 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. 10

[0498] 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.

[0499] 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 strain. 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 knowledge regarding 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 30 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.

[0500] 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.

[0501] 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.

[0502] 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.

[0503] 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.

[0504] 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.

[0505] 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, the sample 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 leastsome 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.

[0506] The unit “cfu” refers to "colony forming unit", which is the number of bacterial cells as revealed by microbiological counts on agar plates.

[0507] 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 (SO42-).

[0508] Other definitions for selected terms used herein may be found within the detailed description of the invention 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 invention belongs.

[0509] 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.

[0510] 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.[0051 1] 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%.

[0512] Embodiments of the invention 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 invention. 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.

[0513] 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.

[0514] 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.

[0515] 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” agent can 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.”

[0516] 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.

[0517] 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.

[0518] While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the scope and spirit being indicated by, for example, the following claims.

[0519] For the methods disclosed herein, the functions performed in the processes and methods may be implemented in differing order. The disclosure of methods or uses may also include instructing the method or use (for example, in instructions for use).

[0520] Features of the embodiments of the invention will now be discussed with reference to the following non-limiting description and examples.2. EMBODIMENTSDysbiosis

[0521] The loss of gut microbial ecology, often referred to as gut dysbiosis, is a growing concern in modern medicine. Factors such as the overuse of antibiotics, Western-style diets high in processed foods and sugars, chronic stress, and reduced exposure to environmental microbes have been implicated in disrupting the delicate balance of the gut microbiome. Losing gut microbes results in a loss of the important health-giving functions that they perform, and a loss of these functions leads to disease. When this balance is disturbed, it can lead to a cascade of health issues ranging from digestive disorders like irritable bowel syndrome to systemic problems such as obesity, type 2 diabetes, and even mood disorders. As we continueto understand the profound impact of the gut microbiome on our health, there is an increasing emphasis on strategies to maintain or restore its ecological balance.

[0522] “Dysbiosis” refers to an imbalance or perturbation of the microbiota and / or microbiome. The term is most often used to describe a disruption in the normal balance of microbial communities in the body, particularly the gut. This imbalance can be due to a variety of reasons, such as antibiotics, certain diets, stress, or diseases.

[0523] In a healthy state, the body's internal microbial communities, including bacteria, fungi, and viruses, are balanced and live in symbiosis, contributing to many physiological processes. Dysbiosis, however, can lead to a number of health issues including inflammatory bowel diseases, allergy, irritable bowel syndrome, obesity and mental illness, and can also affect the efficacy of cancer therapies.

[0524] Network effects within the human gut microbiome play a pivotal role in determining its structure, function, and impact on host health. These effects refer to the intricate web of interactions between different microbial taxa, where the presence or activity of one taxa can influence, and in turn be influenced by, others. Such relationships can be synergistic, where two microbes together exert effects greater than the sum of their individual contributions, or competitive, where they vie for the same resources. For instance, certain bacteria produce compounds that either inhibit harmful microbes or promote the growth of beneficial ones. Additionally, some microbes can modify the gut environment to make it conducive for other species to thrive. This interconnectedness means that a perturbation affecting some microbes can have cascading effects throughout the microbial community. Recognizing these network effects is crucial when considering interventions, as introducing or removing one species might have unforeseen consequences on the broader ecosystem, influencing not just microbial composition but also metabolic outputs and overall gut health. The holistic understanding of these network effects is essential for predicting how changes in the microbiome might impact human health.Emergent functions of the gut microbiome.

[0525] The gut microbiome's role in human health goes beyond digestion, with increasing evidence pointing to its emergent metabolic functions. Many of these functions require the linkage of the huge number of components of the gut microbial ecosystem.

[0526] Short-Chain Fatty Acids (SCFAs): Some of the most studied metabolic products of the gut microbiota are SCFAs, including butyrate, acetate, and propionate. These compounds are produced when bacteria ferment dietary fibers in the colon. They serve as an energy source for colon cells, help in maintaining the gut barrier function, and play roles in regulating immune responses and inflammation.

[0527] Hydrogen sulfide homeostasis: A healthy gut microbiome balances production and consumption of hydrogen sulfide. Excess production can occur with dysbiosis, leading to diseases such as inflammatory bowel disease.

[0528] Energy Harvest: An altered microbiome composition can affect the efficiency of energy extraction from food, which can contribute to obesity and metabolic syndrome. Dysbiosis, or imbalance in the microbiome, has also been linked to other aspects of metabolic syndrome, such as increased inflammation, insulin resistance, and fatty liver disease.

[0529] Tryptophan Metabolism: Gut bacteria can influence the metabolism of tryptophan, an essential amino acid, into various bioactive molecules, some of which have roles in brain function and gut barrier maintenance.

[0530] Bile Acid Metabolism: Bile acids aid in fat digestion. After release into the intestine, gut bacteria can convert primary bile acids into secondary bile acids. These bile acid transformations by the microbiome can influence lipid metabolism, glucose regulation, and energy expenditure.

[0531] Vitamin Production: Certain gut bacteria are known to synthesize vitamins like vitamin K and several B vitamins, which are essential for various bodily functions.

[0532] Drug Metabolism: The gut microbiome can influence the efficacy and toxicity of some medications by modulating pharmacokinetic and pharmacodynamic properties. This has implications for personalized medicine and drug design.

[0533] Link to Cardiovascular Disease: Some gut bacteria can metabolize dietary components like choline and carnitine into trimethylamine (TMA). The liver then converts TMA to trimethylamine N-oxide (TMAO), which has been linked to atherosclerosis and an increased risk of cardiovascular diseases, including, for example, dyslipidaemia, atherosclerotic heart disease, or hypertension.

[0534] As our understanding of the gut microbiome expands, it's evident that it acts as a metabolic "organ," influencing and interacting with various physiological systems. Further research promises to yield more insights into these intricate relationships and their implications for human health.

[0535] Probiotics or live bacterial therapeutics (LBPs) are preparations of live beneficial bacteria intended to confer health benefits to the host. However, their efficacy and scope have had limitations, especially when compared to fecal microbiota transplantation (FMT). Firstly, probiotics or LBPs have often contained a limited number of bacterial strains, which may not be comprehensive enough to restore a dysbiotic gut microbiome. In contrast, FMT introduces a broad spectrum of microbial taxa from a healthy donor, potentially allowing for a more holistic restoration of the recipient's gut ecosystem. Secondly, the survival and persistence of probiotic strains in the gut environment is limited. There is evidence that many probiotic strains do not colonize the gut long-term and are quickly expelled. FMT, on the other hand, delivers acomplete, naturally-occurring microbial community which might have a better chance of successful engraftment. Additionally, while probiotics are often considered safe, there is limited evidence on their efficacy, whereas human donor derived FMT has shown high efficacy, particularly in treating recurrent Clostridium difficile infections and ulcerative colitis. The superior efficacy of FMT in these settings is thought to relate to its breadth of function and composition of organisms evolutionarily adapted to the human gut.

[0536] While FMT has emerged as a promising therapeutic approach for various gastrointestinal disorders, especially recurrent Clostridium difficile infection, it has a number of limitations. A major concern is scalability; sourcing, screening, and preparing donor material for FMT is labor-intensive and lacks the ease of mass-producing specific bacterial strains. This makes widespread application of FMT particularly challenging. Consistency is another issue. Given that FMT material is derived from individual donors, there can be significant variability in microbial composition between batches, leading to unpredictable therapeutic outcomes. Live bacterial therapeutics, being cultured in controlled environments, offer more consistent and reproducible formulations. Moreover, the specificity of the mechanism of action is clearer with live bacterial therapeutics, as they can be designed to target specific pathways or functions. With FMT, the broad and diverse range of microbes introduced means that the exact mechanisms driving therapeutic effects can be difficult to define, making it challenging to tailor treatments for specific conditions. Live bacterial therapeutics allow for more precision, scalability, and consistency in microbial interventions.

