Biomarkers for the treatment of bloodstream infections and gastrointestinal diseases
A bacterial composition targeting altered markers in HSCT patients regulates immune response and prevents pathogen domination, addressing the susceptibility to infections and GvHD in HSCT.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- SERES THERAPEUTICS INC
- Filing Date
- 2025-12-12
- Publication Date
- 2026-06-18
AI Technical Summary
Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with increased susceptibility to bloodstream infections and graft-versus-host disease (GvHD) due to immune suppression, necessitating new approaches to prevent and treat these conditions.
Administering a composition of bacteria that exhibit altered expression of markers such as fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, or combinations thereof, to regulate immune response and prevent pathogen domination in the gastrointestinal tract.
Reduces the risk of bloodstream infections and GvHD by modulating the immune response and maintaining gut microbiota balance, effectively preventing pathogen domination.
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Abstract
Description
BIOMARKERS FOR THE TREATMENT OF BLOODSTREAM INFECTIONS AND GASTROINTESTINAL DISEASES CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the priority benefit of U. S. Provisional Application No.63 / 733,877, filed on December 13, 2024, which is incorporated herein by reference in its entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY
[0002] The content of the electronically submitted Sequence Listing XML (Name:4268_104PC01_Sequencelisting_ST26.xml; Size: 1,056,719 bytes; Date of Creation: December 11, 2025) filed with the application is herein incorporated by reference in its entirety.FIELD OF THE DISCLOSURE
[0003] The present disclosure relates to biomarkers that are useful in the treatment of bloodstream infections and / or gastrointestinal diseases or conditions in a subject, e.g., undergoing hematopoietic stem cell transplantation (HSCT).BACKGROUND OF THE DISCLOSURE
[0004] Allogeneic hematopoietic stem cell transplantation (HSCT) is an important treatment with curative intent for hematological malignancies, such as leukemia and lymphoma. Despite its success, HSCT is not without risks. For instance, chemotherapy is commonly used to condition a patient for transplantation, so that the patient's immune system does not reject the transplantation. However, chemotherapy suppresses the patient's immune system and can thereby, increase the patient's susceptibility to infections (e.g., bloodstream infections). Additionally, many HSCTs involve allogenic donors. Even with the use of conditioning regimens (e.g., chemotherapy and antibiotics), life-threatening inflammation, such as that observed in graft-versus-host disease (GvHD), is a significant issue.
[0005] Accordingly, there remains a need for new and alternative approaches to treating the different diseases and disorders that can occur in HSCT patients, such as infections (e.g., bloodstream infections) and GvHD, as well as other diseases and disorders associated with immune suppression, including subjects having cancer, having an allogeneic or an autologous immune response, undergoing chemotherapy, or undergoing or having undergone transplantation.BRIEF SUMMARY OF THE DISCLOSURE
[0006] Provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; and wherein the reference subject comprises a corresponding subject who did not receive an administration of the composition. In some aspects, the preventing and / or reducing a risk of a bloodstream infection comprises reducing an incidence of the bloodstream infection in the subject.
[0007] Also provided herein is a method of reducing and / or preventing a pathogen domination within the gastrointestinal tract of a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; and wherein the reference subject comprises a corresponding subject who did not receive an administration of the composition.
[0008] Provided herein is a method of reducing and / or preventing a pathogen domination within the gastrointestinal tract of a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; and whereinthe reference subject comprises a corresponding subject who did not receive an administration of the composition.
[0009] Provided herein is a method of regulating an inflammatory response in a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; and wherein the reference subject comprises a corresponding subject who did not receive an administration of the composition. In some apsects, after the administering, the inflammatory response is reduced in the subject.
[0010] For any of the methods provided herein, in some aspects, as compared to the reference subject, the expression of the marker is increased in the subject. In some aspects, after the administering, the expression of the marker is decreased in the subject.
[0011] In some aspects, as compared to the reference subject, the expression of the marker is decreased in the subject. In some aspects, after the administering, the expression of the marker is increased in the subject.
[0012] For any of the methods provided herein, in some aspects, the plurality of bacteria comprises Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphda, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassdibacdlus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium bolteae, Clostridium butyricum, Clostridium disporicum, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium sub terminale, Clostridium symbiosum, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis,Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium maltosivorans, Eubacterium rectale, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, or any combination thereof.
[0013] In some aspects, the plurality of bacteria comprises a 16S rDNA sequence that shares at least 97% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352. In some aspects, the plurality of bacteria comprises a 16S rDNA sequence that shares at least 98% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352. In some aspects, the plurality of bacteria comprises a 16S rDNA sequence that shares at least 99% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352. In some aspects, the plurality of bacteria comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 1 to 352.
[0014] Where a method comprises preventing and / or reducing a risk of a bloodstream infection, in some aspects, the bloodstream infection comprises an infection with an ESKAPE pathogen. In some aspects, the bloodstream infection comprises an opportunistic infection with a commensal bacterial species. In some aspects, the bloodstream infection comprises an infection with an antibiotic resistant bacterial species.
[0015] For any of the methods provided herein, in some aspects, the subject has an immunodeficiency. In some aspects, the subject has a non-bloodstream infection. In some aspects, the subject has a gut dysbiosis or disruption. In some aspects, the dysbiosis comprises a gut dysbiosis or disruption, an oral dysbiosis or disruption, or both.
[0016] For any of the methods provided herein, in some aspects, the subject has received, is receiving, or will receive an allogeneic hematopoietic stem cell transplantation (allo- HSCT).
[0017] For any of the methods provided herein, in some aspects, one or more of the plurality of bacteria are lyophilized. In some aspects, one or more of the plurality of bacteria are in a spore form. In some aspects, one or more of the plurality of bacteria are in a vegetative form.
[0018] In some aspects, the composition is formulated for oral delivery. In some aspects, the composition comprises a capsule. In some aspects, the composition comprises an enteric polymer.
[0019] Where a method comprises administering a bacterial composition to a subject, in some aspects, multiple doses of the composition are administered to the subject.
[0020] Also provided herein is a method of identifying a subject who is likely to favorably respond to a composition comprising a plurality of bacteria, wherein the method comprises determining an expression of a marker in a biological sample obtained from the subject, wherein the subject is identified as likely to favorably respond to the composition if the expression of the marker is altered (decreased or increased) as compared to a reference subject, wherein the reference subject comprises a corresponding subject who does not favorably respond to the composition, and wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof. In some aspects, the method further comprises administering the composition to the subject who has been identified as likely to favorably respond to the composition.
[0021] The present disclosure also provides a method of identifying a subject who is responding to a composition comprising a plurality of bacteria, comprising determining an expression of a marker in a biological sample obtained from the subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; wherein prior to the determining, the subject has received an administration of the composition; wherein the subject is responding to the composition if the expression of the marker is altered (decreased or increased) as compared to a reference subject; and wherein the reference subject is: (a) the subject prior to the administration of the composition, (b) a corresponding subject who did not previouslyreceive an administration of the composition, or (c) both (a) and (b). In some aspects, the method further comprises administering an additional dose of the composition to the subject if the subject is responding to the composition.
[0022] For any of the identifying methods provided herein, in some aspects, the plurality of bacteria comprises Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphda, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassdibacdlus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium bolteae, Clostridium butyricum, Clostridium disporicum, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium subterminale, Clostridium symbiosum, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium maltosivorans, Eubacterium rectale, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, or any combination thereof.
[0023] In some aspects, the plurality of bacteria comprises a 16S rDNA sequence that shares at least 97% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352. In some aspects, the plurality of bacteria comprises a 16S rDNA sequence that shares at least 98% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352. In some aspects, the plurality of bacteria comprises a 16S rDNA sequence that shares at least 99% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352. In some aspects, the plurality of bacteria comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 1 to 352.
[0024] For any of the identifying methods provided herein, in some aspects, the subject has received, is receiving, or will receive an allogeneic hematopoietic stem cell transplantation (allo-HSCT). In some aspects, the subject has a bloodstream infection. In some aspects, the bloodstream infection comprises an infection with an ESKAPE pathogen. In some aspects, the bloodstream infection comprises an opportunistic infection with a commensal bacterial species. In some aspects, the bloodstream infection comprises an infection with an antibiotic resistant bacterial species.
[0025] For any of the identifying methods provided herein, in some aspects, one or more of the plurality of bacteria are lyophilized. In some aspects, one or more of the plurality of bacteria are in a spore form. In some aspects, one or more of the plurality of bacteria are in a vegetative form.
[0026] For any of the identifying methods provided herein, in some aspects, the composition is formulated for oral delivery. In some aspects, the composition comprises a capsule. In some aspects, the composition comprises an enteric polymer.
[0027] For any of the identifying methods provided herein, in some aspects, the plurality of bacteria is formulated as two parts, wherein the part 1 comprises a liquid formulation of bacterial spores and the part 2 comprises a dry powder formulation of vegetative bacteria. In some aspects, the part 1 comprises the following strains: Clostridium innocuum: Clostridium boheae Blautia hominis: [Clostridium] scindens: Anaerotruncus coUhominis Murimonas inleslini: Erysipelatoclostridium rctmosum Faecalicatena Orlica Emergencia limonensis: Clostridium aldenense and Eisenbergiella tayi. In some aspects, the strains are delivered at a target dose strength of 6.9 x 106colony-forming units (CFUs) per dose. In some aspects, the part 2 comprises the following strains: Blautia wexlerae Eubacteriumcallander z; Flavonifractor plautir, Dorea longicatena, and Blautia obeum. In some aspects, the strains are delivered at a target dose strength of 3.1 x 107CFUs per dose.
[0028] The present disclosure also provides a composition comprising a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first plurality of bacteria comprises one or more of the following bacteria: Clostridium innocuum. Clostridium boheae. Blautia hominis. Clostridium scindens. Anaerotruncus colihominis, Murimonas inleslini. Erysipelatoclostridium ramosum. Faecalicatena orlica. Emergencia limonensis. Clostridium aldenense. and Eisenbergiella tayi, and wherein the second plurality of bacteria comprises one or more of the following bacteria: Blautia wexlerae, Eubacterium callander i, Flavonifractor plautii, Dorea longicatena, and Blautia obeum. In some aspects, one or more bacteria of the first plurality of bacteria are in a spore form. In some aspects, each of the bacteria of the first plurality of bacteria is in a spore form. In some aspects, one or more bacteria of the second plurality of bacteria are in a vegetative form. In some aspects, each of the bacteria of the second pluarity of bacteria is in a vegetative form. In some aspects, the first formulation is a liquid formulation. In some aspects, the second formulation is a dry powder formulation. In some aspects, a dose of the first formulation is about 6.9 x 106CFUs of bacteria. In some aspects, a dose of the second formulation is about 3.1 x 107CFUs of bacteria. In some aspects, the first formulation comprises glycerol. In some aspects, the second formulation comprises urea. In some aspects, the second formulation comprises a cryoprotectant. In some aspects, the cryoprotectant comprises a sugar. In some aspects, the sugar comprises sucrose. In some aspects, the second formulation comprises an antioxidant. In some aspects, the antioxidant comprises ascorbic acid, cysteine, or both. In some aspects, the cysteine comprises cysteine hydrochloride monohydrate. In some aspects, the second formulation comprises a protein stabilizer. In some aspects, the protein stabilizer comprises gelatin. In some aspects, the gelatin comprises gelatin hydrolysate. In some aspects, the second formulation comprises a salt. In some aspects, the salt comprises potassium chloride. In some aspects, the second formulation comprises a buffering agent. In some aspects, the buffering agent comprises HEPES. In some aspects, the second formulation comprises a neutralizing agent. In some aspects, the neutralizing agent comprises sodium hydroxide. In some aspects, the second formulation comprises a bulking agent. In some aspects, the bulking agent comprisescellulose. In some aspects, the cellulose comprises microcrystalline cellulose. In some aspects, the second formulation comprises a glidant. In some aspects, the glidant comprises silica. In some aspects, the silica comprises hydrophobic colloidial silica. In some aspects, the second formulation comprises a lubricant. In some aspects, the lubricant comprises sodium stearyl fumarate. In some aspects, the first formulation is in a capsule. In some aspects, the second formulation is in a capsule. In some aspects, the capsule is enterically coated.
[0029] In some aspects, (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequenceidentity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequenceset forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
[0030] In some aspects, (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequenceidentity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequenceset forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
[0031] In some aspects, (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequenceidentity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequenceset forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
[0032] In some aspects, (a) the Clostridium innocuum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO:285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
[0033] The present disclosure also provides a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject any one of the compositions provided herein.
[0034] The present disclosure also provides a method of reducing and / or preventing a pathogen domination within the gastrointestinal tract of a subject in need thereof, comprising administering to the subject any one of the compositions provided herein.
[0035] The present disclosure also provides a method of repairing and / or protecting a gut epithelial barrier in a subject in need thereof, comprising administering to the subject any one of the compositions provided herein.
[0036] The present disclosure also provides a method of regulating an inflammatory response in a subject in need thereof, comprising administering to the subject the composition of any one of the compositions provided herein.BRIEF DESCRIPTION OF THE DRAWINGS / FIGURES
[0037] FIG. 1 provides a schematic of the experimental design of the data described in Examples 1 and 2. As shown, the subjects received two treatment courses. The first treatment course was administered prior to HSCT (" Pre-HSCT") and included: 4 days of oral vancomycin pretreatment to condition the microbiome to support engraftment of bacterial composition followed by 10 days of administration of a bacterial composition. The second treatment course was administered after HSCT and also included: 4 days of oral vancomycin pretreatment to condition the microbiome to support engraftment of bacterial composition followed by 10 days of administration of a bacterial composition. The control group received 4 days of placebo vancomycin followed by 10 days of placebo treatment instead of a bacterial composition.
[0038] FIGs. 2A-2C shows bacterial engraftment after administration of a bacterial composition described herein to allo-HSCT subjects. FIG. 2A shows the number of bacteria within the administered bacterial composition that were detected in fecal samples obtained from the subjects. The presence of the bacteria was assessed at the following time points: (a) baseline, (b) after 1stvancomycin pretreatment (" Post-vanc Tl"), (c) after 1stbacterial composition administration (" Post-treatment Tl"), (d) at HSCT (" HSCT Day 0"), (e) after neutrophil recovery after HSCT (" Post-neutrophil recovery"), (f) after 2ndvancomycin pretreatment (" Post-vanc T2"), (g) after 2ndbacterial composition administration (" Post-treatment T2"), and (g) at day 100 post HSCT (" HSCT Day 100"). The numbers provided immediately above the x-axis represent the number of subjects analyzed for each of the time points. FIG. 2B shows the number of the administeredbacteria that engrafted as measured in fecal samples obtained from subjects that did not develop febrile neutropenia (N, left column) and from subjects that did develop febrile neutropenia after administration (Y, right column). FIG. 2C shows the number of the administered bacteria that engrafted as measured in fecal samples obtained from subjects with Grade 0 / 1 GvHD (left column) and from subjects with Grade 11+ GvHD (right column) after administration.
[0039] FIG. 3 shows the percentage of subjects with pathogen domination after administration of a bacterial composition disclosed herein (see left bar for each of the time points). Results are shown as measured after 1stbacterial composition administration ("1stCourse"), at HSCT (" HSCT Day 0"), and after neutrophil recovery after HSCT (" Post Neutrophil Recovery"). For comparison, percentage of subjects with pathogen domination observed from the historical control cohort of HSCT subjects is also provided (see right bar for each of the time points).
[0040] FIG. 4 shows the prevalence of Enterobacteriaceae (top row) and Enter ococcaceae (bottom row) species in fecal samples obtained from subjects that: (a) received two administrations of a bacterial composition ("bacterial composition"), or (b) received placebo alone ("placebo"), and (c) those from the historical control cohort of HSCT subjects (" Historical Control"). Bacterial species prevalence is shown as "cell equivalents per gram of dry stool". For each of the groups, prevalence of the bacterial species is shown for one or more of the following time points: (a) baseline, (b) after 1stvancomycin pretreatment (" Post-vanc Tl"), (c) after 1stbacterial composition administration (" Post-treatment Tl"), (d) at HSCT (" HSCT Day 0"), (e) after neutrophil recovery after HSCT (" Post-neutrophil recovery"), (f) after 2ndvancomycin pretreatment (" Post-vanc T2"), (g) after 2ndbacterial composition administration (" Post-treatment T2"), and (g) at day 100 post HSCT (" HSCT Day 100").
[0041] FIG. 5 shows differences between the arm with subjects that received an administration of a bacterial composition described here and placebo subjects for following biomarkers: fecal albumin, TNF-a, IL-17, IL-8, CXCL10, and IL-10. Differences in which the p value was < 0.1 are shown, with the p value provided and whether treatment or placebo was a higher concentration is indicated. Results are provided for the following time points: (a) after 1stbacterial composition administration (" Post-treatment Tl"), (b) at HSCT(" HSCT Day 0"), and (c) after neutrophil recovery after HSCT (" Neutrophil recovery"). " BC" refers to Bacterial Composition.
[0042] FIG. 6 shows fecal albumin levels in subjects that either did (Y) or did not (N) have a bloodstream infection (BSI) by Day 30 post HSCT. All subjects are included, both those that were treated with a bacterial composition disclosed herein and those from the placebo group. The fecal albumin level was measured at the following time points: (a) baseline, (b) after 1stvancomycin pretreatment (" Post-vanc Tl"), (c) after 1stbacterial composition administration (" Post-treatment Tl"), (d) at HSCT (" HSCT Day 0"), (e) after neutrophil recovery after HSCT (" Post-neutrophil recovery"), (f) after 2ndvancomycin pretreatment (" Post-vanc T2"), (g) after 2ndbacterial composition administration (" Post-treatment T2"), and (g) at day 100 post HSCT (" HSCT Day 100").
[0043] FIGs. 7A-7D show the levels of the following markers as measured in plasma samples obtained from subjects treated with a bacterial composition disclosed herein (left column for each of the time points) and from the placebo group (right column for each of the time points): IL- 17 (FIG.7 A), IFN-y (FIG.7B), CXCL10 (FIG.7C), and TNF-a (FIG.7D). For each of the markers shown, levels as measured at the following time points are provided: (a) after 1stbacterial composition administration and during HSCT conditioning (" HSCT conditioning"), (b) at HSCT (" HSCT Day 0"), and (c) after neutrophil recovery after HSCT (" Post-neutrophil recovery").
[0044] FIG. 8 provides comparison of the concentration profile of different biomarkers in subjects that were treated with a bacterial composition disclosed herein and subjects from the placebo group. The biomarkers shown are as follows: (a) Reg3 A and CXCL10 (markers for local GI inflammation); (b) ST-2, IFN-y, TNFR1, TNF-a, IL-6, CRP, IL- 17, IL-8, and MCP-1 (markers for inflammation); (c) IL-10, IL-15, IL-2Ra, and IL-7 (markers for immune homeostasis); and (d) elafin, HGF, CK-18, and TIM3 (markers for barrier / tissue integrity). The concentration profile for each biomarker is shown as a ratio of the mean concentration observed in subjects treated with the bacterial composition to the mean concentration observed in subjects from the placebo group. Results are provided for the following time points: (a) after 1stbacterial composition administration (" Post-treatment Tl"), (b) at HSCT (" HSCT Day 0"), (c) after neutrophil recovery after HSCT (" Postneutrophil recovery"), (d) after 2ndbacterial composition administration (" Post-treatment T2"), and (e) at day 100 post HSCT (" HSCT Day 100").
[0045] FIG. 9 provides a table identifying the bacterial species included in bacterial compositions DE1-DE54. "0" indicates that the bacterial species is not included; "1" indicates that the bacterial species is included in the given composition.
[0046] FIGs. 10A-10B are schematics showing the study design of the data provided in Example 3.
[0047] FIG. 11 provides strain detection in a randomized, placebo-controlled Cohort.Timepoint is shown on the x-axis, the number of detected strains comprising the bacterial composition is shown on the y-axis. Boxplots represent the distribution of the total detected strains in participants at each timepoint. Numbers along x-axis represent samples per group, per timepoint. Wilcoxon rank sum p-values: NS = not significant, ** = p<0.01, *** = p<0.001.
[0048] FIGs. 12A-12D show clinical outcomes from hematopoietic cell transplant (HCT) Day 0 through HCT Day 100 for randomized, placebo-controlled Cohort 2 for bacterial composition treated and placebo groups. FIG. 12A shows the incidence of bloodstream infection (BSI). Error bars represent 95% confidence intervals (CI). FIG. 12B shows the time to first BSI. FIG. 12C shows the cumulative utilization of systemic antibacterials or antimycotics for treatment of any AE in successive administration days calculated as the sum of all days a participant received systemic antibacterials and / or antimycotics for treatment on or after HCT Day 0 (counting once per day, regardless of number of antibacterial / antimycotic medications taken in a day) through HCT Day 100. FIG. 12D shows the mean cumulative utilization rate of systemic antibacterials or antimycotics for treatment of any AE, calculated as above, divided by the total number of days a participant was on study from HCT Day 0 to the earliest of end of study, or HCT Day 100.