[0537] The field of microbial therapeutics requires a platform solution for manufacturing diverse gut microbial therapies as a single drug substance. By selectively growing multiple beneficial strains together, the inventors have harnessed the collective benefits of a diverse microbial community, much like FMT, but with the precision, consistency, and scalability inherent to modern pharmaceutical practices. This method combines the broad functional benefits of a diverse microbial ecosystem with the specificity of targeted bacterial strains, effectively bridging the gap between FMT's holistic approach and the precise intent of traditional drugs. Moreover, producing these co-cultures in controlled environments ensures a consistent microbial composition across batches, eliminating the variability seen in donordependent FMT. By integrating this innovative approach into contemporary pharmaceutical manufacturing, there is potential to realize the full promise of FMT — offering treatments that are both broad-spectrum and condition-specific, all while adhering to stringent industry standards for consistency and scalability.Compositions and Formulations

[0538] The present invention provides a composition for preventing or treating a medical disorder or pathology in a subject in need thereof, said composition comprising at least onestrain of bacteria, archaea or fungi. In some embodiments, the compositions are prepared in formulations for oral, colonic, or rectal delivery.

[0539] In a further embodiment, the composition is selected from the group consisting of: a therapeutic composition; a pharmaceutical composition; a cosmetic composition; and a veterinary composition.

[0540] In several embodiments, compositions are combined with a pharmaceutically acceptable carrier or diluent to produce a pharmaceutical composition (which may be for human or animal use). Suitable carriers and diluents include isotonic saline solutions, for example phosphate-buffered saline. As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent that is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. See, e.g., Remington's Pharmaceutical Sciences, 19th Ed. (1995, Mack Publishing Co., Easton, Pa.) and Remington's The Science and Practice of Pharmacy, 23rdEdition. (2020, Mack Publishing Co., Easton, Pa.) which are herein incorporated by reference.

[0541] A pharmaceutically acceptable carrier can be liquid (e.g., saline), gel or solid form of diluents, adjuvant, excipients or an acid resistant encapsulated ingredient. Suitable diluents and excipients include pharmaceutical grades of physiological saline, dextrose, glycerol, mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, and the like, and combinations thereof. In another aspect, a therapeutic composition may contain auxiliary substances such as wetting or emulsifying agents, stabilizing or pH buffering agents. In an aspect, a therapeutic composition contains about 1%- 5%, 5%-10%, 10%-15%, 15-20%, 20%-25%, 5 25-30%, 30-35%, 40-45%, 50%-55%, 1%- 95%, 2%-95%, 5%-95%, 10%-95%, 15%-95%, 20%-95%, 25%-95%, 30%-95%, 35%-95%, 40%-95%, 45%-95%, 50%-95%, 55%-95%, 60%-95%, 65%-95%, 70%-95%, 45%-95%, 80%- 95%, or 85%-95% of active ingredient, or an amount within a range defined by any two of the aforementioned values. In an aspect, a therapeutic composition contains about 2%-70%, 5%- 60%, 10%-50%, 15%-40%, 20%-30%, 25%-60%, 30%-60%, or 35%-60% of active ingredient, or an amount within a range 10 defined by any two of the aforementioned values.

[0542] The composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. Suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodiumsulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCI, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin), fillers; monosaccharides, disaccharides; and other carbohydrates (such as glucose, mannose, or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate 80, triton, tromethamine, lecithin, cholesterol, tyloxapol); stability enhancing agents (sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, for example sodium or potassium chloride), delivery vehicles, diluents, excipients and / or pharmaceutical adjuvants.

[0543] The optimal composition will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format, and desired dosage. Such compositions may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the biotherapeutic actives of the invention. The form of the pharmaceutical composition depends on the intended mode of administration and therapeutic application.

[0544] The primary vehicle or carrier in a composition is aqueous in nature. For example, a suitable vehicle or carrier may be water for injection, physiological saline solution, possibly supplemented with other materials. Neutral buffered saline or saline mixed with serum albumin are further example vehicles. Other example pharmaceutical compositions comprise T ris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, which may further include sorbitol or a suitable substitute therefore. In one embodiment of the present invention, pharmaceutical compositions may be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents in the form of an aqueous solution.

[0545] The formulation components are present in concentrations that are acceptable to the site of administration. For example, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 to about 8.

[0546] Additional compositions will be evident to those skilled in the art, including formulations of the invention in sustained- or controlled-delivery formulations. Techniques forformulating a variety of other sustained- or controlled-delivery means, such as liposome carriers, bio-erodible microparticles or porous beads and depot injections, are also known to those skilled in the art. Additional examples of sustained-sustained-release preparations include semipermeable polymer matrices in the form of shaped articles, for example, films, or microcapsules. Sustained release matrices may include polyesters, hydrogels, polylactides, copolymers of L-glutamic acid and gamma ethyl-L-glutamate, ethylene vinyl acetate or poly- D(-)-3-hydroxybutyric acid. Sustained-release compositions may also include liposomes, which can be prepared by any of several methods known in the art.

[0547] The composition to be used for in vivo administration can be filtered to remove undesirable components. This may be accomplished by filtration through filtration membranes. In addition, the compositions generally are placed into a sealed container to reduce exposure to oxygen. Once the pharmaceutical composition has been formulated, it may be stored in sealed containers.

[0548] The term "% sequence identity ", as used here, may for example be calculated as follows. A sequence designated the ‘query’ sequence is compared to a sequence designated the ‘subject’, or to a database of subject sequences, using the NCBI-BLAST (Basic Local Alignment Search Tool) toolkit; a speed optimized sequence comparison algorithm that searches for optimal local alignments. The ‘blastn’ command is used at the Unix command line to call for comparisons among DNA sequences, represented as text in the ’FASTA’ format. The program returns a number of statistical metric by which to evaluate the quality of a sequence alignment, of which we rely primarily on the length of the alignment (number of base-pairs) and the ‘pident’; this is the percentage of bases in the alignment that are identical among sequences, that we refer to as “% sequence identity”. The BLAST program is one of the most widely used programs in bioinformatics and is regularly maintained / updated by the NCBI; we used version v2.13.0

[0549] The bacterial strains for use in several embodiments of the present invention can be cultured using standard microbiology techniques as detailed in, for instance, Handbook of Microbiological Media, Fourth Edition (2010) Ronald Atlas, CRC Press, Maintaining Cultures for Biotechnology and Industry (1996) Jennie C. Hunter-Cevera, Academic Press, as well as how detailed in the Examples using YCFA medium.

[0550] In yet a further embodiment, the composition further comprises water.

[0551] In yet a further embodiment, the composition is a liquid, such as an aqueous solution.

[0552] In yet a further embodiment, further comprises a pharmaceutically acceptable carrier.

[0553] In yet a further embodiment, the composition retains its effective biological activity for a period selected from the group consisting of; greater than 24 hours; greater than 36hours; and greater than 48 hours. In several embodiments the composition is stable for periods selected from the group consisting of: 6 months, 1 year and 2 years. In one example, the composition is stable at temperatures selected from the group consisting of: -80°C, -20°C, - 4°C, 4°C, 18°C and 25°C.

[0554] Pharmaceutical and therapeutic compositions are within the scope of the invention.

[0555] The therapeutic composition of the invention may comprise a pharmaceutically acceptable excipient, carrier, buffer, stabilizer or other materials well known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the isolated bacteria present in the therapeutic composition. The precise nature of the pharmaceutically acceptable excipient or other material will depend on the route of administration, which may be, for example, oral or rectal. Many methods for the preparation of therapeutic compositions are known to those skilled in the art (see e.g. Robinson ed., Sustained and Controlled Release Drug Delivery Systems, Marcel Dekker, Inc., New York, 1978).

[0556] The therapeutic composition of the invention may comprise a prebiotic, a carrier, insoluble fiber, a buffer, an osmotic agent, an anti-foaming agent and / or a preservative.

[0557] The therapeutic composition may be made or provided in chemostat medium. Alternatively, the therapeutic composition may be made or provided in saline, e.g., 0.9% saline. It will be understood that any carrier or solution which does not impair viability of the bacteria present in the therapeutic composition and is compatible with administration to an individual may be used.

[0558] The therapeutic composition may be made or provided under reduced atmosphere, i.e., in the absence of oxygen. A synthetic stool preparation may be made or provided under N2, CO2, H2, or a mixture thereof, optionally with controlled levels of partial pressure of N2:CO2:H2.

[0559] Any pharmaceutical composition (and / or additional therapeutic agents) described herein can take 5 the form of tablets, pills, pellets, capsules, capsules containing liquids, capsules containing multiparticulates, powders, solutions, emulsion, drops, suppositories, emulsions, aerosols, sprays, suspensions, delayed-release formulations, sustained-release formulations, controlled-release formulations, or any other form suitable for use.

[0560] The formulations comprising the pharmaceutical compositions described herein can conveniently be presented in unit dosage forms. For example, the dosage forms can be prepared by methods which include 10 the step of bringing the therapeutic agents into association with a carrier, which constitutes one or more accessory ingredients. For example, the formulations are prepared by uniformly and intimately bringing the therapeutic agent into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary,shaping the product into dosage forms of the desired formulation (e.g., wet or dry granulation, powder blends, etc., followed by press tableting).

[0561] The therapeutic composition may be for oral, rectal or colonic administration to the individual. Where the therapeutic composition is for oral administration, the therapeutic composition may be in the form of a capsule, powder or a tablet. Where the therapeutic composition is for rectal administration, the therapeutic composition may be in the form of an enema. The preparation of suitable capsules, tablets, powders and enema is well-known in the art. The capsule or tablet may comprise a coating to protect the capsule or tablet from stomach acid. For example, the capsule or tablet may be enteric-coated, pH dependent, slow- release, and / or gastro-resistant. Such capsules and tablets are used, for example, to minimize dissolution of the capsule or tablet in the stomach but allow dissolution in the small or large intestine.

[0562] Orally dosed formulations, for example, can, in addition to the viable microorganisms comprise, inert compression aids, such as microcrystalline cellulose or oligosaccharide, flow aids, such as a silica gel, or a lubricant of, for example magnesium stearate (vegetable source) or stearic acid (vegetable source).

[0563] A composition disclosed herein can be used as, for example, a food supplement, an edible product or pharmaceutical product. When it is a food supplement, the composition can further comprise a conventional food supplement filler and / or an extender. The composition disclosed herein can also be included in any edible products, such as dairy products, including for example, a milk product, milk, yogurt, curd, ice-cream, dressing, and cheese, beverage products, meat products, and baked goods.

[0564] Suppository formulations, for example, either for rectal use, can in addition to the compositions, comprise, for example, cocoa butter, polyethylene glycol, glycerin or gelatine.

[0565] The composition may comprise a disintegrant, a glidant, and / or a lubricant. Disintegrants aid in the breakup of the compacted mass when placed in a fluid environment. The disintegrant may be any suitable disintegrant such as for example, a disintegrant selected from the group consisting of sodium croscarmellose, crospovidone, gellan gum, hydroxypropyl cellulose, starch, and sodium starch glycolate. The glidant may be any suitable glidant such as for example, a glidant selected from the group consisting of silicon dioxide, colloidal silicon dioxide, and talc. Lubricants are generally always used in the manufacture of dosage forms by direct compression in order to prevent the compacted powder mass from sticking to the equipment during the tableting or encapsulation process. The lubricant may be any suitable lubricant such as for example, a lubricant selected from the group consisting of calcium stearate, magnesium stearate, stearic acid, sodium stearyl fumerate, and vegetable based fatty acids. In the composition and method of several embodiments present invention, the carrier, may be present in the composition in a range of approximately 30% w / w toapproximately 98% w / w. For example, the carrier may be present in the composition in a range of: 30%; 35%; 40%; 45%; 50%; 55%; 60%; 65%; 70%; 75%; 80%; 85%; 90%; 95%; 96%; 97%; 98%; 99%. This weight percentage is a cumulative weight percentage taking into consideration all ingredients present in the carrier.

[0566] Coatings can be used to control the solubility of the composition. Examples of coatings include carrageenan, cellulose acetate phthalate, ethylcelulose, gellan gum, maltodextrin, methacrylates, methylcellulose, microcrystalline cellulose, and shellac.

[0567] The composition may comprise one or more preservatives. Example preservatives include antioxidants, chelating agents, antifungal preservatives, alcohol preservatives, acidic preservatives, and other preservatives.

[0568] Example antioxidants include alpha tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and sodium sulfite.

[0569] Example chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts and hydrates thereof (e.g., sodium edetate, disodium edetate, trisodium edetate, calcium disodium edetate, dipotassium edetate, and the like), citric acid and salts and hydrates thereof (e.g., citric acid monohydrate), fumaric acid and salts and hydrates thereof, malic acid and salts and hydrates thereof, phosphoric acid and salts and hydrates thereof, and tartaric acid and salts and hydrates thereof. Suitable antimicrobial preservatives include benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and thimerosal.

[0570] Example antifungal preservatives include butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid. Suitable alcohol preservatives include ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and phenylethyl alcohol.

[0571] Example acidic preservatives include vitamin A, vitamin C, vitamin E, betacarotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid.

[0572] Other preservatives include tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated hydroxyanisol (BHA), butylated hydroxytoluened (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabi sulfite, potassium sulfite, potassium metabi sulfite, Glydant Plus, Phenonip, methylparaben, Germall 1 15, Germaben II, NeoIone, Kathon, and EuxyL

[0573] The therapeutic composition may be lyophilized. The lyophilized therapeutic composition may comprise one or more stabilizers, cryoprotectants and / or excipients. The lyophilized therapeutic composition may be reconstituted using a suitable diluent prior to administration to the individual. Example stabilisers, cryoprotectants, and / or excipients include trehalose, inulin, maltodextrin, sucrose and other stabilisers, cryoprotectants, and / or excipients either 20 alone or in combination. In some embodiments, the composition is formulated as a lyophilized powder.

[0574] A therapeutic composition according to several embodiments of the present invention may be administered alone or in combination with other treatments, concurrently or sequentially or as a combined preparation with another therapeutic agent or agents, for the treatment of dysbiosis, or a disease associated with dysbiosis as described herein. For example, a strain of the invention may be used in combination with an existing therapeutic agent for inflammatory bowel disease, irritable bowel syndrome, a metabolic disease, a neuropsychiatric disorder, an autoimmune disease, an allergic disorder, a cancer, or hepatic encephalopathy.

[0575] For example, where the therapeutic composition is for the treatment of a dysbiosis associated with cancer, the therapeutic composition may optionally be administered in combination with a cancer immunotherapy, such as an immune check-point inhibitor, to the individual. Examples of check-point inhibitors which may be employed in this context include Programmed cell death protein 1 (PD-1 ) inhibitors, Programmed death-ligand 1 (PD-L1 ) inhibitors, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. Manipulation of the gut microbiota in combination with immune check-point inhibitor treatment has been shown to improve efficacy of immune check-point inhibitors in treating cancer. In one embodiment, the cancer in this context is colorectal cancer, renal cell carcinoma, lung cancer or melanoma.