[0049] FIGs. 13A-13E show microbiome composition and prevalence of pathogen domination. FIGs. 13A-13E show Principal Coordinates Analysis (PCoA) based on Bray- Curtis dissimilarity in Cohort 2 bacterial composition trested and placebo arms (safety population) and a comparator cohort of self-described healthy volunteers profiled using the same WMS methods used in the current study. Each point represents a stool sample, the distance between points summarizes global differences in microbial species composition. All samples were clustered as part of the same PCoA; vertical facets separate points by treatment arm / cohort while points across horizontal facets are all identical going from left to right but each column is colored by different microbiome features. Microbiome featuresmapped onto data points describe (a) cohort / treatment arm, (b) cohort / study timepoint, (c) alpha diversity using the Shannon index, (d) taxonomic identity of the most abundant bacterial family (species the comprise the bacterial composition fall into 5 bacterial families: Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, Eubacteriaceae and Peptoniphilaceae. FIG. 13E shows the summed relative abundance of bacterial composition species.
[0050] FIGs. 14A-14B show fecal albumin concentrations are significantly reduced following treatment with the bacterial composition and with respect to a healthy comparator cohort. Timepoint is shown on the x-axis, fecal albumin concentration (pg / ml) is shown on the y-axis. The lower horizontal dashed line indicates assay LOD at 3.1 pg / ml, and upper horizontal dashed line indicates the 75th percentile of the healthy cohort. Numbers along x- axis represent samples per group, per timepoint. FIG. 14A shows fecal albumin concentrations in the bacterial composition treated (left bards) and placebo (right bars) arms across the peri-transplant period compared to a healthy cohort. Boxplots represent the distribution of fecal albumin concentrations in participants at each timepoint. FIG. 14B shows participant-level fecal albumin concentrations from baseline through HCT Day 0 when reduced placebo sample availability limits arm comparisons. Wald test p-values from linear models: * = p <0.05, *** = p <0.001.DETAILED DESCRIPTION OF THE DISCLOSURE
[0051] Provided herein are biomarkers and the use of such biomarkers in treating a bloodstream infection and / or gastrointestinal disease or condition in a subject in need thereof (e.g., a human subject undergoing allo-HSCT). As demonstrated herein, the concentration profile of the one or more biomarkers provided herein is associated with positive clinical outcome after administration of a bacterial composition to subjects undergoing allo-HSCT. Non-limiting examples of such positive clinical outcomes include: reduced incidence of bloodstream infections, reduced inflammation, improved mucosal / epithelial barrier integrity, reduced febrile neutropenia, and combinations thereof. Accordingly, the biomarkers provided herein are useful for various aspects of treating a bloodstream infection and / or gastrointestinal disease or condition. Additional aspects are provided throughout the present disclosure.I. Definitions
[0052] It is to be noted that the term "a" or "an" entity refers to one or more of that entity;for example, "a bacterial composition," is understood to represent one or more bacterial compositions. As such, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein.
[0053] Furthermore, "and / or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term "and / or" as used in a phrase such as " A and / or B" herein is intended to include " A and B," " A or B," " A" (alone), and " B" (alone). Likewise, the term "and / or" as used in a phrase such as " A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).
[0054] It is understood that wherever aspects are described herein with the language "comprising," otherwise analogous aspects described in terms of "consisting of" and / or "consisting essentially of" are also provided. As used herein, "comprising" is synonymous with "including," "containing," or "characterized by," and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. As used herein, "consisting of' excludes any element, step, or ingredient not specified in the claim element. As used herein, "consisting essentially of" does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.
[0055] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure is related.
[0056] Units, prefixes, and symbols are denoted in their Systeme International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, nucleotide sequences are written left to right in 5' to 3' orientation. Amino acid sequences are written left to right in amino to carboxy orientation. The headings provided herein are not limitations of the various aspects of the disclosure, which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.
[0057] The term "at least" prior to a number or series of numbers is understood to include the number adjacent to the term "at least," and all subsequent numbers or integers that couldlogically be included, as clear from context. For example, the number of nucleotides in a nucleic acid molecule must be an integer. For example, "at least 18 nucleotides of a 21- nucleotide nucleic acid molecule" means that 18, 19, 20, or 21 nucleotides have the indicated property. When at least is present before a series of numbers or a range, it is understood that "at least" can modify each of the numbers in the series or range. " At least" is also not limited to integers (e.g., "at least 5%" includes 5.0%, 5.1%, 5.18% without consideration of the number of significant figures.
[0058] As used herein, the term "approximately" or "about," as applied to one or more values of interest, refers to a value that is similar to a stated reference value and within a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). When the term "approximately" or "about" is applied herein to a particular value, the value without the term "approximately" or "about is also disclosed herein.
[0059] As described herein, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.
[0060] As used herein, the term "biomarker" refers to a marker that can be measured and evaluated as an indicator for a normal or abnormal biological process, disease, or condition. The term "marker" refers to any biological entity, including but not limited to a nucleic acid and / or protein. As described herein, some aspects of the present disclosure relate to determining the expression of one or more biomarkers of a subject, e.g., in administering a bacterial composition provided herein. Unless indicated otherwise, in some aspects, determining the expression of a biomarker comprises measuring the concentration of the biomarker (e.g., protein) present within a biological sample of a subject. In some aspects, determining the expression of a biomarker comprises quantifying the abundance of an associated gene (e.g., measuring the RNA level).
[0061] The terms "treat," "treating," and "treatment," as used herein, refer to any type of intervention or process performed on, or administering an active agent (e.g., any of the bacterial compositions provided herein) to a subject with the objective of reversing,alleviating, ameliorating, inhibiting, preventing, or slowing down the progression, development, severity or recurrence of a symptom, complication, condition or biochemical indicia associated with a disease or condition described herein (e.g., bloodstream infection and / or gastrointestinal disease or condition). As further described herein, in some aspects, treating a disease or disorder described herein (e.g., bloodstream infection) comprises reducing or preventing an incidence of an infection in a subject suffering from the disease or disorder. In some aspects, an efficacy of a treatment can be determined by evaluating signs and / or symptoms and according to whether induction of improvement and / or maintenance of an improved condition is achieved, e.g., for at least about one week, at least about two weeks, at least about three weeks, at least about four weeks, at least about five weeks, at least about six weeks, at least about seven weeks, at least about eight weeks, at least about nine weeks, at least about 10 weeks, at least about 11 weeks, at least about 12 weeks, at least about 13 weeks, at least about 14 weeks, at least about 15 weeks, at least about 16, weeks, at least about 17 weeks, or at least about 18 weeks. In some aspects, an efficacy of a treatment can be determined by evaluating signs and / or symptoms and according to whether induction of improvement and / or maintenance of an improved condition is achieved for at least about 100 days. A non-limiting example of indicators of therapeutic efficacy include engraftment of at least one bacterial species present in a bacterial composition (such as that described herein), for example, at about two weeks, at about three weeks, at about four weeks, at about five weeks, at about six weeks, at about seven weeks, at about eight weeks, at about nine weeks, at about 10 weeks, at about 11 weeks, at about 12 weeks, at about 13 weeks, at about 14 weeks, at about 15 weeks, at about 16 weeks, at about 17 weeks, at about 18 weeks, or longer after initial administration. In some aspects, an indicator of therapeutic efficacy comprises engraftment of at least one bacterial species present in a bacterial composition at about 100 days after initial administration. In some aspects, an additional indicator of therapeutic efficacy comprises a reduction in the abundance of pathogenic bacteria (e.g., ESKAPE pathogens including: Enterococcus fctecium. Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. or pathogens related to gastrointestinal infections, including Clostridioides difficile, viral, and parasitic infections), for example, at about two weeks, at about three weeks, at about four weeks, at about five weeks, at about six weeks, at about seven weeks, at about eight weeks, at about nine weeks,at about 10 weeks, at about 11 weeks, at about 12 weeks, at about 13 weeks, at about 14 weeks, at about 15 weeks, at about 16 weeks, at about 17 weeks, at about 18 weeks, or longer after initial administration of a bacterial composition. In some aspects, an indicator of therapeutic efficacy comprises a reducing in the abundance of pathogenic bacteria at about 100 days after initial administration. In some aspects, an indicator of therapeutic efficacy comprises a reduction in the abundance of at least one species identified herein (e.g., Enterococcus spp. and Enterobacteriaceae spp. in stool, drug resistant or multi-drug resistant organisms (MDROs) including vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), drug resistant or multi-drug resistant Enterobacteriaceae, methicillin resistant Staphylococcus aureus (MRSA), and organisms that produce extended- spectrum beta-lactamase (ESBL)), for example, at about two weeks, at about three weeks, at about four weeks, at about five weeks, at about six weeks, at about seven weeks, at about eight weeks, at about nine weeks, at about 10 weeks, at about 11 weeks, at about 12 weeks, at about 13 weeks, at about 14 weeks, at about 15 weeks, at about 16 weeks, at about 17 weeks, at about 18 weeks, or longer after initial administration of a bacterial composition. In some aspects, an indicator of therapeutic efficacy comprises a reduction in the abundance of at least one species identified herein (e.g., Enterococcus spp. and Enterobacteriaceae spp. in stool, drug resistant or multi-drug resistant organisms (MDROs) including vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), drug resistant or multi-drug resistant Enterobacteriaceae, methicillin resistant Staphylococcus aureus (MRSA), and organisms that produce extended-spectrum beta-lactamase (ESBL)) at least about 100 days after initial administration.
[0062] The terms "prevent," "preventing," and "prevention," as used herein, refer to partially or completely delaying onset of a disease or disorder described herein (e.g., bloodstream infection and / or gastrointestinal disease or condition); partially or completely delaying onset of one or more symptoms, features, or clinical manifestations of the disease or disorder described herein; partially or completely delaying onset of one or more symptoms, features, or manifestations of the disease or disorder described herein; partially or completely delaying progression of the disease or disorder described herein; and / or decreasing the risk of developing pathology associated with the disease or disorder described herein. In some aspects, any of the bacterial compositions provided herein canhelp prevent the incidence of an infection (e.g., bloodstream infection) in a subject in need thereof. As further described herein, in some aspects, by preventing the incidence of an infection, a bacterial composition provided herein can help treat a disease or disorder in the subject.
[0063] The term "microbiota" refers to the ecological community of microorganisms that occur (sustainably or transiently) in and on an animal subject, typically a mammal such as a human, including eukaryotes, archaea, bacteria, and viruses (including bacterial viruses i.e., phage).
[0064] The term "microbiome" refers to the genetic content of the communities of microbes that live in and on the human body, both sustainably and transiently, including eukaryotes, archaea, bacteria, and viruses (including bacterial viruses (i.e., phage)), wherein "genetic content" includes genomic DNA, RNA such as ribosomal RNA, the epigenome, plasmids, and all other types of genetic information.
[0065] The term "16S sequencing" or "16S rDNA" or "16S" refers to sequence derived by characterizing the nucleotides that comprise the 16S ribosomal RNA gene(s). The bacterial 16S rDNA is approximately 1500 nucleotides in full length and can be referred to fragments ranging from a few nucleotides to full length of the 16S rDNA. 16S rDNA is used in reconstructing the evolutionary relationships and sequence similarity of one bacterial isolate to another using phylogenetic approaches. 16S sequences are used for phylogenetic reconstruction as they are in general highly conserved, but contain specific hypervariable regions that harbor sufficient nucleotide diversity to differentiate genera and species of most bacteria.
[0066] The term " VI -V9 regions" of the 16S rRNA refers to the first through ninth hypervariable regions of the 16S rRNA gene that are used for genetic typing of bacterial samples. These regions in bacteria are defined by nucleotides 69-99, 137-242, 433-497, 576-682, 822-879, 986-1043, 1117-1173, 1243-1294 and 1435-1465 respectively using numbering based on the A. coli system of nomenclature. Brosius et al., Complete nucleotide sequence of a 16S ribosomal RNA gene from Escherichia coli, PNAS 75(10):4801-4805 (1978). In some aspects, a sequence comprising at least one of the VI, V2, V3, V4, V5, V6, V7, V8, and V9 regions is used to characterize an OTU. In some aspects, a sequence comprising at least all of the VI, V2, V3, V4, V5, V6, V7, V8, and V9 regions is used to characterize an OTU. In some aspects, a sequence comprising the VI,V2, and V3 regions is used to characterize an OTU. In some aspects, a sequence comprising the V3, V4, and V5 regions is used to characterize an OTU. In some aspects, a sequence comprising the V3, and V4 regions is used to characterize an OTU. In some aspects, a sequence comprising the V4, and V5 regions is used to characterize an OTU. In some aspects, a sequence comprising the V4 region is used to characterize an OTU. A person of ordinary skill in the art can identify the specific hypervariable regions of a candidate 16S rRNA by comparing the candidate sequence in question to a reference sequence and identifying the hypervariable regions based on similarity to the reference hypervariable regions, or alternatively, one can employ Whole Genome Shotgun (WGS) sequence characterization of microbes or a microbial community.
[0067] The term "engraftment" refers to the establishment of a bacterial species in a target niche that are absent or undetectable in a treated subject prior to treatment. The microbes comprising the engrafted ecology are present in the microbial composition and establish as constituents of the subject's microbial ecology. Engrafted species can establish for a transient period of time, or demonstrate long-term stability in the microbial ecology that populates the subject post treatment with a microbial composition. Without committing to any theory, the drug product ( / .<., bacterial compositions disclosed herein) can catalyze a shift from a dysbiotic ecology to one representative of a healthy state, either by engraftment of drug product species, promoting ecological conditions favorable for the growth of nonproduct commensal microbes present in the subject (augmentation), or both.
[0068] As used herein, engraftment is indicated by one or more of the following outputs:(i) strain level engraftment, (ii) species-level population engraftment, (iii) species-level subject engraftment, and (iv) putative engraftment. " Strain level engraftment" is determined using any relevant method known in the art. In some aspects, strain level engraftment is determined using an assay in which single nucleotide variant (SNV) frequencies unique to the drug product composition are used to determine whether strains of species detected in treated subjects are significantly more similar to strains in the composition compared to strains of species detected in subjects prior to treatment. Strain level engraftment is measured on a per-subject and per-species basis. Non-limiting examples of other methods of determining strain level engraftment include the use of probes, e.g., NanoString nCounter probes that can be targeted to unique regions of the strain genome, relative to other known genomic sequences of the same species, or compared tometagenomics datasets from healthy subjects; or specific PCR probes for the particular species or strain of interest. " Species-level population engraftment" refers to significantly increased prevalence (p <= 0.05) of a species in treated subjects relative to non-treated subjects at any post-treatment time point as measured with a Fisher's exact test, with the requirement that the species was not detected in treated subjects prior to treatment but was detected in the composition. Species-level population engraftment is a population-level measure and requires a significant (p <= 0.05) difference across the population treated with a particular regimen compared to placebo. " Species-level subject engraftment" refers to the detection of a species present in a bacterial composition in a subject post-treatment when said species was not detected pre-treatment in that subject. " Putative engraftment" refers to significantly increased prevalence (p <= 0.05) of a species in treated subjects relative to non-treated subjects at any post-treatment time point as measured with a Fisher's exact test. The putative engraftment further requires that the species was detected in the drug product composition and may or may not be present in the treated subject prior to treatment. " Putative engraftment" is a population level statistic. Putative engraftment can be further evaluated using strain level metrics for engraftment.
[0069] In some aspects, the term engraftment can be further divided into long-term engraftment and transient engraftment. " Long-term engraftment" refers to the ability of bacterial species or strains disclosed herein to durably reside in the gastrointestinal tracts of subjects after treatment. Such species or strains are described herein as "long-term engrafter" (LTE). In some aspects, long-term engrafters continue to be present in the subject (e.g., in the gastrointestinal tract) for about 4 weeks, about 8 weeks, about 12 weeks or longer after the start of dosing of a bacterial composition disclosed herein. " Transient engraftment" refers to the ability of bacterial species or strains e.g., those disclosed herein) to reside in the gastrointestinal tracts of subjects after treatment, but are only detected in the fecal samples of subjects for a limited period of time. In some aspects, if bacteria or combinations of bacteria are detected in the fecal sample of a subject, it is generally believed that those bacteria or combinations of bacteria remain present within the gastrointestinal tract. Such species or strains are described herein as "transient engrafter" (TE). In some aspects, transient-engrafters are detected at one or more time points and not detected at another time point. In some aspects, transient-engrafters are no longer detected in the subject (e.g., no longer detected in the fecal sample of the subject) about 1 week,about 2 weeks, or about 4 weeks after the start of dosing ( / .<., administering a bacterial composition disclosed herein).
[0070] The term "dysbiosis" refers to a state of the microbiota of the GI tract or other body area in a subject, including mucosal or skin surfaces in which the normal diversity and / or function of the ecological network is disrupted. Accordingly, the terms dysbiosis and "disruption" are used interchangeably herein. This unhealthy state can be due to a decrease in diversity, the overgrowth of one or more pathogens or pathobionts, symbiotic organisms able to cause disease only when certain genetic and / or environmental conditions are present in a subject, or the shift to an ecological microbial network that no longer provides an essential function to the host subject, and therefore no longer promotes health.
[0071] Identification of and reference to bacterial species described herein can be found throughout the present disclosure, including the Figures / Dra wings, Tables, and Sequence Listing. Where a taxonomic name is used or referenced for a specific bacterium, it is understood that the bacterium may have previously had a different taxonomic name(s) and that one of skill in the art would have resources available to identify and associate previous taxonomic names with those described herein, as used in the art, or both. Such resources include, but are not limited to, Bergey’s Manual of Systematics of Archea and Bacteria (1stEd.); Bergey’s Manual of Systematic Bacteriology (2ndEd.); the online version available at onlinelibrary.wiley. com / doi / book / 10.1002 / 9781118960608; and the National Center for Biotechnology Information (NCBI) database available online at www.ncbi.nlm.nih.gov / taxonomy.
[0072] As used herein, the terms "purify", "purified" and "purifying" refer to the state of a population (e.g., a plurality of known or unknown amount and / or concentration) of desired bacteria or bacterial spores, that have undergone one or more processes of purification, e.g., a selection or an enrichment of the desired bacterium and / or bacterial spores, or alternatively a removal or reduction of residual habitat products as described herein. In some aspects, a purified population has no detectable undesired activity or, alternatively, the level or amount of the undesired activity is at or below an acceptable level or amount. In some aspects, a purified population has an amount and / or concentration of desired bacteria or bacterial spores, e.g, in general or of selected species, at or above an acceptable amount and / or concentration. In some aspects, the ratio of desired-to-undesired activity (e.g., spores compared to vegetative bacteria), has changed by about 2-fold, about 5-fold,about 10-fold, about 30-fold, about 100-fold, about 300-fold, about l*104, about l*105, about l*106, about l*107, about l*108, or greater than about l*108. In some aspects, a purified population of bacterial spores is enriched as compared to the starting material (e.g., a fecal material) from which the population is obtained. This enrichment can be by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.9%, about 99.99%, about 99.999%, about 99.9999%, about 99.99999%, or greater than about 99.999999% as compared to the starting material.
[0073] As used herein, the terms "subject," "individual," and "patient" can be used interchangeably and refer to any animal subj ect including humans, laboratory animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs, turkeys, and chickens), and household pets (e.g., dogs, cats, and rodents). As is evident from the present disclosure, a subject as described herein suffers from a disease or condition (e.g., bloodstream infection and / or a gastrointestinal disease or condition). In some aspects, a subject provided herein suffers from a bloodstream infection. In some aspects, a subject suffers from an immunodeficiency. In some aspects, a subject suffers from a non-bloodstream infection. In some aspects, a subject suffers from a dysbiosis or disruption of the gastrointestinal microbiota. In some aspects, a subject suffers from a disease or condition associated with an anti-cancer therapy (e.g., radiation, chemotherapy, or both). In some aspects, a subject suffers from a disease or condition associated with an adoptive cell therapy (e.g., an allogeneic or autologous stem cells and / or CAR T cells). A non-limiting example of a disease or condition associated with an adoptive cell therapy comprises a graft-versus-host- disease (GvHD). In some aspects, a subject suffers from two or more of the following: a bloodstream infection, an immunodeficiency, a non-bloodstream infection, a dysbiosis or disruption of the gastrointestinal microbiota, a disease or condition associated with an anticancer therapy (e.g., radiation and / or chemotherapy), a disease or condition associated with adoptive cell therapy (e.g., an allogeneic or autologous stem cells and / or CAR T cells), or combinations thereof. As demonstrated herein, in some aspects, a subject provided herein will undergo, has undergone, or is undergoing a hematopoietic stem cell transplantation.
[0074] As used herein, the term "hematopoietic stem cells" (HSCs) refers to a subset of multipotent stem cells that give rise to all the blood or immune cell types, including myeloid (e.g., monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes,megakaryocytes / platelets, dendritic cells, mast cells), and lymphoid lineages (e.g., innate lymphoid cells, T -cells, B-cells, NKT -cells, NK-cells), and having multi-lineage hematopoietic differentiation potential and sustained self-renewal activity. The term "stem cells," as used herein, refers to cells that retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types.
[0075] As used herein, the term "hematopoietic stem cell transplantation" (HSCT) refers to the transplantation of multipotent hematopoietic stem cells from a donor to a recipient. In an "autologous" HSC transplantation (aHSCT), the stem cells are isolated from a subject in need of a treatment (e.g., chemotherapy or radiation therapy) and then administered back to the subject after the treatment. Therefore, in the context of autologous HSC transplantation, the terms "donor" and "recipient" / "subject" refer to the same individual. In a "syngeneic" HSC transplantation, stem cells are isolated from an identical twin of the subject to be treated and then administered to the subject after treatment (e.g., chemotherapy or radiation therapy). In an "allogenic" HSC transplantation (allo-HSCT), stem cells are isolated from a healthy donor (e.g., non-identical twin or an individual related or not related to the subject to be treated) and then administered to a different recipient subject after treatment (e.g., chemotherapy or radiation therapy). In such transplantations, the terms "donor" and "subject" / "recipient" refer to different individuals. Unless specified otherwise, the term HSCT is not limited to any specific type of HSCT (e.g., encompasses autologous, syngeneic, and allogenic HSCT).
[0076] As used herein, the term "gastrointestinal disease or condition" refers to any disease or condition that involves a disruption of the microbiota within the gastrointestinal tract (e.g., mouth, esophagus, stomach, small intestine, large intestine, and / or rectum) of a subject.
[0077] As used herein, the term "bloodstream infection" refers to a disease where the infectious agent (e.g., microbial pathogen) is present in the bloodstream of the subject. Nonlimiting examples of microbial pathogens that can be associated with a bloodstream infection include: ESKAPE pathogens (e.g., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sppf, with Enterococcus species including but not limited to Enterococcus faecalis and Enterococcus faecium, Enterobacteriaceae species including but not limited to Klebsiella pneumonia, or such species that are resistant to vancomycin or carbapenems,with drug resistant or multi-drug resistant organisms (MDROs) including VRE, CRE (including Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella aerogenes, Enterococcus species), with drug resistant or multi-drug resistant Enterobacteriaceae, with extended spectrum beta-lactamase (ESBLs) producing bacteria (including E. coli, Klebsiella species), or with methicillin-resistant Staphylococcus aureus (MRSA). In some aspects, the bloodstream infection comprises an infection with an ESKAPE pathogen. In some aspects, the bloodstream infection comprises an opportunistic infection with a commensal bacterial species. In some aspects, the bloodstream infection comprises an infection with an antibiotic resistant bacterial species. In some aspects, a subject can suffer from both a bloodstream infection and a gastrointestinal disease or condition.
[0078] As used herein, the term "plurality of bacteria" refer to a combination of two or more bacteria. A "combination" of two or more bacteria includes the physical co-existence of the two bacteria, either in the same material or product or in physically connected products, as well as the temporal co-administration or co-localization of the two bacteria.
[0079] For nucleic acids, the term "substantial homology" indicates that two nucleic acids, or designated sequences thereof, when optimally aligned and compared, are identical, with appropriate nucleotide insertions or deletions, in at least about 80% of the nucleotides, at least about 90% to 95%, or at least about 98% to 99.5% of the nucleotides. In some aspects, two nucleic acids (e.g., 16S rDNA sequences) share substantial homology if they have a sequence identity of at least about 95%, at least about 95.5%, at least about 96%, at least about 96.5%, at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99%, at least about 99.1%, at least about 99.2%, at least about 99.3%, at least about 99.4%, at least about 99.5%, at least about 99.6%, at least about 99.7%, at least about 99.8%, or at least about 99.9%. In some aspects, bacteria which share substantial homology in their 16S rDNA sequence can be considered to be the same species. In some aspects, bacteria that are the same species share one or more functional properties (e.g., described herein). Alternatively, substantial homology exists when the segments will hybridize under selective hybridization conditions, to the complement of the strand.
[0080] For polypeptides, the term "substantial homology" indicates that two polypeptides, or designated sequences thereof, when optimally aligned and compared, are identical, with appropriate amino acid insertions or deletions, in at least about 80% of the amino acids, at least about 90% to 95%, or at least about 98% to 99.5% of the amino acids.
[0081] The percent identity between two sequences is a function of the number of identical positions shared by the sequences (i.e., % homology = # of identical positions / total # of positions x 100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm, as described in the non-limiting examples below.
[0082] The percent identity between two nucleotide sequences can be determined using the GAP program in the GCG software package (available at worldwideweb.gcg.com), using a NWSgapdna. CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. The percent identity between two nucleotide or amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (CABIOS, 4: 11-17 (1989)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (J Mol. Biol. (48):444-453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package (available at worldwideweb.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.
[0083] The nucleic acid and protein sequences described herein can further be used as a "query sequence" to perform a search against public databases to, for example, identify related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to the nucleic acid molecules described herein. BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to the protein molecules described herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul etal., (1997) Nucleic Acids Res. 25(17):3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. Seeworldwideweb.ncbi.nlm.nih.gov. Other methods of determining identity that are known in the art can be used.
[0084] As used herein, the terms "ug" and "uM" are used interchangeably with "pg" and "pM," respectively.IL Biomarkers
[0085] As demonstrated herein, Applicant has identified that subjects who favorably respond to a composition comprising a plurality of bacteria (also referred to herein as "bacterial composition") exhibit certain expression profile of one or more biomarkers. For instance, as compared to a reference subject, a subject who favorably responds to a bacterial composition exhibits an altered expression profile of the one or more biomarkers. As used herein, the term "reference subject" comprises (a) a corresponding subject who did not favorably respond to the bacterial composition, (b) a corresponding subject who did not receive an administration of the bacterial composition, or (c) both (a) and (b). As used herein, the term "favorably respond" (or variants thereof) refers to the exhibiting of one or more therapeutic effects after administration of a bacterial composition provided herein. For instance, in some aspects, a subject favorably responds to abacterial composition where one or more symptoms of a disease or condition (e.g., bloodstream infection and / or gastrointestinal disease or condition) is reduced in the subject after the administration. Nonlimiting examples of therapeutic effects include: a reduced incidence of a bloodstream infection, reduced inflammation (e.g., within the gastrointestinal tract of the subject), improved mucosal / epithelial barrier integrity, or combinations thereof. Where the disease or condition comprises a bloodstream infection, in some aspects, a subject favorably responds to a bacterial composition if the risk and / or incidence of the bloodstream infection is reduced in the subject.
[0086] In some aspects, a biomarker useful for the present disclosure comprises one or more of the markers listed in Table 1. In some aspects, the biomarker is a marker of mucosal / epithelial gut barrier integrity. Non-limiting examples of such markers include: elafin, CK-18, HGF, TIM3, fecal albumin, or combinations thereof. In some aspects, the biomarker is a marker of gastrointestinal inflammation. Non-limiting examples of such markers include: Reg3a, CXCL10, IFN-y, calprotectin, lactoferrin, myeloperoxidase, or combinations thereof. In some aspects, the biomarker is a marker of systemic inflammation. Non-limiting examples of such markers include: sST2, TNF-a, TNFR1, IL-6, IL-8, IL-15,IL-17, IL-10, IFN-y, CXCL10, MCP-1, CD45, CD8, CD45RO, a4p7, or combinations thereof. In some aspects, the biomarker is a marker of immune-modulation. Non-limiting examples of such markers include: IL2Ra (CD25), IL-6, IL-8, TIM3, IL-7, IL-15, IL-17, IFN-y, CD45, CD4, CD146, Foxp3, CD8, CCR5, a4p7, or combinations thereof. In some aspects, the biomarker is a marker of tissue / organ injury. Non-limiting examples of such markers include: sST2, IL-8, CK-18, HGF, elafin, IL-17, IFN-y, or combinations thereof.
[0087] In some aspects, the biomarker comprises fecal albumin. In some aspects, the biomarker comprises myeloperoxidase. In some aspects, the biomarker comprises TNFR1. In some aspects, the biomarker comprises IL2Ra (CD25). In some aspects, the biomarker comprises elafin. In some aspects, the biomarker comprises CK-18. In some aspects, the biomarker comprises HGF. In some aspects, the biomarker comprises CD 146. In some aspects, the biomarker comprises CCR5. In some aspects, the biomarker comprises a4p7. In some aspects, the biomarker comprises Reg3a. In some aspects, the biomarker comprises CXCL10. In some aspects, the biomarker comprises calprotectin. In some aspects, the biomarker comprises lactoferrin. In some aspects, the biomarker comprises Thl7. In some aspects, the biomarker comprises CD8. In some aspects, the biomarker comprise IL-6. In some aspects, the biomarker comprises IL-8. In some aspects, the biomarker comprises IL- 17. In some aspects, the biomarker comprises sST2. In some aspects, the biomarker comprises TNF-a. In some aspects, the biomarker comprises Hs-CRP. In some aspects, the biomarker comprises IFN-y. In some aspects, the biomarker comprises MCP1. In some aspects, the biomarker comprises IL-7. In some aspects, the biomarker comprises IL-10. In some aspects, the biomarker comprises Tregs. In some aspects, the biomarker comprises Tregs. In some aspects, the biomarker comprises TIM3. In some aspects, the biomarker comprises CD45. In some aspects, the biomarker comprises CD4. In some aspects, the biomarker comprises Foxp3. In some aspects, the biomarker comprises CD45RO. In some aspects, the biomarker comprises CCR5. In some aspects, the biomarker comprises a combination of CD45, CD4, CD25, and Foxp3. In some aspects, the biomarker comprises a combination of CD45, CD4, CD146, and CCR5. In some aspects, the biomarker comprises a combination of CD45, CD8, CD45RO, and a4p7.Table 1. Biomarkersfecal albumin CCR5 IL-6 IL-7myeloperoxidase a4p7 IL-8 IL-10TNFR1 Reg3a IL-17 TregsIL2Ra (CD25) CXCL10 sST2 TIM3elafin calprotectin TNF-a CD45CK-18 lactoferrin Hs-CRP CD4HGF Thl7 IFN-y Foxp3CD 146 CD8 MCP1 CD45ROCCR5
[0088] In some aspects, the biomarker comprises two of the markers listed in Table 1. In some aspects, the biomarker comprises three of the markers listed in Table 1. In some aspects, the biomarker comprises four of the markers listed in Table 1. In some aspects, the biomarker comprises five of the markers listed in Table 1. In some aspects, the biomarker comprises six of the markers listed in Table 1. In some aspects, the biomarker comprises seven of the markers listed in Table 1. In some aspects, the biomarker comprises eight of the markers listed in Table 1. In some aspects, the biomarker comprises nine of the markers listed in Table 1. In some aspects, the biomarker comprises 10 of the markers listed in Table 1. In some aspects, the biomarker comprises 11 of the markers listed in Table 1. In some aspects, the biomarker comprises 12 of the markers listed in Table 1. In some aspects, the biomarker comprises 13 of the markers listed in Table 1. In some aspects, the biomarker comprises 14 of the markers listed in Table 1. In some aspects, the biomarker comprises 15 of the markers listed in Table 1. In some aspects, the biomarker comprises 16 of the markers listed in Table 1. In some aspects, the biomarker comprises 17 of the markers listed in Table 1. In some aspects, the biomarker comprises 18 of the markers listed in Table 1. In some aspects, the biomarker comprises 19 of the markers listed in Table 1. In some aspects, the biomarker comprises 20 of the markers listed in Table 1. In some aspects, the biomarker comprises 21 of the markers listed in Table 1. In some aspects, the biomarker comprises 22 of the markers listed in Table 1. In some aspects, the biomarker comprises 23 of the markers listed in Table 1. In some aspects, the biomarker comprises 24 of the markers listed in Table 1. In some aspects, the biomarker comprises 25 of the markers listed in Table 1. In some aspects, the biomarker comprises 26 of the markers listed in Table 1. In some aspects, thebiomarker comprises 27 of the markers listed in Table 1. In some aspects, the biomarker comprises 28 of the markers listed in Table 1. In some aspects, the biomarker comprises 29 of the markers listed in Table 1. In some aspects, the biomarker comprises 30 of the markers listed in Table 1. In some aspects, the biomarker comprises 31 of the markers listed in Table 1. In some aspects, the biomarker comprises 32 of the markers listed in Table 1. In some aspects, the biomarker comprises all of the markers listed in Table 1.
[0089] In some aspects, as compared to a reference subj ect (e.g., corresponding subj ect that did not receive an administration of a bacterial composition), the expression of the biomarker is decreased in the subject. In some aspects, the expression of the biomarker is decreased by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100% as compared to the reference subject. In some aspects, as compared to a reference subject e.g., corresponding subject that did not receive an administration of a bacterial composition), the expression of the biomarker is increased in the subject. In some aspects, the expression of the biomarker is increased by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% as compared to the reference subject. In some aspects, the expression of the biomarker is increased by at least about 1.5-fold, at least about 2-fold, at least about 3- fold, at least about 4-fold, at least about 5-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, at least about 45-fold, or at least about 50-fold as compared to the reference subject.
[0090] In some aspects, the biomarker comprises fecal albumin and the expression of fecal albumin in the subject is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises elafin and the expression of elafin is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises Reg3a and the expression of Reg3a is altered (decreased or increased)as compared to the reference subject. In some aspects, the biomarker comprises CXCL10 and the expression of CXCL10 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-6 and the expression of IL- 6 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-8 and the expression of IL-8 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-17 and the expression of IL-17 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises TNF-a and the expression of TNF-a is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises Hs-CRP and the expression of Hs-CRP is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IFN-y and the expression of IFN-y is altered (decreased or increased) as compared to the reference subject.
[0091] In some aspects, the biomarker comprises IL2Ra and the expression of IL2Ra is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-7 and the expression of IL-7 is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-15 and the expression of IL-15 is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-10 and the expression of IL-10 is altered (increased or decreased) as compared to the reference subject.
[0092] As is evident from at least the above, in some aspects, a biomarker comprises a plurality of biomarkers. In some aspects, the plurality of biomarkers comprise a first biomarker and a second biomarker, wherein the first biomarker and the second biomarker are not the same, and wherein the expression of the first biomarker is increased as compared to a reference subject (e.g., corresponding subject that did not receive an administration of a bacterial composition) and the expression of the second biomarker is the same as the reference subject. In some aspects, the expression of the first biomarker is increased as compared to the reference subject and the expression of the second biomarker is increased as compared to the reference subject. In some aspects, the expression of the first biomarker is increased as compared to the reference subject and the expression of the second biomarker is decreased as compared to the reference subject. In some aspects, the expression of the first biomarker is the same as compared to the reference subject and theexpression of the second biomarker is increased as compared to the reference subject. In some aspects, the expression of the first biomarker is the same as compared to the reference subject and the expression of the second biomarker is decreased as compared to the reference subject. In some aspects, the expression of the first biomarker is decreased as compared to the reference subject and the expression of the second biomarker is the same as the reference subject. In some aspects, the expression of the first biomarker is decreased as compared to the reference subject and the expression of the second biomarker is increased as compared to the reference subject. In some aspects, the expression of the first biomarker is decreased as compared to the reference subject and the expression of the second biomarker is decreased as compared to the reference subject.
[0093] In some aspects, the expression of one or more biomarkers provided herein can be determined in a biological sample obtained from a subject. Non-limiting examples of biological samples include: a stool sample, a blood sample, a plasma sample, a serum sample, a urine sample, a sweat sample, a saliva sample, a tissue sample, or any combination thereof. In some aspects, the biological sample comprises a stool sample (also referred to herein as "fecal sample"). Non-limiting examples of biomarkers that can be measured in a stool sample include: albumin, calprotectin, lactoferrin, myeloperoxidase, or combinations thereof. In some aspects, the biological sample comprises a blood sample. In some aspects, the biological sample comprises a plasma sample. Non-limiting examples of biological markers that can be measured in a plasma or serum sample include: IL2Ra, sST2, Reg3a, TNF-a, TNFR1, IL-6, IL-8, TIM3, CK-18, HGF, elafin, IL-7, IL-15, IL-17, IL-10, IFN-y, CXCL10, MCP-1, Hs-CRP, or combinations thereof.III. Methods of the Disclosure
[0094] The one or more biomarkers provided above are useful in various aspects of treating a disease or condition in a subject (e.g., bloodstream infection and / or gastrointestinal disease or condition). Non-limiting examples of such diseases or conditions include: a bloodstream infection, an immunodeficiency, a non-bloodstream infection, a dysbiosis or disruption of the gastrointestinal microbiota, a disease or condition associated with an anticancer therapy (e.g., radiation and / or chemotherapy), a disease or condition associated with adoptive cell therapy (e.g., an allogeneic or autologous stem cells and / or CAR T cells), or combinations thereof. Additional examples of diseases or conditions include: acute leukemia (ALL), acute myelogenous leukemia (AML), multiple myeloma and lymphomas(NHL and HD), MDS (combined with MPNs) and related cancers that require HSCT, mucositis, infections including but not limited to blood and tissue infection with ESKAPE pathogens (including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enter obacter spp. with Enterococcus species including but not limited to Enterococcus faecalis and Enterococcus faecium, Enterobacteriaceae species including but not limited to Klebsiella pneumonia, or such species that are resistant to vancomycin or carbapenems, with drug resistant or multi-drug resistant organisms (MDROs) including VRE, CRE (including Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella aerogenes, Enterococcus species), with drug resistant or multi-drug resistant Enterobacteriaceae, with extended spectrum beta-lactamase (ESBLs) producing bacteria (including E. coli, Klebsiella species), or with methicillin-resistant Staphylococcus aureus (MRSA), patients at risk for infectious disease, including for example, patients in intensive care units and long-term care, treatment and prevention of C. difficile infection (CDI), as well as recurrent CDI, immune check point inhibitor-induced (ICI) colitis, viral infection and reactivation, and fungal infection, including gastrointestinal infection and systemic, e.g., candidemia, etc.). Additional examples of diseases or disorders are provided in U. S. Publ. No. 20210196766A1 and U. S. Publ. No. 20240000859A1, each of which is incorporated herein by reference in its entirety.
[0095] As demonstrated and described herein, subjects who respond favorably to a bacterial composition (such as that described herein) exhibit certain biomarker profile that is altered (increased or decreased) as compared to that of a reference subject (e.g., a corresponding subject who did not favorably respond to the bacterial composition and / or a corresponding subject who did not receive an administration of the bacterial composition).
[0096] Accordingly, some aspects of the present disclosure relate to a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria (bacterial composition), wherein the subject exhibits a biomarker, wherein the expression of the biomarker is altered (increased or decreased) as compared to a reference subject, wherein the reference subject comprises (a) a corresponding subject who did not favorably respond to the bacterial composition, (b) a corresponding subject who did not receive an administration of the bacterial composition, or (c) both (a) and (b), and wherein the biomarker comprises one or more of the markers listed in Table 1. In some aspects, thebiomarker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK- 18, HGF, CD146, CCR5, a4p7, or combinations thereof.
[0097] In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises fecal albumin and the expression of fecal albumin is altered (reduced or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises elafin and the expression of elafin is altered (reduced or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises Reg3a and the expression of Reg3a is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises CXCL10 and the expression of CXCL10 is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL-6 and the expression of IL-6 is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL-8 and the expression of IL-8 is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL-17 and the expression of IL-17 is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarkercomprises TNF-a and the expression of TNF-a is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises Hs-CRP and the expression of Hs-CRP is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IFN-y and the expression of IFN-y is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL2Ra and the expression of IL2Ra is altered (increased or decreased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL-7 and the expression of IL-7 is altered (increased or decreased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL- 15 and the expression of IL-15 is altered (increased or decreased) as compared to the reference subject. In some aspects, provided herein is a method of preventing and / or reducing a risk of bloodstream infection in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL- 10 and the expression of IL- 10 is altered (increased or decreased) as compared to the reference subject.