[0576] In another embodiment, the composition of the invention further comprises immunomodulating compounds. In other embodiments, the immunomodulating compound is a cytokine, chemokine, or complement component that enhances expression of immune system accessory or adhesion molecules, their receptors, or combinations thereof. In some embodiments, the immunomodulating compound include interleukins, for example interleukins 1 to 15, interferons alpha, beta or gamma, tumour necrosis factor, granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), chemokines such as neutrophil activating protein (NAP), macrophage chemoattractant and activating factor (MCAF), RANTES, macrophage inflammatory peptides MIP-1 a and MIP-1 b, complement components, or combinations thereof. In other embodiments, the immunomodulating compound stimulates expression, or enhanced expression of 0X40, OX40L (gp34), lymphotactin, CD40, CD40L, B7.1 , B7.2, TRAP, ICAM-1 , 2 or 3, cytokine receptors, or combination thereof.

[0577] In another embodiment, the immunomodulatory compound induces or enhances expression of co-stimulatory molecules that participate in the immune response, which include, in some embodiments, CD40 or its ligand, CD28, CTLA-4 or a B7 molecule. In another embodiment, the immunomodulatory compound induces or enhances expression of a heat stable antigen (HSA), chondroitin sulfate-modified MHC invariant chain (li-CS), or an intracellular adhesion molecule 1 (ICAM-1 ).

[0578] The therapeutic compositions of the invention may be administered to an individual, for example a human individual. Administration may be in a "therapeutically effective amount", this being sufficient to show benefit to the individual. Such benefit may be at least amelioration of at least one symptom. Thus "treatment" of a specified disease refers to amelioration of at least one symptom. The actual amount administered, and rate and timecourse of administration, will depend on the nature and severity of what is being treated, the particular patient being treated, the clinical condition of the individual patient, the cause of the dysbiosis, the site of delivery of the composition, the type of therapeutic composition, the method of administration, the scheduling of administration and other factors known to medical practitioners. Prescription of treatment, e.g. decisions on dosage etc., is within the responsibility of general practitioners and other medical doctors and may depend on the severity of the symptoms and / or progression of a disease being treated. A therapeutically effective amount or suitable dose of a therapeutic composition of the invention can be determined by comparing its in vitro activity and in vivo activity in an animal model. Methods for extrapolation of effective dosages in mice and other test animals to humans are known. The precise dose will depend upon a number of factors, including whether the therapeutic composition is for prevention or for treatment.

[0579] Formulary ingredients can be contacted with the preparation and mixed or prepared until a formulation is obtained. As will be clear to those of skill in the art, formulation conditions will generally be such that viable microorganisms are retained. In particular high temperatures, for example temperatures in excess of 40°C are avoided.

[0580] The amount of viable microorganisms included in a composition can vary and can be adjusted and optimized as will be appreciated by those of skill in the art. Such optimization may, for example, be achieved by preparing a series of different doses of a viable microorganism. The bacterial 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 in several embodiments 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.

[0581] In an embodiment, the strain of the invention can be administered at, for example, a dosage of 0.01 to 100 x 1011cells / body, 0.1 to 10 x 1011cells / body or 0.3 to 5 x 1011cells / body. Furthermore, for example, the amount ingested per day as the bacteria can be 0.01 to 100 x 1011cells / 60 kg body weight, 0.1 to 10 x 1011cells / 60 kg body weight or 0.3 to 5 x 1011cells / 60 kg body weight or an amount within a range defined by any two of the aforementioned values.

[0582] The content of at least one strain of bacteria, archaea or fungi contained in the orally ingested composition of several embodiments of the present invention may be determined as appropriate depending on its application form. As a dry microbial body it can be, for example, 5 to 50 w / w %, 1 to 75 w / w %, 0.1 to 100 w / w % or 1 to 100 w / w % or an amount within a range defined by any two of the aforementioned values.

[0583] In an embodiment, the composition is a controlled release composition. As used herein, the term "controlled-release" refers to release or administration of a strain of the invention from a given dosage form in a controlled fashion in order to achieve the desired pharmacokinetic profile in vivo. An aspect of "controlled" delivery is the ability to manipulate the formulation and / or dosage form in order to establish the desired kinetics of release.

[0584] Procedures for preparing tablets, powders, caplets, capsules and other forms of compositions of the invention are known to those of ordinary skill in the art and include without limitation wet granulation, dry granulation, and direct compression (for tablets and caplets).

[0585] Wet and dry granulation is used to manufacture tablets, caplets, or capsules. With granulation techniques, a chilsonation is used to manufacture the powder for the dosage forms. A chilsonator houses grooved, rotating rollers that are pressed tightly against one another by hydraulic pressure. Raw materials are placed into the hopper of the chilsonator and are fed by a system of horizontal and vertical screws into the rollers. As materials pass through the grooves in the rollers, it is compacted under very high pressure and emerges from the chilsonator as dense sheets. The sheets are milled into a fine granular powder using a Fitz mill and then passed through a screen to produce a uniform free flowing granule. The chilsonation process results in a finished powder that is two to four times denser than thestarting material, a feature that permits the ingredients to be fashioned into the desired dosage form.

[0586] With dry granulation, the powder may be incorporated into a gelatin capsule or it may be mixed with gelatin to form a tablet or caplet. With wet granulation, the powder is moistened thus creating large "chunks" of material that are subsequently dried and milled to convert the chunks to particles of a desired size for the manufacturing process. Once the particles of a desired size are obtained, the particles are incorporated into a gelatin capsule or mixed with gelatin to form a tablet or caplet.

[0587] General considerations in formulation and / or manufacture can be found, for example, in Remington's The Science and Practice of Pharmacy, 23rdEdition. (2020, Mack Publishing Co., Easton, Pa.) which is incorporated by reference.Prebiotics

[0588] The compositions and methods of several embodiments of the present invention may further 25 comprise one or more prebiotics.

[0589]

[0228] A prebiotic is a substrate that is selectively used by a host microorganism to produce a health benefit in a subject. Without wishing to be bound by theory, prebiotics are added to nutritionally supplement bacteria in the microbiome and / or in a microbial composition, e.g., to stimulate the growth or activity of one or more strains of beneficial bacteria. Additionally, the prebiotics may be added to prevent “shock” to bacterial 30 strains subsequent to their isolation or purification, freezing, freeze-drying, spray-drying, reconstitution in solution and the like.

[0590] A composition of the invention can comprise a prebiotic. Because prebiotics have a chemical structure that resists digestion through the alimentary tract, they reach the colon as intact molecules where they are able to elicit systemic physiological functions and act as fermentable substrates for colonic microflora. Where a prebiotic is combined with a biotherapeutic, the resulting composition is sometimes referred to as a "synbiotic."

[0591] Examples of prebiotics include amino acids, ammonium nitrate, amylose, barley, barley mulch, biotin, carbonate, cellulose, chitin, choline, dietary fibres, fermentable polysaccharides, fructooligosaccharides, fructose, glucose, glycerol, 5 heteropolysaccharide, histidine, homopolysaccharide, hydroxyapatite, inulin, isomaltulose, lactic acid, lactose, lactulose, maltodextrins, maltose, mannooligosaccharides, tagatose, nitrogen, oligodextrose, oligofructoses, oligofructose-enriched inulin, oligosaccharides, pectin, phosphate salts, phosphorus, polydextroses, polyols, potash, potassium, sodium nitrate, starch, resistant starch, sucrose, sulfur, sun fiber, tagatose, thiamine, trans-galactooligosaccharides, trehalose, vitamins, a water-soluble carbohydrate, white navy bean powder, and / or 10 xylooligosaccharides (XOSs), or any combination thereof.