[0098] In some aspects, after the administering, the risk of bloodstream infection in the subject is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100% as compared to the reference subject. Insome aspects, preventing and / or reducing the risk of a bloodstream infection comprises reducing an incidence of the bloodstream infection in the subject. Accordingly, in some aspects, after the administering, the incidence of a bloodstream infection in the subject is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100% as compared to the reference subject.
[0099] In some aspects, the present disclosure relates to a method of reducing and / or preventing a pathogen domination within the gastrointestinal tract of a subject in need thereof. As used herein, the term "pathogen domination" refers to a condition where a pathogen (e.g., pathogenic bacteria) overpopulates the gut or other areas of the body. In some aspects, pathogen domination occurs where the pathogenic bacteria make up more than about 5%, more than about 10%, more than about 15%, more than about 20%, more than about 25%, or more than about 30% of the microbiota. In some aspects, pathogen domination occurs where 30% or greater of the microbiome is made up of one of the four taxonomic families: Streptococcaceae, Staphylococcaceae, Enterococcaceae, and Enterobacteriaceae.
[0100] Accordingly, also provided herein is a method of reducing and / or preventing a pathogen domination within the gastrointestinal tract of a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the subject exhibits a biomarker, wherein the expression of the biomarker is altered (increased or decreased) as compared to a reference subject, wherein the reference subject comprises (a) a corresponding subject who did not favorably respond to the bacterial composition, (b) a corresponding subject who did not receive an administration of the bacterial composition, or (c) both (a) and (b), and wherein the biomarker comprises one or more of the markers listed in Table 1. In some aspects, the biomarker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof. In some aspects, the biomarker comprises fecal albumin and the expression of fecal albumin in the subject is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises elafin and the expression of elafin is altered (decreased or increased) as compared to the reference subject. In someaspects, the biomarker comprises Reg3a and the expression of Reg3a is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises CXCL10 and the expression of CXCL10 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-6 and the expression of IL-6 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-8 and the expression of IL-8 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-17 and the expression of IL-17 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises TNF-a and the expression of TNF-a is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises Hs-CRP and the expression of Hs-CRP is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IFN-y and the expression of IFN-y is altered (decreased or increased) as compared to the reference subject, the biomarker comprises IL2Ra and the expression of IL2Ra is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-7 and the expression of IL-7 is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-15 and the expression of IL-15 is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-10 and the expression of IL-10 is altered (increased or decreased) as compared to the reference subject.
[0101] In some aspects, reducing a pathogen domination comprises reducing the abundance of a pathogen within the gastrointestinal tract of a subject. Accordingly, in some aspects, after the administering, the abundance of a pathogen is reduced within the gastrointestinal tract of the subject by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100% as compared to the reference subject. In some aspects, after the administering, the pathogen is no longer detectable within the gastrointestinal tract of the subject. In some aspects, after the administering, the quantitative abundance of the pathogen within the gastrointestinal tract of the subject isreduced by at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 10-fold, at least about 15-fold, at least about 20- fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40- fold, at least about 45-fold, at least about 50-fold, at least about 75-fold, at least about 100- fold, at least about 150-fold, at least about 200-fold, at least about 250-fold, at least about 300-fold, at least about 350-fold, at least about 400-fold, at least about 450-fold, at least about 500-fold, at least about 550-fold, at least about 600-fold, at least about 650-fold, at least about 700-fold, at least about 750-fold, at least about 800-fold, at least about 850-fold, at least about 900-fold, at least about 950-fold, or at least about 1,000-fold.
[0102] Some aspects of the present disclosure relate to methods of repairing and / or protecting a gut epithelial barrier integrity in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the subject exhibits a biomarker, wherein the expression of the biomarker is altered (increased or decreased) as compared to a reference subject, wherein the reference subject comprises (a) a corresponding subject who did not favorably respond to the bacterial composition, (b) a corresponding subject who did not receive an administration of the bacterial composition, or (c) both (a) and (b), and wherein the biomarker comprises one or more of the markers listed in Table 1. In some aspects, provided herein is a method of repairing and / or protecting a gut epithelial barrier integrity in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the subject exhibits a biomarker selected from fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof, wherein the expression of the biomarker is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises fecal albumin and the expression of fecal albumin in the subject is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises elafin and the expression of elafin is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises Reg3a and the expression of Reg3a is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises CXCL10 and the expression of CXCL10 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-6 and the expression of IL-6 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-8 andthe expression of IL-8 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL-17 and the expression of IL-17 is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises TNF-a and the expression of TNF-a is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises Hs-CRP and the expression of Hs-CRP is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IFN-y and the expression of IFN-y is altered (decreased or increased) as compared to the reference subject. In some aspects, the biomarker comprises IL2Ra and the expression of IL2Ra is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-7 and the expression of IL-7 is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-15 and the expression of IL- 15 is altered (increased or decreased) as compared to the reference subject. In some aspects, the biomarker comprises IL-10 and the expression of IL-10 is altered (increased or decreased) as compared to the reference subject.
[0103] In some aspects, after the administering, the integrity of the gut epithelial barrier is increased by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% as compared to the reference subject. In some aspects, after the administering, the integrity of the gut epithelial barrier is increased by at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, at least about 45-fold, or at least about 50-fold as compared to the reference subject.
[0104] Some aspects of the present disclosure are related to a method of regulating an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition wherein the subject exhibits a biomarker, wherein the expression of the biomarker is altered (increased or decreased) as compared to a reference subject, wherein the reference subject comprises (a) a corresponding subject who did not favorably respond to the bacterial composition, (b) a corresponding subject who did not receive anadministration of the bacterial composition, or (c) both (a) and (b), and wherein the biomarker comprises one or more of the markers listed in Table 1.
[0105] As demonstrated herein, administering a bacterial composition described herein to a subject (e.g., undergoing allo-HSCT) can reduce an inflammatory response in a subject. Accordingly, in some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering a bacterial composition to the subject, wherein the subject exhibits a biomarker selected from fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof, wherein the expression of the biomarker is altered (increased or decreased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises fecal albumin and the expression of fecal albumin in the subject is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises elafin and the expression of elafin is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises Reg3a and the expression of Reg3a is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises CXCL10 and the expression of CXCL10 is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL- 6 and the expression of IL-6 is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, and wherein the biomarker comprises IL-8 and the expression of IL-8 is altered (decreased or increased) as compared to the reference subject. In some aspects, amethod of reducing an inflammatory response in a subject in need thereof comprises administering a bacterial composition to the subject, wherein the biomarker comprises IL- 17 and the expression of IL-17 is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises TNF-a and the expression of TNF-a is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises Hs-CRP and the expression of Hs-CRP is altered (decreased or increased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IFN- y and the expression of IFN-y is altered (decreased or increased) as compared to the reference subject. Also provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL2Ra and the expression of IL2Ra is altered (increased or decreased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL-7 and the expression of IL-7 is altered (increased or decreased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL-15 and the expression of IL- 15 is altered (increased or decreased) as compared to the reference subject. In some aspects, provided herein is a method of reducing an inflammatory response in a subject in need thereof, comprising administering to the subject a bacterial composition, wherein the biomarker comprises IL-10 and the expression of IL-10 is altered (increased or decreased) as compared to the reference subject.
[0106] In some aspects, after the administering, the inflammatory response in the subject is reduced. In some aspects, the inflammatory response in the subject is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%,at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100% as compared to the reference subject. In some aspects, an inflammatory response comprises a systemic inflammation. Accordingly, in some aspects, after the administering, a systemic inflammation in the subject is reduced, e.g., by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%, as compared to the reference subject. In some aspects, an inflammatory response comprises a local gastrointestinal inflammation. Accordingly, in some aspects, after the administering, a local gastrointestinal inflammation in the subject is reduced, e.g., by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%, as compared to the reference subject. In some aspects, an inflammatory response comprises both a systemic inflammation and a local gastrointestinal inflammation. In some aspects, after the administering, both a systemic inflammation and a local gastrointestinal inflammation is reduced in the subject, e.g., by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%, as compared to the reference subject. An inflammatory response in a subject can be measured by any suitable methods known in the art.
[0107] As is evident from the present disclosure, bacterial compositions provided herein can modulate the expression of one or more biomarkers when administered to a subject. In some aspects, administering a bacterial composition provided herein can increase the expression of a biomarker where the expression of the biomarker is low in a reference subject (e.g., corresponding subject suffering from a blood stream infection and / orgastrointestinal disease or condition and did not receive an administration of a bacterial composition provided herein). In some aspects, after the administering, expression of the biomarker is increased in the subject by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% as compared to the reference subject. In some aspects, after the administering, expression of the biomarker is increased by at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 10-fold, at least about 15-fold, at least about 20- fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40- fold, at least about 45-fold, or at least about 50-fold as compared to the reference subject. As demonstrated herein, in some aspects, a biomarker comprises IL- 10 and the expression of IL- 10 is increased in the subject after the administration of a bacterial composition provided herein.
[0108] In some aspects, administering a bacterial composition provided herein can reduce the expression of a biomarker where the expression of the biomarker is high in a reference subject (e.g., corresponding subject suffering from a bloodstream infection and / or gastrointestinal disease or condition and did not receive an administration of a bacterial composition provided herein). In some aspects, after the administering, expression of the biomarker is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100% as compared to the reference subject. In some aspects, a biomarker comprises fecal albumin and the expression of fecal albumin is reduced in the subject after the administration of a bacterial composition provided herein. In some aspects, a biomarker comprises elafin and the expression of elafin is reduced in the subject after the administration of a bacterial composition. In some aspects, a biomarker comprises Reg3a and the expression of Reg3a is reduced in the subject after the administration of abacterial composition. In some aspects, a biomarker comprises CXCL10 and the expression of CXCL10 is reduced in the subject after the administration of abacterial composition. In some aspects, a biomarker comprises IL-8 and the expression of IL-8 is reduced after the administration of a bacterial composition. In some aspects, a biomarker comprises IL-17 and the expression of IL-17 is reduced after the administration of a bacterial composition. In some aspects, a biomarker comprises TNF-a and the expression of TNF-a is reduced after the administration of a bacterial composition.
[0109] In some aspects, by measuring the expression of one or more biomarkers provided herein, it is possible to identify subjects (e.g., undergoing allo-HSCT) that are responding to an administration of a bacterial composition provided herein. In some aspects, a subject is responding to the bacterial composition if the subject exhibits one or more therapeutic effects (e.g., reduction in one or more symptoms of a blood stream infection and / or gastrointestinal disease or condition) after the administration. Non-limiting examples of therapeutic effects include: a reduced incidence of a bloodstream infection, reduced inflammation (e.g., within the gastrointestinal tract of the subject), improved mucosal / epithelial barrier integrity, or combinations thereof.
[0110] Accordingly, some aspects of the present disclosure relates to a method of identifying a subject who is responding to a bacterial composition provided herein, comprising: determining the expression of a biomarker in a biological sample obtained from the subject, wherein the biomarker comprises one or more of the markers listed in Table 1, wherein prior to the determining, the subject received an administration of the bacterial composition, and wherein the subject is responding to the bacterial composition if the expression of the biomarker is altered (increased or decreased) as compared to a reference subject (e.g., corresponding subject that did not receive an administration of the bacterial composition). In some aspects, a method of identifying a subject who is responding to a bacterial composition provided herein comprises: (a) administering the bacterial composition to a subject, and (b) determining the expression of a biomarker in a biological sample obtained from the subject, wherein the biomarker comprises one or more of the markers listed in Table 1, and wherein the subject is responding to the bacterial composition if the expression of the biomarker is altered (increased or decreased) as compared to a reference subject (e.g., corresponding subject that did not receive an administration of the bacterial composition). In some aspects, the subject is responding to the bacterial composition if the expression of the biomarker is altered (increased or decreased) by at least about 5%, at least about 10%, at least about 15%, at least about 20%,at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% as compared to the reference subject. In some aspects, the subject is responding to the bacterial composition if the expression of the biomarker is altered by at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30-fold, at least about 35-fold, at least about 40-fold, at least about 45-fold, or at least about 50-fold as compared to the reference subject.[OHl] In some aspects, a subject is responding to a bacterial composition if the expression of a biomarker is altered (increased or decreased) as compared to a reference subject (e.g., corresponding subject that did not receive an administration of the bacterial composition), wherein the biomarker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof. In some aspects, the subject is responding to a bacterial composition if the expression of fecal albumin in the subject is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of elafin is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of Reg3a is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of CXCL10 is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of IL-6 is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of IL-8 is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of TNF-a is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of Hs-CRP is altered (decreased or increased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of IFN-y is altered (decreased or increased) as compared to the reference subject.In some aspects, the subject is responding to a bacterial composition if the expression of IL2Ra is altered (increased or decreased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of IL-7 is altered (increased or decreased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of IL- 15 is altered (increased or decreased) as compared to the reference subject. In some aspects, the subject is responding to a bacterial composition if the expression of IL-10 is altered (increased or decreased) as compared to the reference subject.
[0112] In some aspects, where the subject is responding to a bacterial composition, one or more additional doses of the bacterial composition are administered to the subject.
[0113] Some aspects of the present disclosure also relate to a method of identifying a subject who is likely to favorably respond to a bacterial composition provided herein, wherein the method comprises determining the expression of a biomarker in a biological sample obtained from the subject, wherein the subject is identified as likely to favorably respond to the bacterial composition if the expression of the biomarker is altered (increased or decreased) as compared to a reference subject (e.g., corresponding subject who does not favorably respond to the bacterial composition), and wherein the biomarker comprises one or more of the markers listed in Table 1. In some aspects, the biomarker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of the biomarker is altered (increased or decreased) by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of the biomarker is altered (increased or decreased) by at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 10- fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 30- fold, at least about 35-fold, at least about 40-fold, at least about 45-fold, or at least about 50-fold as compared to the reference subject.
[0114] In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of fecal albumin in the subject is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of elafin is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of Reg3a is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of CXCL10 is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of IL-6 is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of IL-8 is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of TNF-a is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of Hs-CRP is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of IFN-y is altered (decreased or increased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of IL2Ra is altered (increased or decreased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of IL-7 is altered (increased or decreased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of IL-15 is altered (increased or decreased) as compared to the reference subject. In some aspects, a subject is likely to favorably respond to a bacterial composition if the expression of IL-10 is altered (increased or decreased) as compared to the reference subject.
[0115] In some aspects, where a subject is identified as likely to favorably respond to a bacterial composition, one or more additional doses of the bacterial composition is administered to the subject.
[0116] For any of the methods provided herein where a bacterial composition is administered to a subject, in some aspects, the subject receives a pretreatment protocol priorto the administration of the bacterial composition. In some aspects, a pretreatment protocol prepares the gastrointestinal tract of the subject for administration of the bacterial composition. In some aspects, the pretreatment protocol comprises an antibiotic treatment (e.g, vancomycin). In some aspects, the pretreatment protocol comprises a colonic cleansing (e.g, enema), wherein the colonic cleansing substantially empties the contents of the patient's colon. As used herein, "substantially emptying the contents of the colon" refers to removal of at least about 75%, at least about 80%, at least about 90%, at least about 95%, or about 100% of the contents of the ordinary volume of colon contents. In some aspects, the subject receives multiple pretreatment protocols (e.g., an antibiotic treatment preceding a colon-cleansing protocol) prior to the administration of a bacterial composition.
[0117] In some aspects, a subject does not receive a pretreatment protocol prior to the administration of a bacterial composition. Instead, in some aspects, a bacterial composition is administered to reduce, alleviate, or prevent intestinal dysbiosis associated with subsequent treatment of the subject for a disease or disorder requiring treatment (e.g., allogeneic or autologous HSCT). In some aspects, a subject receives a pretreatment protocol prior to administration of a bacterial composition (such as that described herein) and the subject receives subsequent treatment for a disease or disorder requiring treatment (e.g., allogeneic or autologous HSCT) following administration of the bacterial composition.
[0118] In some aspects, a pretreatment protocol is administered to a subject at least about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, or about 15 days prior to the administration of a bacterial composition. In some aspects, subsequent treatment of the subject for a disease or disorder requiring treatment (e.g., allogeneic or autologous HSCT) occurs at least about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, or about 15 days after administration of a bacterial composition.
[0119] Where a bacterial composition is administered to a subject, the bacterial composition can be administered via any suitable route of administration. In some aspects, a bacterial composition is administered enterically (by a route of access to the gastrointestinal tract). For instance, in some aspects, a bacterial composition is administered to the subject via oral administration, rectal administration (including enema,suppository, or colonoscopy), by an oral or nasal tube (nasogastric, nasojejunal, oral gastric, or oral jejunal). In some aspects, a bacterial composition is administered to the subject orally.
[0120] In some aspects, a bacterial composition is administered to at least one region of the gastrointestinal tract, including the mouth, esophagus, stomach, small intestine, large intestine, and rectum. In some aspects, a bacterial composition is administered to all regions of the gastrointestinal tract. In some aspects, a bacterial composition is administered orally in the form of medicaments such as powders, capsules, tablets, gels or liquids. The bacterial composition can also be administered in a gel or liquid form by the oral route or through a nasogastric tube, or by the rectal route in a gel or liquid form, by enema or instillation through a colonoscope or by a suppository.
[0121] In some aspects, a bacterial composition provided herein is administered with other agents (e.g., anti-microbial agents or prebiotics) as a combination therapy mode. Additional examples of other agents include chemotherapy drugs, small molecule drugs or antibodies that stimulate the immune response to a given cancer. In some aspects, other agents can include an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody, an anti-PD-Ll antibody, or an anti-CTLA-4 antibody. Non-limiting examples of other antibodies that can be used in combination with the designed compositions of the present disclosure include an anti-OX40 (also known as CD 134, TNFRSF4, ACT35 and / or TXGP1L) antibody, an anti-CD137 antibody, an anti-LAG-3 antibody, or an anti-GITR antibody. In some aspects, a bacterial composition is administered without other agents (e.g., anti -microbial agents or prebiotics).
[0122] In some aspects, a bacterial composition is administered before HSCT (e.g., allo- HSCT), after HSCT, or after administration of, e.g., anti-bacterial agents, following HSCT, and combinations thereof. In some aspects, a bacterial composition as described herein is administered before HSCT, after HSCT, and after administration of, e.g., anti-bacterial agents, following HSCT
[0123] In some aspects, a bacterial composition is included in combination therapy with one or more anti-microbial agents, which include anti-bacterial agents, anti-fungal agents, anti-viral agents and anti-parasitic agents.
[0124] Anti-bacterial agents include cephalosporin antibiotics (cephalexin, cefuroxime, cefadroxil, cefazolin, cephalothin, cefaclor, cefamandole, cefoxitin, cefprozil, andceftobiprole); fluoroquinolone antibiotics (cipro, Levaquin, floxin, tequin, avelox, and norflox); tetracycline antibiotics (tetracycline, minocycline, oxytetracycline, and doxycycline); penicillin antibiotics (amoxicillin, ampicillin, penicillin V, dicloxacillin, carbenicillin, vancomycin, and methicillin); and carbapenem antibiotics (ertapenem, doripenem, imipenem / cilastatin, and meropenem). In some aspects, the anti-bacterial agent is vancomycin.
[0125] Anti-viral agents include Abacavir, Acyclovir, Adefovir, Amprenavir, Atazanavir, Cidofovir, Darunavir, Delavirdine, Didanosine, Docosanol, Efavirenz, Elvitegravir, Emtricitabine, Enfuvirtide, Etravirine, Famciclovir, Foscarnet, Fomivirsen, Ganciclovir, Indinavir, Idoxuridine, Lamivudine, Lopinavir Maraviroc, MK-2048, Nelfinavir, Nevirapine, Penciclovir, Raltegravir, Rilpivirine, Ritonavir, Saquinavir, Stavudine, Tenofovir Trifluridine, Valaciclovir, Valganciclovir, Vidarabine, Ibacitabine, Amantadine, Oseltamivir, Rimantidine, Tipranavir, Zalcitabine, Zanamivir and Zidovudine.
[0126] Examples of antifungal compounds include, but are not limited to polyene antifungals such as natamycin, rimocidin, filipin, nystatin, amphotericin B, candicin, and hamycin; imidazole antifungals such as miconazole, ketoconazole, clotrimazole, econazole, omoconazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, sulconazole, and tioconazole; triazole antifungals such as fluconazole, itraconazole, isavuconazole, ravuconazole, posaconazole, voriconazole, terconazole, and albaconazole; thiazole antifungals such as abafungin; allylamine antifungals such as terbinafine, naftifine, and butenafine; and echinocandin antifungals such as anidulafungin, caspofungin, and micafungin. Other compounds that have antifungal properties include, but are not limited to polygodial, benzoic acid, ciclopirox, tolnaftate, undecylenic acid, flucytosine or 5 -fluorocytosine, griseofulvin, and haloprogin.
[0127] In some aspects, a bacterial composition is included in combination therapy with one or more corticosteroids, mesalazine, mesalamine, sulfasalazine, sulfasalazine derivatives, immunosuppressive drugs, cyclosporin A, mercaptopurine, azathiopurine, prednisone, methotrexate, antihistamines, glucocorticoids, epinephrine, theophylline, cromolyn sodium, anti-leukotrienes, anti-cholinergic drugs for rhinitis, anti-cholinergic decongestants, mast-cell stabilizers, monoclonal anti-IgE antibodies, vaccines, and combinations thereof.IV. Bacterial Compositions
[0128] As described above, one or more of the methods provided herein comprise administering a bacterial composition to a subject. In some aspects, bacterial compositions useful for the present disclosure have been specifically designed to comprise one or more bacterial species that exhibit certain functional features that are useful for the methods provided herein (e.g., treating a disease or condition described herein, e.g., bloodstream infection and / or gastrointestinal disease or condition). Such bacterial compositions can include material directly derived from feces of healthy humans or such compositions can include material fermented from bacterial cultures, including a biologically pure culture. In some aspects, a bacterial composition can comprise both material directly derived from feces of healthy humans and material fermented from bacterial cultures. In addition to the disclosures provided herein, additional examples of bacterial compositions (including useful bacterial species) that can be used with the methods provided herein are provided in U. S. Publ. No. 20210196766A1 and U. S. Publ. No. 20240000859A1, each of which is incorporated herein by reference in its entirety.
[0129] In some aspects, one or more bacteria described herein are known in the art to have alternative names. In some aspects, " Clostridium innocuum" is also referred to herein as "[Clostridium innocuum]" and / or "[Clostridium] innocuum." In some aspects, " Clostridium bolteae" is also referred to herein as "[Clostridium] bolteae" and / or " Enterocloster bolteae." In some aspects, " Eubacterium callanderi" is also referred to herein as " Eubacterium maltosivorans." In some aspects, " Blautiahominis" is also referred to herein as " Blautia coccoides group" and / or " Blautia celeris." In some aspects, " [Faecalicatena] contorta group" is also referred to herein as " Faecalicatena conlorla." " Faecalicatena fissicalena" and / or " Faecalicatena orotica." In some aspects, " Erysipelatoclostridium ramosum" is also referred to herein as " Thomasclavelia ramosa." In some aspects, " Faecalicatena orotica" is also referred to herein as " [Faecalicatena] orotica." In some aspects, " Dorea longicatena" is also referred to herein as " Dorea amylophila." In some aspects, " Clostridium aldenense" is also referred to herein as " [Clostridium] aldenense group" and / or " Enterocloster aldenensis." In some aspects, " [Clostridium] symbiosum" is also referred to herein as " [Clostridium] symbiosum" and / or " Clostridium transplantifaecale. "
[0130] As described above, a bacterial composition that can be used with the methods provided herein comprise a plurality of bacterial species that exhibit one or more of the following features: (1) capable of engrafting (long-term and / or transient) when administered to a subject, (2) capable of having anti-inflammatory activity in epithelial cells (e.g., inhibiting TNF-a-driven IL-8 secretion in epithelial cells in vitro, ability to down- modulate expression of inflammatory genes (e.g., CXCL1, CXCL2, CXCL3, CXCL11, ICAM1)), (3) not capable of inducing pro-inflammatory activity, (4) capable of producing a secondary bile acid (e.g., 7a-dehydroxylase and bile salt hydrolase activity), (5) capable of producing a tryptophan metabolite (e.g., indole, 3-methyl indole, indolepropionic acid), (6) capable of restoring epithelial integrity as determined by a primary epithelial cell monolayer barrier integrity assay, (7) capable of being associated with reduction of risk of infection or GvHD following HSCT, (8) capable of not being associated with clinical nonremission of infection or GvHD following HSCT, (9) capable of producing a short-chain fatty acid (e.g., butyrate, propionate), (10) capable of inhibiting a HDAC activity, (11) capable of producing a medium-chain fatty acid (e.g., valerate, hexanoate), (12) capable of expressing catalase activity, (13) capable of having alpha-fucosidase activity, (14) capable of inducing Wnt activation, (15) capable of producing a B vitamin (e.g., thiamin (Bl) and / or pyridoxamine (B6)), (16) capable of reducing fecal calprotectin level, (17) not capable of activating a toll-like receptor pathway (e.g., TLR4 or TLR5), (18) capable of activating a toll-like receptor pathway (e.g., TLR2), (19) capable of restoring colonization resistance, (20) capable of a broad range of carbon source utilization; (21) capable of reducing VRE pathogen carriage, (22) capable of reducing CRE pathogen carriage, (23) capable of coadministration with a carrier or excipient described herein, without substantially decreasing the therapeutic benefit of the administered species, (24) capable of being associated with the healthy human gut microbiota, (25) capable of not being associated with toxin and hemolysin genes associated with Clostridial pathogens and no significant cytopathic effects in vitro, (26) susceptible to multiple clinically relevant antibiotics, (27) capable of not being associated with genes that are both likely responsible for the observed antibiotic resistances and transmissible, (28) capable of inhibiting epithelial cell apoptosis, (29) capable of down-modulating one or more genes induced in IFN-y treated colonic organoids (e.g., those associated with inflammatory chemokine signaling, NF-KB signaling, TNF family signaling, type I interferon signaling, type II interferon signaling, TLRsignaling, lymphocyte trafficking, Thl7 cell differentiation, Th2 differentiation, apoptosis, inflammasomes, autophagy, oxidative stress, MHC class I and II antigen presentation, complement, mTor, nod-like receptor signaling, PI3K signaling, or combinations thereof), (30) capable of reducing the expression of one or more inhibitory receptors (e.g., TIGIT, TIM-3, or LAG-3) on CD8+ T cells, (31) capable of increasing expression of one or more genes / proteins associated with CD8+ T cell activation and / or function (e.g., CD45RO, CD69, IL-24, TNF-a, perforin, or IFN-y), (32) capable of enhancing the ability of CD8+ T cells to kill tumor cells, (33) capable of enhancing the efficacy of an immune checkpoint inhibitor therapy, (34) capable of promoting the recruitment of CD8+ T cells to tumors, (35) capable of inducing an anti-inflammatory IL-10-skewed IL-10 / IL-6 cytokine ratio in macrophages, (36) capable of inducing less inflammatory responses but similar pathogen defense responses in macrophages than a donor-derived spore-based composition, (37) capable of increasing the amount of anti-inflammatory mediators in (e.g., IL-1 receptor antagonists (IL-IRA), IL-4, IL-6, IL-10, IL-11, IL-13, TGF-P), (38) capable of reducing colonic inflammation, (39) capable of treating and / or preventing a disease or disorder, such as those associated with dysbiosis of a gastrointestinal tract, (40) capable of increasing the diversity of the gastrointestinal microbiome in a subject, (41) capable of improving mucosal and / or epithelial barrier integrity in a subject compared to a reference control (e.g., untreated patients or the subject prior to treatment), (42) capable of promoting mucosal healing, (43) capable of reducing incidence of infection, (44) capable of reducing the need for antibiotics in a subject, (45) capable of increasing the probability of survival in a subject, (46) capable of reducing the risk of relapse of primary cancer, (47) capable of reducing the abundance of a biomarker of infection in the stool of a subject, (48) capable of increasing the abundance of a biomarker of an administered species in the stool of a subject, (49) capable of targeted delivery of most (e.g., 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% of the administered species relative to the number of colony forming units administered) or all of the administered species to the intestines of the subject (e.g., through encapsulation, or through coating one or more components of a dosage form with an enteric polymer), (50) capable of a therapeutic benefit following a single administration of a composition or pharmaceutical composition described herein to a subject, (51) capable of coadministration with an additional agent described herein, without substantially decreasing the therapeutic benefit of theadministered species, (52) capable of increasing the Treg: Thl orTreg: Thl7 ratios on the lamina propria of mice, (53) capable of altering the expression of one or more biomarkers listed in Table 1, (54) or any combination thereof. Non-limiting examples of designed compositions are described, e.g., in FIG. 9.
[0131] In some aspects, abacterial composition disclosed herein comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, or all of the features provided above. In some aspects, a bacterial composition useful for the present disclosure comprises features that target multiple biological pathways, such that the same composition can be used to treat a wide range of diseases and disorders.
[0132] In some aspects, a bacterial composition disclosed herein comprises selected families, genera, or species of bacteria. In general, the bacteria are commensal bacteria initially derived from, for example, a GI tract, typically the GI tract of a human, isolated and grown into pure cultures that can be used in designing a bacterial composition useful for the present disclosure. These bacteria are selected for desired properties as described herein. Unless indicated otherwise, a bacterial composition provided herein comprises a plurality of bacteria. Accordingly, in some aspects, a bacterial composition disclosure comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21, 22, 23, 24, 25, 26, 27, 28, 29 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or at least 40, at least 50, or greater than about 50 types of bacteria, as defined by species or operational taxonomic unit (OTU), or otherwise as provided herein. The bacteria in a composition may be present in approximately equal amounts of viable bacteria or each family, genus, species of OTU. In some aspects, the bacteria are present in varying amounts in the composition. Non-limiting examples of bacterial species that can be used in designing the microbiome compositions disclosed herein are provided in FIG. 9.
[0133] In some aspects, a bacterial composition useful for the present disclosure comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DEI." In some aspects, a bacterial composition useful for the present disclosure comprises the DEI composition. In someaspects, a bacterial composition consists essentially of the DEI composition. In some aspects, a bacterial composition consists of the DEI composition. In some aspects, a bacterial composition useful for the present disclosure comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, or all of the bacterial species present in the composition referred to herein as " DE2." In some aspects, a bacterial composition comprises the DE2 composition. In some aspects, a bacterial composition consists essentially of the DE2 composition. In some aspects, a bacterial composition consists of the DE2 composition. In some aspects, a bacterial composition one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, or all of the bacterial species present in the composition referred to herein as " DE3." In some aspects, a bacterial composition comprises the DE3 composition. In some aspects, a bacterial composition consists essentially of the DE3 composition. In some aspects, a bacterial composition consists of the DE3 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, or all of the bacterial species present in the composition referred to herein as " DE4." In some aspects, a bacterial composition comprises the DE4 composition. In some aspects, a bacterial composition consists essentially of the DE4 composition. In some aspects, a bacterial composition consists of the DE4 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE5." In some aspects, a bacterial composition comprises the DE5 compsoition. In some aspects, a bacterial composition consists essentially of the DE5 composition. In some aspects, a bacterial composition consists of the DE5 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, or all of the bacterial species present in the composition referred to herein as " DE6." In some aspects, a bacterial composition comprises the DE6 composition. In some aspects, a bacterial composition consists essentially of the DE6 composition. In some aspects, a bacterial composition consists of the DE6 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE7." In some aspects, a bacterial composition comprises the DE7 composition. In some aspects, a bacterial composition consists essentially of the DE7 composition. In some aspects, a bacterial compositionconsists of the DE7 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, or all of the bacterial species present in the composition referred to herein as " DE8." In some aspects, a bacterial composition comprises the DE8 composition. In some aspects, a bacterial composition consists essentially of the DE8 composition. In some aspects, a bacterial composition consists of the DE8 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, or all of the bacterial species present in the composition referred to herein as " DE9." In some aspects, a bacterial composition comprises the DE9 composition. In some aspects, a bacterial composition consists essentially of the DE9 composition. In some aspects, a bacterial composition consists of the DE9 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, or all of the bacterial species present in the composition referred to herein as " DE10. " In some aspects, a bacterial composition comprises the DE10 composition. In some aspects, a bacterial composition consists essentially of the DE10 composition. In some aspects, a bacterial composition consists of the DE10 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, or all of the bacterial species present in the composition referred to herein as " DE 11." In some aspects, abacterial composition comprises the DE11 composition. In some aspects, a bacterial composition consists essentially of the DE11 composition. In some aspects, a bacterial composition consists of the DEI 1 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, or all of the bacterial species present in the composition referred to herein as " DE12." In some aspects, a bacterial composition comprises the DE12 composition. In some aspects, a bacterial composition consists essentially of the DE12 composition. In some aspects, a bacterial composition consists of the DE12 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE13." In some aspects, a bacterial composition comprises the DE13 composition. In some aspects, a bacterial composition consists essentially of the DEI 3 composition. In some aspects, a bacterial composition consists of the DEI 3 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of thebacterial species present in the composition referred to herein as " DE14." In some aspects, a bacterial composition comprises the DE14 composition. In some aspects, a bacterial composition consists essentially of the DE14 composition. In some aspects, a bacterial composition consists of the DEM composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE15." In some aspects, a bacterial composition comprises the DEI 5 composition. In some aspects, a bacterial composition consists essentially of the DEI 5 composition. In some aspects, a bacterial composition consists of the DEI 5 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, or all of the bacterial species present in the composition referred to herein as " DE16." In some aspects, a bacterial composition comprises the DE16 composition. In some aspects, a bacterial composition consists essentially of the DE16 composition. In some aspects, a bacterial composition consists of the DE16 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, or all of the bacterial species present in the composition referred to herein as " DE17. " In some aspects, a bacterial composition comprises the DE17 composition. In some aspects, a bacterial composition consists essentially of the DE17 composition. In some aspects, a bacterial composition consists of the DE17 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, or all of the bacterial species present in the composition referred to herein as " DE18." In some aspects, a bacterial composition comprises the DEI 8 composition. In some aspects, a bacterial composition consists essentially of the DEI 8 composition. In some aspects, a bacterial composition consists of the DEI 8 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, or all of the bacterial species present in the composition referred to herein as " DE19. " In some aspects, a bacterial composition comprises the DE19 composition. In some aspects, a bacterial composition consists essentially of the DE19 composition. In some aspects, a bacterial composition consists of the DE19 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, or all of the bacterial species present in the composition referred to herein as " DE20." In some aspects, a bacterial composition comprises the DE20 composition. In some aspects, a bacterialcomposition consists essentially of the DE20 composition. In some aspects, a bacterial composition consists of the DE20 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, or all of the bacterial species present in the composition referred to herein as " DE21." In some aspects, a bacterial composition comprises the DE21 composition. In some aspects, a bacterial composition consists essentially of the DE21 composition. In some aspects, a bacterial composition consists of the DE21 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, or all of the bacterial species present in the composition referred to herein as " DE22." In some aspects, a bacterial composition comprises the DE22 composition. In some aspects, a bacterial composition consists essentially of the DE22 composition. In some aspects, a bacterial composition consists of the DE22 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, or all of the bacterial species present in the composition referred to herein as " DE23." In some aspects, a bacterial composition comprises the DE23 composition. In some aspects, a bacterial composition consists essentially of the DE23 composition. In some aspects, a bacterial composition consists of the DE23 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, or all of the bacterial species present in the composition referred to herein as " DE24." In some aspects, a bacterial composition comprises the DE24 composition. In some aspects, a bacterial composition consists essentially of the DE24 composition. In some aspects, a bacterial composition consists of the DE24 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, or all of the bacterial species present in the composition referred to herein as " DE25." In some aspects, a bacterial composition comprises the DE25 composition. In some aspects, a bacterial composition consists essentially of the DE25 composition. In some aspects, a bacterial composition consists of the DE25 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, or all of the bacterial species present in the composition referred to herein as " DE26." In some aspects, a bacterial composition comprises the DE26 composition. In some aspects, a bacterial composition consists essentially of the DE26 composition. In some aspects, a bacterial composition consists of the DE26 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven,eight, nine, 10, or all of the bacterial species present in the composition referred to herein as " DE27." In some aspects, a bacterial composition comprises the DE27 composition. In some aspects, a bacterial composition consists essentially of the DE27 composition. In some aspects, a bacterial composition consists of the DE27 composition. In some aspects, abacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, or all of the bacterial species present in the composition referred to herein as " DE28." In some aspects, a bacterial composition comprises the DE28 composition. In some aspects, a bacterial composition consists essentially of the DE28 composition. In some aspects, a bacterial composition consists of the DE28 composition. In some aspects, abacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE29." In some aspects, a bacterial composition comprises the DE29 composition. In some aspects, a bacterial composition consists essentially of the DE29 composition. In some aspects, a bacterial composition consists of the DE29 composition. In some aspects, abacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE30." In some aspects, a bacterial composition comprises the DE30 composition. In some aspects, a bacterial composition consists essentially of the DE30 composition. In some aspects, a bacterial composition consists of the DE30 composition. In some aspects, abacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE31." In some aspects, a bacterial composition comprises the DE31 composition. In some aspects, a bacterial composition consists essentially of the DE31 composition. In some aspects, a bacterial composition consists of the DE31 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, or all of the bacterial species present in the composition referred to herein as " DE32." In some aspects, a bacterial composition comprises the DE32 composition. In some aspects, a bacterial composition consists essentially of the DE32 composition. In some aspects, a bacterial composition consists of the DE32 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE33." In some aspects, a bacterial composition comprises the DE33 composition. In some aspects,a bacterial composition consists essentially of the DE33 composition. In some aspects, a bacterial composition consists of the DE33 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE34." In some aspects, a bacterial composition comprises the DE34 composition. In some aspects, a bacterial composition consists essentially of the DE34 composition. In some aspects, a bacterial composition consists of the DE34 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE35." In some aspects, a bacterial composition comprises the DE35 composition. In some aspects, a bacterial composition consists essentially of the DE35 composition. In some aspects, a bacterial composition consists of the DE35 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE36." In some aspects, a bacterial composition comprises the DE36 composition. In some aspects, a bacterial composition consists essentially of the DE36 composition. In some aspects, a bacterial composition consists of the DE36 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, or all of the bacterial species present in the composition referred to herein as " DE37." In some aspects, a bacterial composition comprises the DE37 composition. In some aspects, a bacterial composition consists essentially of the DE37 composition. In some aspects, a bacterial composition consists of the DE37 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, or all of the bacterial species present in the composition referred to herein as " DE38." In some aspects, a bacterial composition comprises the DE38 composition. In some aspects, a bacterial composition consists essentially of the DE38 composition. In some aspects, a bacterial composition consists of the DE38 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE39." In some aspects, a bacterial composition comprises the DE39 composition. In some aspects, a bacterial composition consists essentially of the DE39 composition. In some aspects, a bacterial composition consists of the DE39 composition. In some aspects, a bacterialcomposition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE40." In some aspects, a bacterial composition comprises the DE40 composition. In some aspects, a bacterial composition consists essentially of the DE40 composition. In some aspects, a bacterial composition consists of the DE40 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE41." In some aspects, a bacterial composition comprises the DE41 composition. In some aspects, a bacterial composition consists essentially of the DE41 composition. In some aspects, a bacterial composition consists of the DE41 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE42." In some aspects, a bacterial composition comprises the DE42 composition. In some aspects, a bacterial composition consists essentially of the DE42 composition. In some aspects, a bacterial composition consists of the DE42 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, or all of the bacterial species present in the composition referred to herein as " DE43." In some aspects, a bacterial composition comprises the DE43 composition. In some aspects, a bacterial composition consists essentially of the DE43 composition. In some aspects, a bacterial composition consists of the DE43 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, or all of the bacterial species present in the composition referred to herein as " DE44." In some aspects, a bacterial composition comprises the DE44 composition. In some aspects, a bacterial composition consists essentially of the DE44 composition. In some aspects, a bacterial composition consists of the DE44 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE45." In some aspects, a bacterial composition comprises the DE45 composition. In some aspects, a bacterial composition consists essentially of the DE45 composition. In some aspects, a bacterial composition consists of the DE45 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, or all of the bacterial species present in the composition referred to herein as " DE46."In some aspects, a bacterial composition comprises the DE46 composition. In some aspects, a bacterial composition consists essentially of the DE46 composition. In some aspects, a bacterial composition consists of the DE46 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, or all of the bacterial species present in the composition referred to herein as " DE47." In some aspects, a bacterial composition comprises the DE47 composition. In some aspects, a bacterial composition consists essentially of the DE47 composition. In some aspects, a bacterial composition consists of the DE47 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE48." In some aspects, a bacterial composition comprises the DE48 composition. In some aspects, a bacterial composition consists essentially of the DE48 composition. In some aspects, a bacterial composition consists of the DE48 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE49." In some aspects, a bacterial composition comprises the DE49 composition. In some aspects, a bacterial composition consists essentially of the DE49 composition. In some aspects, a bacterial composition consists of the DE49 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE50." In some aspects, a bacterial composition comprises the DE50 composition. In some aspects, a bacterial composition consists essentially of the DE50 composition. In some aspects, a bacterial composition consists of the DE50 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE51." In some aspects, a bacterial composition comprises the DE51 composition. In some aspects, a bacterial composition consists essentially of the DE51 composition. In some aspects, a bacterial composition consists of the DE51 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, or all of the bacterial species present in the composition referred to herein as " DE52." In some aspects, a bacterial composition comprises the DE52 composition. In some aspects, a bacterial composition consists essentially of the DE52 composition. In some aspects, a bacterial composition consists ofthe DE33 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, or all of the bacterial species present in the composition referred to herein as " DE53." In some aspects, a bacterial composition comprises the DE53 composition. In some aspects, a bacterial composition consists essentially of the DE53 composition. In some aspects, a bacterial composition consists of the DE53 composition. In some aspects, a bacterial composition comprises one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, or all of the bacterial species present in the composition referred to herein as " DE54." In some aspects, a bacterial composition comprises the DE54 composition. In some aspects, a bacterial composition consists essentially of the DE54 composition. In some aspects, a bacterial composition consists of the DE54 composition.