[0592] Additional examples of suitable prebiotics include, but are not limited to, oligosaccharide such as fructooligosaccharides, P95 Nutraflora®, for example, galactooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, human milk oligosaccharides, inulin oligosaccharides, mannan oligosaccharides, pyrodextrin, levan, maltotriose, pectic oligosaccharides, bimuno-galactooligosaccharides, arabinoxylan, fucoidan and resistant starches. Fructooligosaccharides can be extracted from, for example, chicory, artichokes, asparagus, dandelions, dahlias, endive, garlic, leeks, lettuce, and onions.

[0593] In an embodiment, the prebiotic comprises amino acids such as one or more or all of alanine, aspartic acid, glutamic acid, glycine, leucine, isoleucine, proline, serine, threonine and valine.

[0594] In an embodiment, the prebiotic comprises simple sugars which can be a monosaccharide (such as glucose, galactose or fructose) and / or a disaccharide (such as sucrose maltose or lactose).

[0595] In an embodiment, the prebiotic comprises from about 5% (w / w) to about 50% (w / w), about 7.5% (w / w) to about 30% (w / w) or about 10% (w / w) to about 15% (w / w) of the composition. For example, 5% (w / w); 10% (w / w); 15% (w / w); 20% (w / w); 25% (w / w); 30% (w / w); 35% (w / w); 40% (w / w); 45% (w / w); 50% (w / w); 55% (w / w); 60% (w / w); 65% (w / w); 70% (w / w); 75% (w / w); 80% (w / w); 85% (w / w); 90% (w / w); 95% (w / w); 96% (w / w); 97% (w / w); 98% (w / w); 99% (w / w), or an amount within a range defined by any two of the aforementioned values.

[0596] In embodiments, a prebiotic can be added (e.g., in dry or liquid forms) to a microbial composition of the present invention.

[0597] Alternately, or additionally, a prebiotic can be included (e.g., in dry or liquid forms) in a distinct pharmaceutical composition which lacks a microbial composition of several embodiments of the present invention.

[0598] A prebiotic may be provided to a subject before, contemporaneously with, and / or after a pharmaceutical composition comprising a microbial composition of several embodiments of the present invention is administered, either in a pharmaceutical composition comprising the microbial composition or in a pharmaceutical composition lacking a microbial composition.

[0599] A prebiotic may be provided in a single dose or in multiple doses. When provided as a single 5 composition, the single composition may comprise a single prebiotic or a mixture of prebiotics. When provided in multiple compositions, each composition may comprise a single prebiotic or a mixture of prebiotics.

[0600] In some embodiments, the compositions described herein are formulated together with a prebiotic in a single formulation. In some embodiments, the compositions described herein are formulated for administration separately from the prebiotic 10 in a separatecomposition. In some embodiments, the compositions of the microbial consortium and the prebiotic may be provided as separate compositions that are co-located in a container. In some embodiments, a kit is provided including the formulations, together or separately along with instructions for use.Other Microorganisms

[0601] In order to obtain the desired health benefit to the subject, it may be advantageous to include one or more additional biotherapeutic microorganisms in the composition. Thus, the composition may comprise more than one species / strain of microorganisms in addition to the strain of the invention, such as two, three, four, five or a higher plurality of species / strains of microorganisms. Non-limiting examples of biotherapeutics are suitable strains selected from the genera listed in Tables 7 and 8. Another example of biotherapeutics to add to the composition are strains of the genera selected from the group consisting of: Acetobacterium, Adlercreutzia, Aerococcus, Akkermansia, Alistipes, Allobaculum, Anaerostipes, Blautia, Bacillus, Bacteroides, Bifidobacterium, Carnobacterium, Clostridium, Coprococcus, Eubacterium, Enterococcus, Erysipelatoclostridium, Faecalibacterium, Lactobacillus, Lactococcus, Leuconostoc, Methanobrevibacter, Oenococcus, Oscillospira, Parabacteroides, Pediococcus, Prevotella. Propionibacterium, Roseburia, Ruminococcus, Sporolactobacillus, Sporomusa, Staphylococcus, Streptococcus, Subdoligranulum, Tetragenococcus, Vagococcus and Weisella. It is to be understood that the foregoing list is intended only to be illustrative and not a limiting representation of the biotherapeutics that may be included. In this respect, any additional biotherapeutic species may also be used in the compositions of the present invention.

[0602] In an embodiment, the Lactobacillus sp. is selected from the group consisting of Lactobacillus rhamnosus (such as strain GG (ATCC 53103), CGMCC 1.3724 or SP1 (DSM 21690)), Lactococcus lactis, Lactococcus cremoris, Lactococcus diacetylactis, Lactobacillus paracasei, Lactobacillus reuteri (such as strain ATCC 55730 or DSM 17938), Lactobacillus acidophilus, Lactobacillus murinus, Lactobacillus helveticus, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus salivarius, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus taiwanensis, Lactobacillus animalis, Lactobacillus johnsonii (such as strain NCC533; CNCM 1 -1225) and Lactobacillus gasseri.

[0603] In an embodiment, the Bifidobacterium sp. is selected from the group consisting of Bifidobacterium lactis (such as strain BB-12, BI-04 or CNCM 1 -3446 (Bb12)), Bifidobacterium longum (such as strain NCC3001 , ATCC BAA-999 (BB536)), Bifidobacterium breve (such as strain Bb-03, M-16V or R0070), Bifidobacterium infantis, Bifidobacterium animalis, Bifidobacterium bifid urn and Bifidobacterium adolescentis.

[0604] In an embodiment, the Clostridium sp. includes or Clostridium hylemonae or Clostridium scindens or Flavinofractor plautii.

[0605] Some yeasts are also useful as biotherapeutics and are sometimes included in the compositions. One non-limiting example of a yeast used in biotherapeutics is Saccharomyces boulardii.

[0606] Some archaea are also useful as biotherapeutics and are sometimes included in the compositions. Non-limiting examples of an archaea used in biotherapeutics is Methanobrevibacter spp, including Methanobrevibacter smithii and Methanosphaera sp, including Methanobrevibacter stadtmanae.

[0607] Further embodiments in this aspect of the invention

[0608] In several embodiments, a formulation comprising multiple core community microbial strains as well as multiple keystone microbial strains are provided to, for example, restore gut microbiome ecology. Advantageously in several embodiments, the core community and keystone strains are co-cultured together to provide a synergistic 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.

[0609] 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. The formulations are 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, primary biliary cirrhosis, 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 usedin 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.

[0610] 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.[0061 1] In some embodiments, the microbial consortium includes at least one microbe of the phylum selected from the group consisting of Actinomycetota, Bacillota, Bacteroidota, Campylobacterota, Pseudomonodota, Thermodesulfobiota, and Verrocomicrobiota. In some embodiments, the microbial consortium includes a microbe from any one of these phyla, any combination of two of these phyla, any combination of three of these phyla, any combination of four of these phyla, any combination of five of these phyla, any combination of six of these phyla, or all seven of these phyla.