[0134] In some aspects, a bacterial composition disclosed herein comprises one or more bacteria from the family Ruminococcaceae, Lachnospiraceae, Sutterellaceae, Clostridiaceae, Erysipelotrichaceae, Bacteroidaceae, Akkermansiaceae. Peptostreptococcaceae, Eubacteriaceae, Clostridiales Family XIII, or Desulfovibrionaceae. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, or all of the families listed.
[0135] In some aspects, a bacterial composition comprises bacteria having at least about 97%, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99%, identity to a 16S rDNA sequence (e.g., a full length or variable region of a 16S DNA sequence) to one or more of the following bacterial species: Eubacterium maltosivorans, Clostridium aldenense, Clostridium bolteae, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium symbiosum, Eubacterium rectale, Ruminococcus gnavus, Ruminococcus torques, Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lachnospiraceae bacterium 5_1_57FAA, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris,Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium butyricum, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, Clostridium disporicum, Clostridium subterminale, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, or Ruminococcus lactaris. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-five, thirty, thirty-five, forty, forty-five, fifty, or all of the species listed.
[0136] In some aspects, a bacterial composition comprises bacteria having at least about 97%, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99%, identity to a 16S rDNA sequence (e.g., a full length or variable region of a 16S DNA sequence) to one or more of the following bacterial species: Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes onderdonkii, Alistipes putredinis, Alistipes senegalensis, Alistipes shahii, Alistipes timonensis, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Atlantibacter hermannii, Atlantibacter subterranea, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides eggerthii, Bacteroides faecichinchillae, Bacteroides faecis, Bacteroides finegoldii, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides oleiciplenus, Bacteroides ovatus, Bacteroides rodentium, Bacteroides salyersiae, Bacteroidesstercorirosoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium faecale, Bifidobacterium kashiwanohense, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium ruminantium, Bifidobacterium stercoris, Blautia coccoides, Blautia hansenii, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Brenneria alni, Butyricimonas faecihominis, Cedecea lapagei, Cellulosilyticum lentocellum, Citrobacter amalonaticus, Citrobacter farmeri, Citrobacter koseri, Citrobacter sedlakii, Citrobacter youngae, Clostridium aldenense, Clostridium asparagiforme, Clostridium beijerinckii, Clostridium bolteae, Clostridium butyricum, Clostridium carnis, Clostridium celatum, Clostridium chauvoei, Clostridium chromiireducens, Clostridium citroniae, Clostridium clostridioforme, Clostridium cocleatum, Clostridium dakarense, Clostridium diolis, Clostridium disporicum, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium paraputrificum, Clostridium puniceum, Clostridium quinii, Clostridium saccharobutylicum, Clostridium saccharoperbutylacetonicum, Clostridium sartagoforme, Clostridium saudiense, Clostridium scindens, Clostridium septicum, Clostridium spiroforme, Clostridium subterminale, Clostridium sulfidigenes, Clostridium symbiosum, Clostridium tertium, Clostridium thiosulfatireducens, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Cronobacter condimenti, Cronobacter muytjensii, Cronobacter sakazakii, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Enterobacter asburiae, Enterobacter bugandensis, Enterobacter cloacae, Enterobacter hormaechei, Enterobacter tabaci, Erysipelatoclostridium ramosum, Escherichia albertii, Escherichia coli, Escherichia fergusonii, Escherichia marmotae, Eubacterium callanderi, Eubacterium limosum, Eubacterium maltosivorans, Eubacterium rectale, Eubacterium tenue, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinibacter bartlettii, Intestinimonas butyriciproducens, Kosakonia cowanii, Kosakonia oryzendophytica, Kosakonia oryziphila, Kosakonia pseudosacchari, Kosakonia sacchari,Lachnoclostridium pacaense, Lachnospira pectinoschiza, Lactobacillus fermentum, Lactobacillus gorillae, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Metakosakonia massiliensis, Mixta theicola, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium ghonii, Paeniclostridium sordellii, Pantoea beijingensis, Parabacteroides distasonis, Parabacteroides johnsonii, Parabacteroides merdae, Paraclostridium benzoelyticum, Paraclostridium bifermentans, Pectobacterium carotovorum, Peptostreptococcus anaerobius, Peptostreptococcus stomatis, Phytobacter ursingii, Pseudescherichia vulneris, Pseudocitrobacter anthropi, Pseudocitrobacter faecalis, Pseudoflavonifractor capillosus, Pseudoflavonifractor phocaeensis, Raoultella planticola, Robinsoniella peoriensis, Romboutsia ilealis, Romboutsia lituseburensis, Romboutsia sedimentorum, Romboutsia timonensis, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Salmonella bongori, Salmonella enterica, Sellimonas intestinalis, Shigella boydii, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Subdoligranulum variabile, Terrisporobacter glycolicus, Terrisporobacter mayombei, Terrisporobacter petrolearius, Trabulsiella odontotermitis, Turicibacter sanguinis, Tyzzerella nexilis, or Yokenella regensburgei. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty -five, thirty, thirty-five, forty, forty-five, fifty, or all of the species listed.
[0137] In some aspects, a bacterial composition comprises bacteria having at least about 97%, e.g., at least 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99%, identity to a 16S rDNA sequence (e.g., a full length or variable region of a 16S DNA sequence) to one or more of the following bacterial species: Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia marasmi,Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium asparagiforme, Clostridium bolteae, Clostridium butyricum, Clostridium citroniae, Clostridium clostridioforme, Clostridium cocleatum, Clostridium disporicum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium subterminale, Clostridium symbiosum, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Eubacterium maltosivorans, Eubacterium rectale, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnoclostridium pacaense, Lactobacillus fermentum, Lactonifactor longoviformis, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Pseudoflavonifractor capillosus, Pseudoflavonifractor phocaeensis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Terrisporobacter mayombei, Terrisporobacter petrolearius, or Turicibacter sanguinis. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-five, thirty, thirty-five, forty, forty-five, fifty, or all of the species listed.
[0138] In some aspects, a bacterial composition comprises bacteria having at least about 97%, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99%, identity to a 16S rDNA sequence (e.g., a full length or variable region of a 16S DNA sequence) to one or more of the following bacterial species: Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes onderdonkii, Alistipes putredinis, Alistipes senegalensis, Alistipes shahii, Alistipes timonensis, Anaerofustisstercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides eggerthii, Bacteroides faecichinchillae, Bacteroides faecis, Bacteroides finegoldii, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides oleiciplenus, Bacteroides ovatus, Bacteroides rodentium, Bacteroides salyersiae, Bacteroides stercorirosoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium faecale, Bifidobacterium kashiwanohense, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium ruminantium, Bifidobacterium stercoris, Blautia coccoides, Blautia hansenii, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium asparagiforme, Clostridium beijerinckii, Clostridium bolteae, Clostridium butyricum, Clostridium carnis, Clostridium celatum, Clostridium chauvoei, Clostridium chromiireducens, Clostridium citroniae, Clostridium clostridioforme, Clostridium cocleatum, Clostridium dakarense, Clostridium diolis, Clostridium disporicum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium paraputrificum, Clostridium puniceum, Clostridium quinii, Clostridium saccharobutylicum, Clostridium saccharoperbutylacetonicum, Clostridium sartagoforme, Clostridium saudiense, Clostridium scindens, Clostridium septicum, Clostridium spiroforme, Clostridium subterminale, Clostridium sulfidigenes, Clostridium symbiosum, Clostridium tertium, Clostridium thiosulfatireducens, Collinsella aerofaciens, Coprococcus comes, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Eubacterium maltosivorans, Eubacterium rectale, Eubacterium tenue, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinibacter bartlettii, Intestinimonas butyriciproducens, Lachnoclostridium pacaense, Lactobacillus fermentum, Lactobacillus gorillae, Lactonifactor longoviformis, Longicatena caecimuris, Murimonas intestini,Oscillibacter ruminantium, Paeniclostridium ghonii, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides johnsonii, Parabacteroides merdae, Paraclostridium benzoelyticum, Paraclostridium bifermentans, Peptostreptococcus anaerobius, Peptostreptococcus stomatis, Pseudoflavonifractor capillosus, Pseudoflavonifractor phocaeensis, Robinsoniella peoriensis, Romboutsia ilealis, Romboutsia lituseburensis, Romboutsia sedimentorum, Romboutsia timonensis, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Subdoligranulum variabile, Terrisporobacter glycolicus, Terrisporobacter mayombei, Terrisporobacter petrolearius, or Turicibacter sanguinis. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-five, thirty, thirty-five, forty, forty-five, fifty, or all of the species listed.
[0139] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Eubacterium maltosivorans, Clostridium aldenense, Clostridium bolteae, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium symbiosum, Eubacterium rectale, Ruminococcus gnavus, Ruminococcus torques, Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lachnospiraceae bacterium 5_1_57FAA, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum,-Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium butyricum, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, Clostridium disporicum, Clostridium subterminale, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, or Ruminococcus lactaris. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-five, thirty, thirty-five, forty, forty- five, fifty, or all of the species listed.
[0140] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes onderdonkii, Alistipes putredinis, Alistipes senegalensis, Alistipes shahii, Alistipes timonensis, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Atlantibacter hermannii, Atlantibacter subterranea, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides eggerthii, Bacteroides faecichinchillae, Bacteroides faecis, Bacteroides finegoldii, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides oleiciplenus, Bacteroides ovatus, Bacteroides rodentium, Bacteroides salyersiae, Bacteroides stercorirosoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium faecale, Bifidobacterium kashiwanohense, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium ruminantium, Bifidobacterium stercoris, Blautia coccoides, Blautia hansenii, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Brenneria alni, Butyricimonas faecihominis, Cedecealapagei, Cellulosilyticum lentocellum, Citrobacter amalonaticus, Citrobacter farmeri, Citrobacter koseri, Citrobacter sedlakii, Citrobacter youngae, Clostridium aldenense, Clostridium asparagiforme, Clostridium beijerinckii, Clostridium bolteae, Clostridium butyricum, Clostridium carnis, Clostridium celatum, Clostridium chauvoei, Clostridium chromiireducens, Clostridium citroniae, Clostridium clostridioforme, Clostridium cocleatum, Clostridium dakarense, Clostridium diolis, Clostridium disporicum, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium paraputrificum, Clostridium puniceum, Clostridium quinii, Clostridium saccharobutylicum, Clostridium saccharoperbutylacetonicum, Clostridium sartagoforme, Clostridium saudiense, Clostridium scindens, Clostridium septicum, Clostridium spiroforme, Clostridium subterminale, Clostridium sulfidigenes, Clostridium symbiosum, Clostridium tertium, Clostridium thiosulfatireducens, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Cronobacter condimenti, Cronobacter muytjensii, Cronobacter sakazakii, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Enterobacter asburiae, Enterobacter bugandensis, Enterobacter cloacae, Enterobacter hormaechei, Enterobacter tabaci, Erysipelatoclostridium ramosum, Escherichia albertii, Escherichia coli, Escherichia fergusonii, Escherichia marmotae, Eubacterium callanderi, Eubacterium limosum, Eubacterium maltosivorans, Eubacterium rectale, Eubacterium tenue, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinibacter bartlettii, Intestinimonas butyriciproducens, Kosakonia cowanii, Kosakonia oryzendophytica, Kosakonia oryziphila, Kosakonia pseudosacchari, Kosakonia sacchari, Lachnoclostridium pacaense, Lachnospira pectinoschiza, Lactobacillus fermentum, Lactobacillus gorillae, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Metakosakonia massiliensis, Mixta theicola, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium ghonii, Paeniclostridium sordellii, Pantoea beijingensis, Parabacteroides distasonis, Parabacteroides johnsonii, Parabacteroides merdae, Paraclostridium benzoelyticum, Paraclostridium bifermentans, Pectobacterium carotovorum, Peptostreptococcus anaerobius, Peptostreptococcus stomatis, Phytobacter ursingii, Pseudescherichia vulneris, Pseudocitrobacter anthropi, Pseudocitrobacterfaecalis, Pseudoflavonifractor capillosus, Pseudoflavonifractor phocaeensis, Raoultella planticola, Robinsoniella peoriensis, Romboutsia ilealis, Romboutsia lituseburensis, Romboutsia sedimentorum, Romboutsia timonensis, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Salmonella bongori, Salmonella enterica, Sellimonas intestinalis, Shigella boydii, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Subdoligranulum variabile, Terrisporobacter glycolicus, Terrisporobacter mayombei, Terrisporobacter petrolearius, Trabulsiella odontotermitis, Turicibacter sanguinis, Tyzzerella nexilis, or Yokenella regensburgei. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty -five, thirty, thirty-five, forty, forty-five, fifty, or all of the species listed.
[0141] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium asparagiforme, Clostridium bolteae, Clostridium butyricum, Clostridium citroniae, Clostridium clostridioforme, Clostridium cocleatum, Clostridium disporicum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium subterminale, Clostridium symbiosum, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Eubacterium maltosivorans, Eubacterium rectale, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena fissicatena,Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnoclostridium pacaense, Lactobacillus fermentum, Lactonifactor longoviformis, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Pseudoflavonifractor capillosus, Pseudoflavonifractor phocaeensis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Terrisporobacter mayombei, Terrisporobacter petrolearius, or Turicibacter sanguinis. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-five, thirty, thirty-five, forty, forty-five, fifty, or all of the species listed.
[0142] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes onderdonkii, Alistipes putredinis, Alistipes senegalensis, Alistipes shahii, Alistipes timonensis, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides eggerthii, Bacteroides faecichinchillae, Bacteroides faecis, Bacteroides finegoldii, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides oleiciplenus, Bacteroides ovatus, Bacteroides rodentium, Bacteroides salyersiae, Bacteroides stercorirosoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium faecale, Bifidobacterium kashiwanohense, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium ruminantium, Bifidobacterium stercoris, Blautia coccoides, Blautia hansenii, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium asparagiforme,Clostridium beijerinckii, Clostridium bolteae, Clostridium butyricum, Clostridium carnis, Clostridium celatum, Clostridium chauvoei, Clostridium chromiireducens, Clostridium citroniae, Clostridium clostridioforme, Clostridium cocleatum, Clostridium dakarense, Clostridium diolis, Clostridium disporicum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium paraputrificum, Clostridium puniceum, Clostridium quinii, Clostridium saccharobutylicum, Clostridium saccharoperbutylacetonicum, Clostridium sartagoforme, Clostridium saudiense, Clostridium scindens, Clostridium septicum, Clostridium spiroforme, Clostridium subterminale, Clostridium sulfidigenes, Clostridium symbiosum, Clostridium tertium, Clostridium thiosulfatireducens, Collinsella aerofaciens, Coprococcus comes, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Eubacterium maltosivorans, Eubacterium rectale, Eubacterium tenue, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinibacter bartlettii, Intestinimonas butyriciproducens, Lachnoclostridium pacaense, Lactobacillus fermentum, Lactobacillus gorillae, Lactonifactor longoviformis, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium ghonii, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides johnsonii, Parabacteroides merdae, Paraclostridium benzoelyticum, Paraclostridium bifermentans, Peptostreptococcus anaerobius, Peptostreptococcus stomatis, Pseudoflavonifractor capillosus, Pseudoflavonifractor phocaeensis, Robinsoniella peoriensis, Romboutsia ilealis, Romboutsia lituseburensis, Romboutsia sedimentorum, Romboutsia timonensis, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Subdoligranulum variabile, Terrisporobacter glycolicus, Terrisporobacter mayombei, Terrisporobacter petrolearius, or Turicibacter sanguinis. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-five, thirty, thirty-five, forty, forty-five, fifty, or all of the species listed.
[0143] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia producta, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Faecalicatena orotica, Erysipelatoclostridium ramosum, Eisenbergiella tayi, Emergencia timonensis, Eubacterium maltosivorans, Flavonifractor plautii, Murimonas intestini, Blautia obeum, Dorea longicatena, or Clostridium scindens. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0144] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia coccoides, Blautia hominis, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Murimonas intestini, or Pseudoflavonifractor phocaeensis. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0145] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia coccoides, Blautia hominis, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Clostridium scindens, Dorea longicatena, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacteriumlimosum, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Murimonas intestini, or Pseudoflavonifractor phocaeensis. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0146] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Bacteroides salyersiae, Bacteroides vulgatus, Bifidobacterium longum, Blautia obeum, Clostridium asparagiforme, Clostridium bolteae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Dorea longicatena, Emergencia timonensis, Faecalicatena orotica, Gemmiger formicilis, Intestinibacter bartlettii, Intestinimonas butyr iciproducens, Romboutsia ilealis, Romboutsia timonensis, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Ruminococcus faecis, Subdoligranulum variabile, Terrisporobacter glycolicus, Terrisporobacter mayombei, or Terrisporobacter petrolearius. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0147] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes onderdonkii, Alistipes putredinis, Alistipes senegalensis, Alistipes shahii, Alistipes timonensis, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides finegoldii, Bacteroides intestinalis, Bacteroides oleiciplenus, Bacteroides stercorirosoris, Bacteroides thetaiotaomicron, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium faecale, Bifidobacterium kashiwanohense, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium ruminantium, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia marasmi, Blautia producta, Blautia stercoris, Clostridium aldenense, Clostridium subterminale, Clostridium sulfidigenes,Clostridium thiosulfatireducens, Emergencia timonensis, Faecalibacterium prausnitzii, Intestinibacter bartlettii, Intestinimonas butyriciproducens, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Terrisporobacter glycolicus, Terrisporobacter mayombei, or Terrisporobacter petrolearius. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0148] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia coccoides, Blautia hominis, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Murimonas intestini, or Pseudoflavonifractor phocaeensis. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0149] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia hominis, Blautia luti, Blautia obeum, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Faecalicatena orotica, Flavonifractor plautii, or Murimonas intestini. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0150] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia hominis, Blautia obeum, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Clostridium scindens, Dorea longicatena, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Faecalicatena orotica, Flavonifractor plautii, o Murimonas intestini. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0151] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Bacteroides salyersiae, Bacteroides vulgatus, Bifidobacterium longum, Blautia obeum, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Dorea longicatena, Emergencia timonensis, Faecalicatena orotica, Gemmiger formicilis, Intestinimonas butyriciproducens, Roseburia intestinalis, Ruminococcus faecis, Terrisporobacter mayombei, or Terrisporobacter petrolearius. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0152] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides faecis, Bacteroides intestinalis, Bifidobacterium longum, Bifidobacterium stercoris, Blautia hominis, Clostridium aldenense, Clostridium subterminale, Emergencia timonensis, Faecalibacterium prausnitzii, Intestinimonas butyriciproducens, Roseburia intestinalis, Terrisporobacter mayombei, or Terrisporobacter petrolearius. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial compositioncan comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0153] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia hominis, Blautia obeum, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Faecalicatena orotica, Flavonifractor plautii, o Murimonas intestini. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0154] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia hominis, Blautia obeum, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Faecalicatena orotica, Flavonifractor plautii, or Murimonas intestini. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0155] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia coccoides, Blautia hominis, Blautia luti, Blautia marasmi, Blautia producta, Blautia stercoris, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Murimonas intestini, or Pseudoflavonifractor phocaeensis. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of theforegoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0156] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia coccoides, Blautia hominis, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Murimonas intestini, or Pseudoflavonifractor phocaeensis. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0157] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia coccoides, Blautia hominis, Blautia luti, Blautia marasmi, Blautia obeum, Blautia producta, Blautia stercoris, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella massiliensis, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium limosum, Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor plautii, Murimonas intestini, or Pseudoflavonifractor phocaeensis. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0158] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Agathobaculum desmolans, Anaerotruncus colihominis, Blautia hominis, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum,Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Faecalicatena orotica, Flavonifractor plautii, Murimonas intestini, Roseburia intestinalis, Terrisporobacter mayombei, or Terrisporobacter petrolearius. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0159] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia hominis, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Faecalicatena orotica, Flavonifractor plautii, o Murimonas intestini. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0160] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia hominis, Blautia obeum, Blautia wexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Faecalicatena orotica, Flavonifractor plautii, or Murimonas intestini. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0161] In some aspects, a bacterial composition comprises one or more of the following bacterial species: Anaerotruncus colihominis, Blautia hominis, Blautia obeum, Blautiawexlerae, Clostridium aldenense, Clostridium bolteae, Clostridium innocuum, Dorea longicatena, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Faecalicatena orotica, Flavonifractor plautii, or Murimonas intestini. In some aspects, one or more of the bacteria in a composition has at least about 97% identity, e.g., at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99% identity, to a 16S rDNA of the foregoing species. In some aspects, a bacterial composition can comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or all of the bacterial species listed.
[0162] In some aspects, a bacterial composition of the present disclosure comprises one or more bacteria comprising a 16S rDNA sequence that is at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99%, at least about 99.5%, or about 100% identical to a 16S rDNA sequence set forth in SEQ ID NOs: 1-352.
[0163] In some aspects, a bacterial composition disclosed herein (e.g., designed compositions) comprises both a spore-forming bacteria and a non-spore-forming bacteria. In some aspects, a bacterial composition comprises only spore-forming bacteria. In some cases, the bacteria of the compositions are in spore form. In some aspects, a bacterial composition useful for the present disclosure comprises a plurality of bacteria, wherein one or more of the plurality of bacteria are in a spore form and one or more of the plurality of bacteria are in a vegetative form.
[0164] In some aspects, a bacterial composition provided herein is administered to a subject as a pharmaceutical formulation. For instance, in some aspects, a bacterial composition as described herein is combined with additional active and / or inactive materials to produce a formulation. In some aspects, a bacterial composition is formulated in a unit dosage form, each dosage form containing, e.g., from about 102to about 109CFUs, for example, about 104to about 108CFUs. As described herein, in some aspects, all the bacteria of a composition described herein can be formulated as spores. In some aspects, the spores can be formulated as lyophilized spores. In some aspects, the spores can be suspended in a cryoprotectant, for example glycerol. In some aspects, all the bacteria of a composition described herein can be vegetative cells. In some aspects, a bacterial composition described herein can comprise a mixture of spores and vegetative bacteria. In some aspects, bacterialspores and vegetative bacteria can be formulated at the same dosage. In some aspects, bacterial spores and vegetative bacteria can be formulated at different dosages. For example, when a bacterial composition comprises both bacterial spores and vegetative bacteria, the vegetative bacteria can be formulated at a higher dose compared to the bacterial spores. In some aspects, the bacterial spores are formulated at a higher dose compared to the vegetative bacteria. In some aspects, a bacterial composition is formulated in a multi-dose format. Formulations and methods of formulating that can be used with the bacterial compositions described herein are described in U. S. Publ. No. 20220017853A1, which is incorporated by reference herein in its entirety.
[0165] As demonstrated herein, in some aspects, a plurality of bacteria provided herein can be administered to a subject in multiple formulations (e.g., two or more formulations). In some aspects, multiple formulations can comprise two separate formulations ( / .<., a first formulation and a second formulation). For instance, in some aspects, a first formulation comprises one or more of the plurality of bacteria and the second formulation comprises the remaining portion of the plurality of bacteria. Where multiple formulations are involved, in some aspects, some or all of the multiple formulations can be administered to the subject concurrently. For instance, in some aspects, a method provided herein comprises administering a first formulation and a second formulation (such as those described herein), wherein the first formulation and the second formulation are administered to the subject concurrently. In some aspects, some or all of the multiple formulations are administered to the subject sequentially. For instance, in some aspects, a method provided herein comprises administering a first formulation and a second formulation (such as those described herein), wherein the first formulation and the second formulation are administered to the subject sequentially.
[0166] As demonstrated herein, in some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria. In some aspects, the first plurality of bacteria and the second plurality of bacteria are different. For instance, in some aspects, each of the first plurality of bacteria is different from each of the second plurality of bacteria. In some aspects, the first plurality of bacteria comprise both a spore-forming bacteria and a non-spore-forming bacteria. In some aspects, the second plurality of bacteria comprise both a spore-forming bacteria and a non-spore-forming bacteria. In some aspects,both the first plurality of bacteria and the second plurality of bacteria comprise both a sporeforming bacteria and a non-spore-forming bacteria. In some aspects, the first plurality of bacteria comprise only spore-forming bacteria. In some aspects, the second plurality of bacteria comprise only spore-forming bacteria. In some aspects, both the first plurality of bacteria and the second plurality of bacteria comprise only spore-forming bacteria. In some aspects, the first plurality of bacteria comprise one or more bacteria that are in a spore form. In some aspects, the second plurality of bacteria comprise one or more bacteria that are in a spore form. In some aspects, the first plurality of bacteria comprise one or more bacteria that are in a spore form and the second plurality of bacteria comprise one or more bacteria that are in a spore form. In some aspects, each of the first plurality of bacteria is in a spore form. In some aspects, each of the first plurality of bacteria is in a vegetative form. In some aspects, each of the second plurality of bacteria is in a spore form. In some aspects, each of the second plurality of bacteria is in a vegetative form.
[0167] In some aspects, each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form. Accordingly, in some aspects, a method provided herein comprises administering to a subject in need thereof a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form. In some aspects, a first plurality of bacteria is formulated as a liquid (z.e., liquid formulation). In some aspects, a second plurality of bacteria is formulated as a liquid formulation. In some aspects, a first plurality of bacteria is formulated as a dry powder (z.e., dry powder formulation). In some aspects, a second plurality of bacteria is formulated as a dry powder formulation. In some aspects, a first plurality of bacteria is formulated as a liquid formulation and one or more of the first plurality of bacteria are in a spore form. In some aspects, a first plurality of bacteria is formulated as a liquid formulation and each of the first plurality of bacteria is in a spore form. In some aspects, a second plurality of bacteria is formulated as a dry powder formulation and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a second plurality of bacteria is formulated as a dry powder formulation and each of the second plurality of bacteria is in a vegetative form. Accordingly, in some aspects, a method provided herein comprises administering to a subject in need thereof a first formulation comprising a first plurality of bacteria and a second formulation comprisesa second plurality of bacteria, wherein the first formulation is a liquid formulation and one or more of the first plurality of bacteria are in a spore form, and wherein the second formulation is a dry powder formulation and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a method provided herein comprises administering to a subject in need thereof a first formulation comprising a first plurality of bacteria and a second formulation comprises a second plurality of bacteria, wherein the first formulation is a liquid formulation and each of the first plurality of bacteria is in a spore form, and wherein the second formulation is a dry powder formulation and each of the second plurality of bacteria is in a vegetative form.
[0168] In some aspects, a first formulation and / or second formulation can comprise any of the bacteria provided herein. Accordingly, in some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more of the bacterial species provided in FIG. 9 with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same. Unless indicated otherwise, in some aspects, a first plurality of bacteria and a second plurality of bacteria are not the same if one or more of the first plurality of bacteria are not present in the second plurality of bacteria. In some aspects, a first plurality of bacteria and a second plurality of bacteria are not the same if each of the first plurality of bacteria is not present in the second plurality of bacteria. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more of the bacterial species provided in FIG.9 with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same, and wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria and the second plurality ofbacteria comprise one or more of the bacterial species provided in FIG. 9 with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same, and wherein each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form.
[0169] In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, and wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more of the bacterial species present in any of DE1- DE54 compositions with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more of the bacterial species present in any of DE1-DE54 compositions with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same, and wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more of the bacterial species present in any of DE1-DE54 compositions with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same, and wherein each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form.
[0170] In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, and wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more bacteria having at least about 97%, e.g., at least 97%, at least 97.5%, at least 98%, at least 98.5%, at least 99%, or 100% identity to a 16S rDNA sequence (e.g., a full length or variable region of a 16S DNA sequence) to one ormore of the following bacterial species: Eubacterium maltosivorans, Clostridium aldenense, Clostridium bolteae, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium symbiosum, Eubacterium rectale, Ruminococcus gnavus, Ruminococcus torques, Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lachnospiraceae bacterium 5_1_57FAA, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium butyricum, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, Clostridium disporicum, Clostridium subterminale, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, or Ruminococcus lactaris with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is aliquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more bacteria having at least about 97%, e.g., at least 97%, at least 97.5%, at least 98%, at least 98.5%, at least 99%, or 100% identity to a 16S rDNA sequence (e.g., a full length or variable region of a 16S DNA sequence) to one or more of the following bacterial species: Eubacterium maltosivorans, Clostridium aldenense, Clostridium bolteae, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium symbiosum, Eubacterium rectale, Ruminococcus gnavus, Ruminococcus torques, Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lachnospiraceae bacterium 5_1_57FAA, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium butyricum, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, Clostridium disporicum, Clostridium subterminale, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii,Ruminococcus faecis, or Ruminococcus lactaris with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same, and wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria and the second plurality of bacteria comprise one or more bacteria having at least about 97%, e.g., at least 97%, at least 97.5%, at least 98%, at least 98.5%, at least 99%, or 100% identity to a 16S rDNA sequence (e.g., a full length or variable region of a 16S DNA sequence) to one or more of the following bacterial species: Eubacterium maltosivorans, Clostridium aldenense, Clostridium bolteae, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium symbiosum, Eubacterium rectale, Ruminococcus gnavus, Ruminococcus torques, Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphila, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lachnospiraceae bacterium 5_1_57FAA, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium butyricum, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, Clostridium disporicum, Clostridium subterminale, Clostridium tertium,Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, or Ruminococcus lactaris with the proviso that the first plurality of bacteria and the second plurality of bacteria are not the same, and wherein each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form.
[0171] In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first plurality of bacteria comprises one or more of the following bacteria: Clostridium innocuum, Clostridium bolteae, Blautia hominis, Clostridium scindens, Anaerotruncus colihominis, Murimonas intestini, Erysipelatoclostridium ramosum, Faecalicatena ortica, Emergencia timonensis, Clostridium aldenense, and Eisenbergiella tayi, and wherein the second plurality of bacteria comprises one or more of the following bacteria: Blautia wexlerae, Eubacterium callanderi, Flavonifractor plautii, Dorea longicatena, and Blautia obeum. Unless indicated otherwise, in some aspects, (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridiumscindens referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 97%sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p). In some aspects, (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNAsequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ IDNO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p). In some aspects, (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one ofSEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p). In some aspects, (a) the Clostridium innocuum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises the 16SrDNA sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 42, SEQID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
[0172] In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria comprises one or more of the following bacteria: Clostridium innocuum, Clostridium boheae. Blautia hominis. Clostridium scindens. Anaerotruncus colihominis, Murimonas inleslini. Erysipelatoclostridium ramosum. Faecalicatena orlica. Emergencia limonensis. Clostridium aldenense. and Eisenbergiella tayi, wherein the second plurality of bacteria comprises one or more of the following bacteria: Blautia wexlerae, Eubacterium callanderi. Flavonifractor plautii, Dorea longicalena. and Blautia obeum, and wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria comprises one or more of the following bacteria: Clostridium innocuum, Clostridium bolteae, Blautia hominis, Clostridium scindens, Anaerotruncus colihominis, Murimonas intestini, Erysipelatoclostridium ramosum, Faecalicatena ortica, Emergencia timonensis, Clostridium aldenense, and Eisenbergiella tayi, and wherein each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form.
[0173] In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first plurality of bacteria comprises Clostridium innocuum, Clostridium bolteae, Blautia hominis, Clostridium scindens, Anaerotruncus colihominis, Murimonas intestini, Erysipelatoclostridium ramosum, Faecalicatena ortica,Emergencia timonensis, Clostridium aldenense, and Eisenbergiella tayi, and wherein the second plurality of bacteria comprises Blautia wexlerae, Eubacterium callanderi, Flavonifractor plautii, Dorea longicatena, and Blautia obeum. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria comprises Clostridium innocuum, Clostridium boheae, Blautia hominis, Clostridium scindens. Anaerotruncus colihominis, Murimonas inleslini, Erysipelatoclostridium ramosum. Faecalicatena orlica, Emergencia timonensis, Clostridium aldenense, and Eisenbergiella tayi, wherein the second plurality of bacteria comprises Blautia wexlerae, Eubacterium callanderi, Flavonifractor plautii, Dorea longicatena, and Blautia obeum, and wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation is a liquid formulation and the second formulation is a dry powder formulation, wherein the first plurality of bacteria comprises Clostridium innocuum, Clostridium bolteae, Blautia hominis, Clostridium scindens, Anaerotruncus colihominis, Murimonas intestini, Erysipelatoclostridium ramosum, Faecalicatena ortica, Emergencia timonensis, Clostridium aldenense, and Eisenbergiella tayi, wherein the second plurality of bacteria comprises Blautia wexlerae, Eubacterium callanderi, Flavonifractor plautii, Dorea longicatena, and Blautia obeum, and wherein each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form.
[0174] Where multiple formulations are administered to a subject, in some aspects, the multiple formulations are in a unit dosage form, each dosage form containing, e.g., from about 102to about 1012colony forming units (CFUs) of bacteria per milligram (mg), for example, about 104to about IO10CFUs of bacteria. For example, in some aspects, multiple formulations comprise a first formulation and a second formulation, wherein the first formulation is administered at a dose from about 102to about 1012CFUs of bacteria, and wherein the second formulation is administered at a dose from about 102to about 1012CFUs of bacteria. In some aspects, the dose of the first formulation is about 102CFUs, about 103CFUs, about 104CFUs, about 105CFUs, about 106CFUs, about 107CFUs, about 108CFUs, about 109CFUs, IO10CFUs, about 1011CFUs, or about 1012CFUs, and the dose of the second formulation is about 102CFUs, about 103CFUs, about 104CFUs, about 105CFUs, about 106CFUs, about 107CFUs, about 108CFUs, about 109CFUs, IO10CFUs, about 1011CFUs, or about 1012CFUs. In some aspects, the dose of the first formulation is about 105CFUs to 107CFUs, and the dose of the second formulation is about 105CFUs to 107CFUs. In some aspects, the dose of the first formulation and the dose of the second formulation are the same. In some aspects, the dose of the first formulation and the dose of the second formulation are different. For instance, in some aspects, the dose of the first formulation is greater than the dose of the second formulation. In some aspects, the dose of the first formulation is less than the dose of the second formulation. In some aspects, the dose of the first formulation is about 105CFUs to 107CFUs, and the dose of the second formulation is about 106CFUs to 108CFUs. In some aspects, the dose of the first formulation is about 106CFUs of bacteria, and the dose of the second formulation is about 107CFUs of bacteria. In some aspects, the dose of the first formulation is about 6.9 x 106CFUs of bacteria, and the dose of the second formulation is about 3.1 x 107CFUs of bacteria.
[0175] As described herein, a formulation described herein (e.g., first formulation and / or second formulation) can comprise one or more excipients. In some aspects, the one or more excipients comprise urea. In some aspects, the urea is at a concentration (w / w) of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 2.0%, about 3.0%, about 4.0%, or about 5.0% or more. In some aspects, the urea is at a concentration (w / w) of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, or about 1.0%. In some aspects, the urea is at a concentration (w / w) of about 0.5%. In some aspects, the urea is at a concentration (w / w) of about 1.0%. In some aspects, a formulation provided herein comprises about 0.1-5 mg of urea. In some aspects, a formulation provided herein comprises about 0.5-4 mg of urea. In some aspects, a formulation provided herein comprises about 0.3-1 mg of urea.
[0176] Examples of formulations comprising urea are provided in U. S. Publication No.20220017853 Al, which is incorporated herein by reference in its entirety. Additional examples of suitable excipients are provided throughout the present disclosure and alsodescribed in U. S. Publication No. 20220017853 Al. In some aspects, a formulation suitable for the present disclosure comprises a diluent (e.g., glycerol and phosphate-buffered saline (PBS)). Accordingly, in some aspects, a formulation provided herein comprises a plurality of bacteria (e.g., described herein) and glycerol. In some aspects, a formulation provided herein comprises a plurality of bacteria (e.g., described herein) and PBS. In some aspects, a formulation provided herein comprises a plurality of bacteria (e.g., described herein), urea, a cryoprotectant (e.g., sucrose), an antioxidant (e.g., ascorbic acid and cysteine hydrochloride monohydrate), a protein stabilizer (e.g., gelatin hydrolysate), a salt (e.g., potassium chloride), a buffer (e.g., HEPES), a neutralizing agent (e.g., sodium hydroxide), a bulking agent (e.g., microcrystalline cellulose), a glidant (e.g., hydrophobic colloidal silica), a lubricant (e.g., sodium stearyl fumarate), or any combination thereof. In some aspects, a formulation provided herein comprises a plurality of bacteria (e.g., described herein), urea, sucrose, ascorbic acid, cysteine hydrochloride monohydrate, gelatin hydrolysate, potassium chloride, HEPES, sodium hydroxide, microcrystalline cellulose, hydrophobic colloidal silica, and sodium stearyl fumarate.
[0177] In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria (e.g., described herein) and a second formulation comprising a second plurality of bacteria (e.g., described herein), wherein the first formulation further comprises glycerol, PBS, or both, wherein the second formulation further comprises urea, a cryoprotectant (e.g., sucrose), an antioxidant (e.g., ascorbic acid and cysteine hydrochloride monohydrate), a protein stabilizer (e.g., gelatin hydrolysate), a salt (e.g., potassium chloride), a buffer (e.g., HEPES), a neutralizing agent (e.g., sodium hydroxide), a bulking agent (e.g., microcrystalline cellulose), a glidant (e.g., hydrophobic colloidal silica), a lubricant (e.g., sodium stearyl fumarate), or any combination thereof, wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria (e.g., described herein) and a second formulation comprising a second plurality of bacteria (e.g., described herein), wherein the first formulation further comprises glycerol, PBS, or both, wherein the second formulation further comprises urea, a cryoprotectant (e.g., sucrose), an antioxidant (e.g, ascorbic acid and cysteine hydrochloride monohydrate), a protein stabilizer (e.g, gelatin hydrolysate), a salt (e.g., potassium chloride), a buffer (e.g.,HEPES), a neutralizing agent (e.g., sodium hydroxide), a bulking agent (e.g., microcrystalline cellulose), a glidant (e.g., hydrophobic colloidal silica), a lubricant (e.g., sodium stearyl fumarate), or any combination thereof, wherein each of the first plurality of bacteria is in a spore form and each of the second plurality of bacteria is in a vegetative form. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation further comprises glycerol, PBS, or both, wherein the second formulation further comprises urea, a cryoprotectant (e.g., sucrose), an antioxidant (e.g., ascorbic acid and cysteine hydrochloride monohydrate), a protein stabilizer (e.g., gelatin hydrolysate), a salt (e.g., potassium chloride), a buffer (e.g., HEPES), a neutralizing agent (e.g., sodium hydroxide), a bulking agent (e.g., microcrystalline cellulose), a glidant (e.g., hydrophobic colloidal silica), a lubricant (e.g., sodium stearyl fumarate), or any combination thereof, wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form, wherein the first plurality of bacteria comprises one or more of the following bacteria: Clostridium innocuum, Clostridium bolteae, Blautia hominis, Clostridium scindens, Anaerotruncus colihominis, Murimonas intestini, Erysipelatoclostridium ramosum, Faecalicatena ortica, Emergencia timonensis, Clostridium aldenense, and Eisenbergiella tayi, and wherein the second plurality of bacteria comprises one or more of the following bacteria: Blautia wexlerae, Eubacterium callander i, Flavonifractor plautii, Dorea longicatena, and Blautia obeum. In some aspects, a method provided herein comprises administering a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first formulation further comprises glycerol, PBS, or both, wherein the second formulation further comprises urea, a cryoprotectant (e.g., sucrose), an antioxidant (e.g., ascorbic acid and cysteine hydrochloride monohydrate), a protein stabilizer (e.g., gelatin hydrolysate), a salt (e.g., potassium chloride), a buffer (e.g., HEPES), a neutralizing agent (e.g., sodium hydroxide), a bulking agent (e.g., microcrystalline cellulose), a glidant (e.g., hydrophobic colloidal silica), a lubricant (e.g., sodium stearyl fumarate), or any combination thereof, wherein one or more of the first plurality of bacteria are in a spore form and one or more of the second plurality of bacteria are in a vegetative form, wherein the first plurality of bacteria comprises Clostridium innocuum, Clostridium bolteae, Blautiahominis, Clostridium scindens, Anaerotruncus colihominis, Murimonas intestine Erysipelatoclostridium ramosum. Faecalicatena orlica. Emergencia limonensis. Clostridium aldenense. and Eisenbergiella tayi, and wherein the second plurality of bacteria comprises Blautia wexlerae. Eubacterium caHanderi. Flavonifractor plautii, Dorea longicalena. and Blautia obeum.