[0612] In some embodiments, the microbial consortium includes at least one microbe of the phylum selected from the group consisting of Actinomycetota, Bacillota, Bacteroidota, and Verrocomicrobiota. In some embodiments, the microbial consortium includes a bacteria selected from: Actinomycetota; Bacillota; Bacteroidota; Verrocomicrobiota; Actinomycetota and Bacillota; Actinomycetota and Bacteroidota; Actinomycetota and Verrocomicrobiota; Bacillota and Bacteroidota; Bacillota and Verrocomicrobiota; Bacteroidota and Verrocomicrobiota; Actinomycetota, Bacillota, and Bacteroidota; Actinomycetota, Bacillota, and Verrocomicrobiota; Actinomycetota, Bacteroidota, and Verrocomicrobiota; Bacillota, Bacteroidota, and Verrocomicrobiota; or Actinomycetota, Bacillota, Bacteroidota, and Verrocomicrobiota.

[0613] In some embodiments, the formulations include one or more microbes selected from one or more of the following microbial families: Acidaminococcaceae, Akkermansiaceae, Bacillaceae, Bacteroidaceae, Barnisiellaceae, Bifidobacteriaceae, Campylobacteraceae,Carnobacteriaceae, Christensenellaceae, Clostridiaceae, Coprobacillaceae, Coriobacteriaceae, Desulfovibrionaceae, Eggerthellaceae, Enterobacteriaceae, Enterococcaceae, Erysipelotrichaceae, Eubacteriaceae, Eubacteriales Family XIII. Incertae Sedis, Eubacteriales incertae sedis, Lachnospiraceae, Lactobacillaceae, Maliibacteriaceae, Muribaculaceae, Odoribacteraceae, Oscillospiraceae, Peptoniphilaceae, Peptostreptococcaceae, Prevotellaceae, Rikenellaceae, Selenomonadaceae, Streptococcaceae, Sutterellaceae, and Veillonellaceae. In some embodiments, the formulations include one or more microbes selected from any one of the aforementioned families, or from any combination of 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, or 33 of the aforementioned bacterial families, or from all 34 of the aforementioned bacterial families.

[0614] In several embodiments, a formulation 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 co-cultured, 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, the formulation in one embodiment 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, Soli baculum 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 formulation for administration to a subject. In some embodiments, 90, 92, 95% or all of the core community strains and all of the keystonesstrains 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 administration to a subject. In one embodiment, about 5-20% of strains that are in the co-culture are not significantly present in the formulation for administration to a subject.

[0615] In one embodiment, 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.

[0616] 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 Campylobacterotaare completely or significantly excluded or removed from the formulations.

[0617] In some embodiments, the formulation (whether co-cultured or for administration to a subject) does not include bacteria of the species Acidaminococcus intestini , Bacillus bombysepticus, Bacillus cereus, Bacteroides fragilis , Blautia pseudococcoides , Burkholderiales bacterium 1 1 47, Campylobacter coli , Campylobacter jejuni , Clostridium botulinum, Clostridium paraputrificum , Clostridium perfringens , Clostridium perfringens , Clostridium tetani , Desulfovibrio piger , Eggerthella lenta , Enterococcus faecium , Erysipelatoclostridium ramosum , Escherichia coli , Escherichia marmotae , Finegoldia magna , Flavonifractor plautii , Klebsiella pneumoniae , Klebsiella variicola , Lactococcus lactis , Paraclostridium bifermentans , Pluralibacter gergoviae , Porphyromonas asaccharolytica , Ruminococcus gnavus , Salmonella enterica , Staphylococcus aureus ,Streptococcus infantarius , Streptococcus salivarius , Sutterella wadsworthensis, Thomasclavelia spiroformis , Veillonella parvula, and in some embodiments are completely or significantly excluded or removed. In some embodiments, the formulation (whether cocultured or for administration to a subject) does not include bacteria of the species Bacillus bombysepticus, Bacillus cereus, Bacteroides fragilis , Campylobacter coli , Campylobacter jejuni , Clostridium botulinum, Clostridium perfringens , Clostridium perfringens , Clostridium tetani , Klebsiella pneumoniae , Klebsiella variicola , Pluralibacter gergoviae , Salmonella enterica , Staphylococcus aureus, and in some embodiments are completely or significantly excluded or removed. In some embodiments, the formulation (whether co-cultured or for administration to a subject) does not include bacteria from of the species Burkholderiales bacterium 1 1 47 , Clostridium paraputrificum , Enterococcus faecium , Erysipelatoclostridium ramosum , Finegoldia magna , Lactococcus lactis , Paraclostridium bifermentans , Porphyromonas asaccharolytica , Ruminococcus gnavus , Streptococcus infantarius , Streptococcus salivarius , Sutterella wadsworthensis, Thomasclavelia spiroformis, and in some embodiments are completely or significantly excluded or removed. In some embodiments, the formulation (whether co-cultured or for administration to a subject) does not include bacteria from of the species Acidaminococcus intestini , Blautia pseudococcoides , Desulfovibrio piger , Eggerthella lenta , Escherichia coli , Escherichia marmotae , Flavonifractor plautii , Veillonella parvula, and in some embodiments are completely or significantly excluded or removed. In several embodiments, the formulation (whether co- cultured or for administration to a subject) does not include bacteria from of the species.

[0618] 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, synergistic effects are achieved using the formulations described herein and other therapies such as pharmaceuticals.

[0619] 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 of the 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.

[0620] Methods of co-culturing one or more core community microbial strains with one or more keystone microbial strains are also provided. In some embodiments, the method comprises selecting a plurality of core community microbial strains selected from Table 14 and a plurality of keystone microbial strains selected from Table 13, and co-culturing the strains under suitable culture conditions (e.g., in a single bioreactor). In some embodiments, the method comprises or consists essentially of co-culturing (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 co-culture 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 co-culture 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 coculture. Co-culturing occurs in a single bioreactor in several embodiments, and the keystone strains may facilitate the growth, activity, and / or survival of the core community strains. In one embodiment, about 5-20% of strains that are in the co-culture are not significantly present in the formulation for administration to a subject. In one embodiment, the method further comprises excluding certain bacteria or other microorganisms. In several embodiments, the co-culturing method includes the use of a medium, which contains the following components in varying concentrations per liter: (-)-riboflavin ranges broadly from 10 pg to 100 pg, optionally from 20 pg to 75 pg, preferably from 40 pg to 60 pg, and most preferably about 50 pg. 4- aminobenzoic acid ranges broadly from 5 pg to 50 pg, optionally from 10 pg to 30 pg, preferably from 10 pg to 20 pg, and most preferably about 15 pg. Acetic acid ranges broadly from 2 mL to 10 mL, optionally from 3 mL to 6 mL, preferably from 3.5 mL to 5 mL, and most preferably about 4.05 mL. Ammonium sulfate ranges broadly from 0.5 g to 2 g, optionally from 0.75 g to 1.25 g, preferably from 0.8 g to 1 g, and most preferably about 0.9 g. Biotin ranges broadly from 1 pg to 15 pg, optionally from 3 pg to 10 pg, preferably from 4 pg to 6 pg, and most preferably about 5 pg. Calcium chloride ranges broadly from 0.05 g to 0.2 g, optionally from 0.07 g to 0.15 g, preferably from 0.08 g to 0.1 g, and most preferably about 0.09 g. Cyanocobalamin (B12) ranges broadly from 2 pg to 15 pg, optionally from 4 pg to 10 pg, preferably from 4.5 pg to 6 pg, and most preferably about 5 pg. D-(+)-cellobiose, D-(+)- glucose, and D-(+)-maltose each range broadly from 1 g to 5 g, optionally from 1 .5 g to 3.5 g, preferably from 1 .8 g to 2.2 g, and most preferably about 2 g. Ethanol ranges broadly from 1 mL to 5 mL, optionally from 2 mL to 4 mL, preferably from 2.3 mL to 2.7 mL, and most preferably about 2.5 mL. Folic acid ranges broadly from 10 pg to 100 pg, optionally from 20 pg to 50 pg, preferably from 20 pg to 30 pg, and most preferably about 25 pg. Haemin chloride ranges broadly from 5 mg to 30 mg, optionally from 7 mg to 15 mg, preferably from 9 mg to12 mg, and most preferably about 10 mg. Isobutyric acid and isovaleric acid each range broadly from 0.1 mL to 1 mL, optionally from 0.15 mL to 0.5 mL, preferably from 0.2 mL to 0.3 mL, and most preferably about 0.24 mL. L-cysteine ranges broadly from 0.5 g to 2 g, optionally from 0.75 g to 1 .5 g, preferably from 0.9 g to 1 .1 g, and most preferably about 1 g. Magnesium sulfate ranges broadly from 0.05 g to 0.15 g, optionally from 0.07 g to 0.1 g, preferably from 0.08 g to 0.1 g, and most preferably about 0.09 g. Potassium hydroxide ranges broadly from 10 mg to 50 mg, optionally from 20 mg to 40 mg, preferably from 25 mg to 30 mg, and most preferably about 28 mg. Potassium phosphate dibasic and potassium phosphate monobasic each range broadly from 0.2 g to 1 g, optionally from 0.35 g to 0.75 g, preferably from 0.4 g to 0.5 g, and most preferably about 0.45 g. Propionic acid ranges broadly from 0.5 mL to 3 mL, optionally from 1 mL to 2 mL, preferably from 1.3 mL to 1.6 mL, and most preferably about 1.43 mL. Pyridoxine ranges broadly from 25 pg to 100 pg, optionally from 50 pg to 80 pg, preferably from 60 pg to 70 pg, and most preferably about 75 pg. Resazurin ranges broadly from 0.5 mg to 2 mg, optionally from 0.75 mg to 1 .5 mg, preferably from 0.9 mg to 1 .1 mg, and most preferably about 1 mg. Sodium chloride ranges broadly from 0.5 g to 2 g, optionally from 0.75 g to 1 .5 g, preferably from 0.8 g to 1 g, and most preferably about 0.9 g. Sodium hydrogen carbonate (sodium bicarbonate) ranges broadly from 2 g to 8 g, optionally from 3 g to 6 g, preferably from 3.5 g to 4.5 g, and most preferably about 4 g. Thiamine hydrochloride ranges broadly from 10 pg to 100 pg, optionally from 25 pg to 75 pg, preferably from 40 pg to 60 pg, and most preferably about 50 pg. Tryptone ranges broadly from 5 g to 20 g, optionally from 8 g to 15 g, preferably from 9 g to 11 g, and most preferably about 10 g. Valeric acid ranges broadly from 0.1 mL to 1 mL, optionally from 0.15 mL to 0.5 mL, preferably from 0.2 mL to 0.3 mL, and most preferably about 0.24 mL. Yeast extract ranges broadly from 1.5 g to 5 g, optionally from 2 g to 4 g, preferably from 2.3 g to 2.7 g, and most preferably about 2.5 g. The culture is incubated at 37°C in a stirred reactor under anaerobic conditions, with purged gas at a flow rate of 0.5 to 5 normal liters per minute, more preferably from 1 to 4 normal liters per minute, and most preferably from 2 to 3 normal liters per minute. The gas mixture can be selected from 10% H2, 10% CO2, 80% N2; 5% H2, 10% CO2, 85% N2; 5% H2, 5% CO2, 90% N2; or other similar combinations that facilitate the desired anaerobic conditions. The pH pf the medium ranges broadly from 5 to 9, optionally from 6 to 8, preferably from 6.5 to 7.5, and most preferably about 7.Dosage Form

[0621] Dosage forms are within the scope of the invention. In an embodiment, the invention provides a dosage form comprising the composition as described in the first aspect of this invention. For example, the dosage form is stored in a sealed and sterile container. Methods of making

[0622] Some embodiments provided herein relate to methods of culturing the microbial consortium described herein. In some embodiments, the methods include co-culturing 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 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 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 communitymicrobial 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 co-culturing any number of core community microbial strains with any number of keystone microbial strains within a range described herein. In some embodiments, the methods include co-culturing any number of the core community microbial strains as set forth in Table 14 with any number of the keystone microbial strains as set forth in Table 13. In several embodiments, the number and / or type of strains are selected to achieve a formulation for administration to a subject that provides a therapeutic benefit (e.g., are therapeutically effective).

[0623] In some embodiments, the microbial consortium is co-cultured under conditions that synergistically enhance growth and proliferation of the core community microbial strains with the keystone microbial strains.

[0624] Although a single bioreactor is used for co-culturing the core community and keystone strains in several embodiments and has advantages, multiple bioreactors may be used in one embodiment.Method for treating

[0625] Methods for preventing or treating a medical disorder, disease or pathology associated with dysbiosis or a loss of gut microbial function are within the scope of the invention. In an embodiment, the invention provides a method for treating a medical disorder, disease or pathology associated with dysbiosis, wherein said method comprises the administration to a patient in need thereof a therapeutically effective amount of the composition as described in the first aspect of this invention.

[0626] In a further embodiment, the dosage form is administered at an amount to treat, or at least partially treat a medical disorder or disease associated with dysbiosis or a loss of gut microbial function.

[0627] A subject that can be treated with the invention will include humans as well as other mammals and animals.

[0628] The effect of the administered therapeutic composition can be monitored by standard diagnostic procedures.

[0629] Methods of the invention can be used to treat or prevent a dysbiosis of the gastrointestinal tract in a subject. "Dysbiosis" in the context of the present invention refers to a state in which the normal diversity and / or function of the microbiota or microbiome, in particular the human gastrointestinal microbiota, is disrupted. Any disruption from the normal state of the microbiota in a healthy individual can be considered a dysbiosis, even if the dysbiosis does not result in a detectable decrease in health in the individual. In an embodiment, the dysbiosis may be associated with one or more pathological symptoms. For example, "dysbiosis" may refer to a decrease in the microbial diversity of the microbiota. Inaddition, or alternatively, "dysbiosis" may refer to an increase in the abundance of one or more bacteria, e.g. one or more pathogenic bacteria, in the microbiota of an individual relative to the abundance of said bacterium or bacteria in the microbiota of a healthy individual, i.e. an individual without a dysbiosis. The pathogenic bacteria present during dysbiosis are often Proteobacteria and resistant to one or more antibiotics. Examples of Proteobacteria include Escherichia, Salmonella, Campylobacter, Vibrio, Helicobacter, and Yersinia species. In some embodiments, administration of the compositions described herein synergistically improve dysbiosis, for example, by improving or restoring beneficial microbiome organisms, reducing growth of harmful microorganisms, or improving or enhancing overall microbial diversity.

[0630] The dysbiosis may be a dysbiosis associated with an enteric bacterial infection or dominant strain, such as an infection or proliferation within the gastrointestinal tract of a pathogenic bacterium. Many bacteria capable of causing infections of the gastrointestinal tract or dysbiosis in humans are known and include: gram-positive bacteria, and gram-negative bacteria. The pathogenic bacterium is a pathogenic species of the genus Blautia, Clostridium, Escherichia, Enterococcus, Klebsiella, Enterobacter, Hungatella, Proteus, Salmonella, Shigella, Staphylococcus, Vibrio, Aeromonas, Campylobacter, Plesiomonas, Bacillus, Helicobacter, Listeria, Veillonella or Yersinia. Examples of such pathogenic bacteria include Clostridium difficile, Clostridium perfringens, Clostridium botulinum, Escherichia coli, Salmonella typhi, Staphylococcus aureus, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Campylobacter fetus, Campylobacter jejuni, Aeromonas hydrophila, Plesiomonas shigelloides, Bacillus cereus, Helicobacter pylori, Listeria monocytogenes, and Yersinia enterocolitica. For example, the pathogenic bacterium is a pathogenic species of the genus Blautia, Bacteroides, Bifidobacterium, Clostridium, Escherichia, Enterobacter, Enterococcus, Hungatella, Klebsiella, Parabacteroides, Phocaeicola, and Veillonella. For example, the pathogenic bacterium is Clostridium difficile, Enterococcus avium, Enterococcus gilvus or Escherichia coli. Escherichia, Hungatella, Klebsiella, Ligilactobacillus, Mediterraneibacter, Parabacteroides, Prevotella, Veillonella,

[0631] Methods of the invention can be used to reduce or prevent gastrointestinal tract mucosal inflammation in a subject using compositions of the invention.

[0632] In an embodiment, the subject has, or is susceptible to having, an inflammatory bowel disease (IBD), periodontal disease, chronic fatigue syndrome, obesity, diabetes mellitus, cardiovascular disease, acne vulgaris, cancer, bacterial vaginosis, or other disease associated with or resulting from dysbiosis. In some embodiments, the subject has or is susceptible to having IBD, such as Crohn's disease, ulcerative colitis and pouchitis.

[0633] As used herein, the term "inflammatory bowel diseases (IBD)" has its general meaning in the art and refers to a group of inflammatory diseases of the colon and small intestine such as revised in the World Health Organisation Classification K20-K93 (ICD-10)such as Crohn disease (such as granulomatous enteritis; Crohn disease of small intestine; Crohn disease of large intestine; granulomatous and regional Colitis; Crohn disease of colon, large bowel and rectum; Crohn disease of both small and large intestine), Ulcerative colitis (such as Ulcerative (chronic) pancolitis; backwash ileitis; Ulcerative (chronic) proctitis; Ulcerative (chronic) rectosigmoiditis; Inflammatory polyps; Left sided colitis; left hemicolitis) and noninfective gastroenteritis and colitis (Gastroenteritis and colitis due to radiation; Toxic gastroenteritis and colitis; Allergic and dietetic gastroenteritis and colitis; Food hypersensitivity gastroenteritis or colitis; indeterminate colitis; specified noninfective gastroenteritis and colitis such as Collagenous colitis; Eosinophilic gastritis or gastr...

Claims

CLAIMS1 . 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.

2. The formulation of claim 1 , wherein the plurality of core community microbial species comprises at least the following species: Dysosmobacter welbionis, Enterocloster bolteae, Ruthenibacterium lactatif ormans, 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 bifid urn, and Coprococcus catus.

3. The formulation of claim 1 , wherein the plurality of core community microbial species comprises at least the following species: Alistipes dispar, Bacteroides salyersiae, Bifidobacterium bifidum, Christensenella minuta, Coprococcus catus, Coprococcus sp000154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis, Parabacteroides goldsteinii, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, and Vescimonas coprocola.

4. The formulation of claim 1 , wherein the formulation is generated by co-culturing the core community microbial species and the keystone microbial species in a single bioreactor.

5. The formulation of claim 1 , wherein the formulation is configured to metabolize hydrogen sulphide in the gastrointestinal tract of a subject post administration of the formulation.

6. The formulation of claim 1 , wherein the formulation is formulated for oral delivery.

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

8. The formulation of claim 1 , wherein the pharmaceutically acceptable excipient comprises maltodextrin.

9. The formulation of claim 1 , further comprising a prebiotic.

10. The formulation of claim 1 , wherein the formulation is encapsulated within an enteric coating.11 . The formulation of claim 1 , wherein the plurality of core community microbial species comprises all of the species in Table 14.

12. The formulation of claim 1 , wherein the plurality of keystone microbial species comprises all of the species in Table 13.

13. A formulation comprising a plurality of microbial species comprising all of the species of Tables 13 and 14.

14. The use of the formulation of any one of claims 1 -13 for the treatment of dysbiosis.

15. The use of the formulation of any one of claims 1 -13 for the treatment of ulcerative colitis.

16. The use of the formulation of any one of claims 1 -13 for the treatment of Crohn’s Disease.

17. The use of the formulation of any one of claims 1 -13 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, primary biliary sclerosis, irritable bowel syndrome, 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.

18. The use of the formulation of claim 17 in combination with a therapy specific to the one or more diseases or disorders.

19. The formulation according to any one of claims 1 -13, wherein 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.

20. The formulation according to any one of claims 1 -13, wherein 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.21 . The formulation of claim 1 , wherein the plurality of core community microbial species comprise strains selected from the strains identified in Table 14; and wherein the pluralityof keystone microbial species comprise strains selected from the strains identified in Table 13.

22. A formulation for oral administration comprising: 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, Enterocloster, Faecalibacterium, Parabacteroides, 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.

23. A formulation comprising a plurality of core community microbial species and a plurality of keystone microbial species comprising 80-100% of the species identified on Tables 4 and 5.

24. A formulation comprising: 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 polyvinlyalcohol; 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.

25. The formulation of any one of claims 1 -13 or 19-24, where the formulation does not comprise any bacteria from the phylum Pseudomonadota or Campylobacterota.

26. 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.

27. The method of claim 26, wherein 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.

28. The method of claim 26, wherein 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.

29. 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 ormultitude 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.

30. A biotherapeutic composition comprising the composition of claim 29, together with an acceptable diluent or carrier.31 . A pharmaceutical composition comprising the composition of claim 29, together with a pharmaceutically acceptable diluent or carrier.

32. A dosage form comprising the composition of claim 29, wherein the dosage form is a unity dosage form.

33. 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 NO’S 1 to 286.

34. 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 1 1 ; Table 12; Table 13; Table 14; Table 15; Table 16.

35. A method of decreasing inflammation in a subject in need thereof, said method comprising administering to the subject an effective amount of the composition of claim 29.

36. A method of decreasing dysbiosis in a subject in need thereof, said method comprising administering to the subject an effective amount of the composition of claim 29.

37. A method of 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 a composition of claim 29.

38. 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, Cate m bacterium, 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, said method comprising the step of administering to a patient in need thereof, the composition of claim 29.

39. 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, Ugilactobacillus, Mediterraneibacter, Minicystis, Oscillibacter, Parabacteroides, Pluralibacter, Prevotella, Prosthecochloris, Pseudomonas, Rhodococcus, Salmonella, Schaalia, Serratia, Shewanella, Staphylococcus, Streptomyces, Sutterella, Veillonella, and any combination or multitude thereof, said method comprising the step of administering to a patient in need thereof, a composition of claim 29.

40. A method of preparing the composition of claim 29, the method comprising culturing the composition of claim 29.41 . A method of preparing the biotherapeutic composition of any one of claim 30, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

42. A method of preparing the pharmaceutical composition of any one of claim 31 , the method comprising mixing the composition with a pharmaceutically acceptable carrier.

43. A method of preparing the dosage form of claim 32, the method comprising mixing the composition with a pharmaceutically acceptable carrier.

44. 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.

45. 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.

46. Use of the composition of claim 29 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.

47. A kit comprising the dosage form of claim 32 together with instructions for its use.

48. 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.

49. The formulation of claim 1 , wherein the plurality of core community microbial species comprises at least one of the following species: Dysosmobacter welbionis, Enterocloster bolteae, Ruthenibacterium lactatif ormans, 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.

50. The formulation of claim 1 , 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 sp000154245, Dysosmobacter faecalis, Faecalibacterium duncaniae, Gemmiger formicilis, Parabacteroides goldsteinii, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Solibaculum mannosilyticum, and Vesci monas coprocola.

Images