[0178] As described herein, in some aspects, a formulation provided herein (e.g., first formulation and / or second formulation) comprises a cryoprotectant. In some aspects, a cryoprotectant is a sugar. In some aspects, the sugar is a di saccharide, such as sucrose, trehalose, lactose, glucose, fructose, galactose, dextrose, maltose, cellobiose, chitobiose, or lactulose. In some aspects, the sugar is sucrose. In some aspects, the cryoprotectant (e.g., sugar, e.g., sucrose) is present at a concentration (w / w) of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, or about 25% or more. In some aspects, the cryoprotectant (e.g., sugar, e.g., sucrose) is present in the formulation at an amount between about 5-80 mg. In some aspects, a formulation provided herein comprises about 10-77 mg of cryoprotectant (e.g., sugar, e.g., sucrose). In some aspects, a formulation provided herein comprises about 7-55 mg of cryoprotectant (e.g., sugar, e.g., sucrose).
[0179] As described herein, in some aspects, a formulation provided herein (e.g., first formulation and / or second formulation) comprises an antioxidant. In some aspects, an antioxidant comprises cysteine, ascorbic acid, or both. In some aspects, an antioxidant is cysteine (e.g., cysteine hydrochloride monohydrate). In some aspects, cysteine (e.g., cysteine hydrochloride monohydrate) is present in a formulation disclosed herein at a concentration of about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.55%, about 0.6%, about 0.65%, about 0.7%, about 0.75%, about 0.8%, about 0.85%, about 0.9%, about 0.95%, or about 1.0% or more. In some aspects, cysteine (e.g., cysteine hydrochloride monohydrate) is present at a concentration of about 0.25%. In some aspects, a formulation provided herein comprises a trace amount of cysteine (e.g., cysteine hydrochloride monohydrate).
[0180] In some aspects, an antioxidant is ascorbic acid. In some aspects, ascorbic acid is at a concentration of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about- Ill -0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, or about 2.0% or more. In some aspects, ascorbic acid is present at a concentration of about 1.0%. In some aspects, a formulation provided herein comprises about 1-10 mg of ascorbic acid. In some aspects, a formulation provided herein comprises about 1-8 mg of ascorbic acid. In some aspects, a formulation provided herein comprises about 1-6 mg of ascorbic acid.
[0181] As also described herein, in some aspects, a formulation provided herein (e.g., first formulation and / or second formulation) comprises a protein stabilizer. In some aspects, a protein stabilizer comprises a gelatin (e.g., gelatin hydrolysate). In some aspects, a formulation provided herein comprises about 1-25 mg of a protein stabilizer (e.g., gelatin, e.g, gelatin hydrolysate). In some aspects, a formulation provided herein comprises about 3-23 mg of a protein stabilizer (e.g., gelatin, e.g., gelatin hydrolysate). In some aspects, a formulation provided herein comprises about 2-16 mg of a protein stabilizer (e.g., gelatin, e.g., gelatin hydrolysate).
[0182] In some aspects, a formulation provided herein (e.g., first formulation and / or second formulation) comprises a salt. In some aspects, a salt comprises potassium chloride (KC1). In some aspects, the salt (e.g., KC1) is present in a formulation disclosed herein at a concentration of about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, or about 50 mM. In some aspects, a formulation comprises about 0.1-2 mg of a salt (e.g., KC1). In some aspects, a formulation comprises about 0.2- 1.4 mg of a salt (e.g., KC1). In some aspects, a formulation comprises about 0.1-1 mg of a salt (e.g., KC1).
[0183] In some aspects, a formulation provided herein comprises a buffering agent. In some aspects, a buffering agent comprises HEPES. In some aspects, a formulation disclosed herein comprises a buffering agent (e.g., HEPES) at a concentration of about 1 mM, about 2 mM, about 3 mM, about 4 mM, about 5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, about 10 mM, about 15 mM, about 20 mM, about 30 mM, about 40 mM, about 50 mM, about 60 mM, about 70 mM, about 80 mM, about 90 mM, about 100 mM, about 150 mM, or about 200 mM. In some aspects, the buffering agent (e.g., HEPES) is present at a concentration between about 10 mM and about 100 mM. In some aspects, the buffering agent (e.g., HEPES) is present at a concentration of about 50 mM. In some aspects, a formulation provided herein comprises about 0.1-10 mg of a buffering agent(e.g., HEPES). In some aspects, a formulation provided herein comprises about 1.1-9 mg of a buffering agent (e.g., HEPES). In some aspects, a formulation provided herein comprises about 0.3-3 mg of a buffering agent (e.g., HEPES).
[0184] In some aspects, a formulation provided herein comprises a neutralizing agent. In some aspects, a neutralizing agent is sodium hydroxide. In some aspects, a formulation provided herein comprises a trace amount of a neutralizing agent (e.g., sodium hydroxide).
[0185] In some aspects, a formulation provided herein comprises a bulking agent. In some aspects, a bulking agent comprises cellulose (e.g., microcrystalline cellulose). In some aspects, a formulation provided herein comprises about 150-300 mg of a bulking agent (e.g., cellulose, e.g., microcrystalline cellulose). In some aspects, a formulation provided herein comprises about 181-287 mg of a bulking agent (e.g., cellulose, e.g., microcrystalline cellulose). In some aspects, a formulation provided herein comprises about 125-201 mg of a bulking agent (e.g., cellulose, e.g., microcrystalline cellulose).
[0186] In some aspects, a formulation provided herein comprises a glidant. In some aspects, a glidant comprises silica (e.g., hydrophobic colloidial silica). In some aspects, a formulation provided herein comprises about 0.1-1 mg of a glidant (e.g., silica, e.g., hydrophobic collo...
Claims
WHAT IS CLAIMED IS:
1. A method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; and wherein the reference subject comprises a corresponding subject who did not receive an administration of the composition.
2. The method of claim 1, wherein the preventing and / or reducing a risk of a bloodstream infection comprises reducing an incidence of the bloodstream infection in the subject.
3. A method of reducing and / or preventing a pathogen domination within the gastrointestinal tract of a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; and wherein the reference subject comprises a corresponding subject who did not receive an administration of the composition.
4. A method of repairing and / or protecting a gut epithelial barrier in a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof; and wherein the reference subject comprises a corresponding subject who did not receive an administration of the composition.
5. A method of regulating an inflammatory response in a subject in need thereof, comprising administering to the subject a composition comprising a plurality of bacteria, wherein the subject exhibits an expression of a marker that is altered (increased or decreased) as compared to a reference subject, wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, orcombinations thereof; and wherein the reference subject comprises a corresponding subject who did not receive an administration of the composition.
6. The method of claim 5, wherein after the administering, the inflammatory response is reduced in the subject.
7. The method of any one of claims 1 to 6, wherein as compared to the reference subject, the expression of the marker is increased in the subject.
8. The method of claim 7, wherein after the administering, the expression of the marker is decreased in the subject.
9. The method of any one of claims 1 to 6, wherein as compared to the reference subject, the expression of the marker is decreased in the subject.
10. The method of claim 9, wherein after the administering, the expression of the marker is increased in the subject.
11. The method of any one of claims 1 to 10, wherein the plurality of bacteria comprises Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphda, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae, Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium bolteae, Clostridium butyricum, Clostridium disporicum, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium sub terminale, Clostridium symbiosum, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium maltosivorans,Eubacterium rectale, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, or any combination thereof.
12. The method of any one of claims 1 to 11, wherein the plurality of bacteria comprises a 16S rDNA sequence that shares at least 97% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352.
13. The method of any one of claims 1 to 12, wherein the plurality of bacteria comprises a 16S rDNA sequence that shares at least 98% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352.
14. The method of any one of claims 1 to 13, wherein the plurality of bacteria comprises a 16S rDNA sequence that shares at least 99% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352.
15. The method of any one of claims 1 to 14, wherein the plurality of bacteria comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 1 to 352.
16. The method of any one of claims 2 and 7 to 15, wherein the bloodstream infection comprises an infection with an ESKAPE pathogen.
17. The method of any one of claims 2 and 7 to 16, wherein the bloodstream infection comprises an opportunistic infection with a commensal bacterial species.
18. The method of any one of claims 2 and 7 to 17, wherein the bloodstream infection comprises an infection with an antibiotic resistant bacterial species.
19. The method of any one of claims 1 to 18, wherein the subject has an immunodeficiency.
20. The method of any one of claims 1 to 19, wherein the subject has a non-bloodstream infection.
21. The method of any one of claims 1 to 20, wherein the subject has a gut dysbiosis or disruption.
22. The method of claim 21, wherein the dysbiosis comprises a gut dysbiosis or disruption, an oral dysbiosis or disruption, or both.
23. The method of any one of claims 1 to 22, wherein the subject has received, is receiving, or will receive an allogeneic hematopoietic stem cell transplantation (allo-HSCT).
24. The method of any one of claims 1 to 23, wherein one or more of the plurality of bacteria are lyophilized.
25. The method of any one of claims 1 to 24, wherein the composition is formulated for oral delivery.
26. The method of any one of claims 1 to 25, wherein the composition comprises a capsule.
27. The method of any one of claims 1 to 26, wherein the composition comprises an enteric polymer.
28. The method of any one of claims 1 to 27, comprising administering multiple doses of the composition to the subject.
29. The method of any one of claims 1 to 28, wherein one or more of the plurality of bacteria are in a spore form.
30. The method of any one of claims 1 to 29, wherein one or more of the plurality of bacteria are in a vegetative form.
31. A method of identifying a subject who is likely to favorably respond to a composition comprising a plurality of bacteria, wherein the method comprises determining an expression of a marker in a biological sample obtained from the subject,wherein the subject is identified as likely to favorably respond to the composition if the expression of the marker is altered (decreased or increased) as compared to a reference subject,wherein the reference subject comprises a corresponding subject who does not favorably respond to the composition, andwherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof.
32. The method of claim 31, further comprising administering the composition to the subject who has been identified as likely to favorably respond to the composition.
33. A method of identifying a subject who is responding to a composition comprising a plurality of bacteria, comprising determining an expression of a marker in a biological sample obtained from the subject,wherein the marker comprises fecal albumin, myeloperoxidase, TNFR1, IL2Ra (CD25), elafin, CK-18, HGF, CD146, CCR5, a4p7, or combinations thereof;wherein prior to the determining, the subject has received an administration of the composition;wherein the subject is responding to the composition if the expression of the marker is altered (decreased or increased) as compared to a reference subject; andwherein the reference subject is: (a) the subject prior to the administration of the composition, (b) a corresponding subject who did not previously receive an administration of the composition, or (c) both (a) and (b).
34. The method of claim 33, which comprises administering an additional dose of the composition to the subject if the subject is responding to the composition.
35. The method of any one of claims 31 to 34, wherein the plurality of bacteria comprises Absiella dolichum, Agathobaculum desmolans, Akkermansia muciniphda, Alistipes finegoldii, Alistipes shahii, Anaerofustis stercorihominis, Anaeromassilibacillus senegalensis, Anaerostipes caccae, Anaerotruncus colihominis, Bacteroides caccae,Bacteroides eggerthii, Bacteroides faecis, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides salyersiae, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Barnesiella intestinihominis, Bifidobacterium dentium, Bifidobacterium longum, Bifidobacterium stercoris, Blautia coccoides, Blautia hominis, Blautia hydrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia wexlerae, Butyricimonas faecihominis, Cellulosilyticum lentocellum, Clostridium aldenense, Clostridium bolteae, Clostridium butyricum, Clostridium disporicum, Clostridium glycyrrhizinilyticum, Clostridium hylemonae, Clostridium innocuum, Clostridium lavalense, Clostridium scindens, Clostridium spiroforme, Clostridium sub terminale, Clostridium symbiosum, Clostridium tertium, Collinsella aerofaciens, Coprococcus comes, Coprococcus eutactus, Dorea longicatena, Drancourtella massiliensis, Eggerthella lenta, Eisenbergiella tayi, Emergencia timonensis, Erysipelatoclostridium ramosum, Eubacterium callanderi, Eubacterium maltosivorans, Eubacterium rectale, Faecalibacterium prausnitzii, Faecalicatena contorta, Faecalicatena orotica, Flavonifractor plautii, Gemmiger formicilis, Harryflintia acetispora, Holdemania filiformis, Holdemania massiliensis, Intestinimonas butyriciproducens, Lachnospira pectinoschiza, Lactobacillus fermentum, Lactonifactor longoviformis, Longibaculum muris, Longicatena caecimuris, Murimonas intestini, Oscillibacter ruminantium, Paeniclostridium sordellii, Parabacteroides distasonis, Parabacteroides merdae, Paraclostridium bifermentans, Peptostreptococcus stomatis, Robinsoniella peoriensis, Romboutsia timonensis, Roseburia intestinalis, Roseburia inulinivorans, Ruminococcus albus, Ruminococcus bromii, Ruminococcus faecis, Ruminococcus gnavus, Ruminococcus lactaris, Ruminococcus torques, Ruthenibacterium lactatiformans, Sellimonas intestinalis, Shigella flexneri, Terrisporobacter mayombei, Terrisporobacter petrolearius, Turicibacter sanguinis, Tyzzerella nexilis, or any combination thereof.
36. The method of any one of claims 31 to 35, wherein the plurality of bacteria comprises a 16S rDNA sequence that shares at least 97% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352.
37. The method of any one of claims 31 to 36, wherein the plurality of bacteria comprises a 16S rDNA sequence that shares at least 98% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352.
38. The method of any one of claims 31 to 37, wherein the plurality of bacteria comprises a 16S rDNA sequence that shares at least 99% sequence identity with the sequence set forth in any one of SEQ ID NOs: 1 to 352.
39. The method of any one of claims 31 to 38, wherein the plurality of bacteria comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 1 to 352.
40. The method of any one of claims 31 to 39, wherein the subject has received, is receiving, or will receive an allogeneic hematopoietic stem cell transplantation (allo-HSCT).
41. The method of any one of claims 31 to 40, wherein the subject has a bloodstream infection.
42. The method of claim 41, wherein the bloodstream infection comprises an infection with an ESKAPE pathogen.
43. The method of claim 41 or 42, wherein the bloodstream infection comprises an opportunistic infection with a commensal bacterial species.
44. The method of any one of claims 41 to 43, wherein the bloodstream infection comprises an infection with an antibiotic resistant bacterial species.
45. The method of any one of claims 31 to 44, wherein one or more of the plurality of bacteria are lyophilized.
46. The method of any one of claims 31 to 45, wherein the composition is formulated for oral delivery.
47. The method of any one of claims 31 to 46, wherein the composition comprises a capsule.
48. The method of any one of claims 31 to 47, wherein the composition comprises an enteric polymer.
49. The method of any one of claims 31 to 48, wherein one or more of the plurality of bacteria are in a spore form.
50. The method of any one of claims 31 to 49, wherein one or more of the plurality of bacteria are in a vegetative form.
51. The method of any one of claims 1 to 50, wherein the plurality of bacteria is formulated as two parts, wherein the part 1 comprises a liquid formulation of bacterial spores and the part 2 comprises a dry powder formulation of vegetative bacteria.
52. The method of claim 51, wherein the part 1 comprises the following strains: Clostridium innocuum: Clostridium boheae Blautia hominis: [Clostridium] scindens: Anaerotruncus coUhominis Murimonas inleslini: Erysipelatoclostridium ramosum: Faecalicatena orlica: Emergencia limonensis: Clostridium aldenense: and Eisenbergiella tayi.
53. The method of claim 52, wherein the strains are delivered at a target dose strength of 6.9 x 106colony-forming units (CFUs) per dose.
54. The method of any one of claim 51 to 53, wherein the part 2 comprises the following strains:Blautia wexlerae: Eubacterium callanderi: Flavonifr actor plaulii Dorea longicalena and Blautia obeum.
55. The method of claim 54 wherein the strains are delivered at a target dose strength of 3.1 x 107CFUs per dose.
56. A composition comprising a first formulation comprising a first plurality of bacteria and a second formulation comprising a second plurality of bacteria, wherein the first plurality of bacteria comprises one or more of the following bacteria: Clostridium innocuum, Clostridium boheae, Blautia hominis, Clostridium scindens, Anaerotruncus coUhominis, Murimonas intestini, Erysipelatoclostridium ramosum, Faecalicatena ortica, Emergencia timonensis, Clostridium aldenense, and Eisenbergiella tayi, and wherein the second plurality of bacteria comprises one or more of the following bacteria: Blautia wexlerae, Eubacterium callanderi, Flavonifractor plautii, Dorea longicatena, and Blautia obeum.
57. The composition of claim 56, wherein one or more bacteria of the first plurality of bacteria are in a spore form.
58. The composition of claim 57, wherein each of the bacteria of the first plurality of bacteria is in a spore form.
59. The composition of any one of claims 56 to 58, wherein one or more bacteria of the second plurality of bacteria are in a vegetative form.
60. The composition of claim 59, wherein each of the bacteria of the second pluarity of bacteria is in a vegetative form.
61. The composition of any one of claims 56 to 60, wherein the first formulation is a liquid formulation.
62. The composition of any one of claims 56 to 61, wherein the second formulation is a dry powder formulation.
63. The composition of any one of claims 56 to 62, wherein a dose of the first formulation is about 6.9 x 106CFUs of bacteria.
64. The composition of any one of claims 56 to 63, wherein a dose of the second formulation is about 3.1 x 107CFUs of bacteria.
65. The composition of any one of claims 56 to 64, wherein the first formulation comprises glycerol.
66. The composition of any one of claims 56 to 65, wherein the second formulation comprises urea.
67. The composition of any one of claims 56 to 66, wherein the second formulation comprises a cryoprotectant.
68. The composition of claim 67, wherein the cryoprotectant comprises a sugar.
69. The composition of claim 68, wherein the sugar comprises sucrose.
70. The composition of any one of claims 56 to 69, wherein the second formulation comprises an antioxidant.
71. The composition of claim 70, wherein the antioxidant comprises ascorbic acid, cysteine, or both.
72. The composition of claim 71, wherein the cysteine comprises cysteine hydrochloride monohydrate.
73. The composition of any one of claims 56 to 72, wherein the second formulation comprises a protein stabilizer.
74. The composition of claim 73, wherein the protein stabilizer comprises gelatin.
75. The composition of claim 74, wherein the gelatin comprises gelatin hydrolysate.
76. The composition of any one of claims 56 to 75, wherein the second formulation comprises a salt.
77. The composition of claim 76, wherein the salt comprises potassium chloride.
78. The composition of any one of claims 56 to 77, wherein the second formulation comprises a buffering agent.
79. The composition of claim 78, wherein the buffering agent comprises HEPES.
80. The composition of any one of claims 56 to 79, wherein the second formulation comprises a neutralizing agent.
81. The composition of claim 80, wherein the neutralizing agent comprises sodium hydroxide.
82. The composition of any one of claims 56 to 79, wherien the second formulation comprises a bulking agent.
83. The composition of claim 82, wherein the bulking agent comprises cellulose.
84. The composition of claim 83, wherein the cellulose comprises microcrystalline cellulose.
85. The composition of any one of claims 56 to 84, wherein the second formulation comprises a glidant.
86. The composition of claim 85, wherein the glidant comprises silica.
87. The composition of claim 86, wherein the silica comprises hydrophobic colloidial silica.
88. The composition of any one of claims 56 to 87, wherein the second formulation comprises a lubricant.
89. The composition of claim 88, wherein the lubricant comprises sodium stearyl fumarate.
90. The composition of any one of claims 56 to 89, wherein the first formulation is in a capsule.
91. The composition of any one of claims 56 to 90, wherein the second formulation is in a capsule.
92. The composition of claim 90 or 91, wherein the capsule is enterically coated.
93. The composition of any one of claims 56 to 92, wherein: (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequencethat shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to thesequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 97% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
94. The composition of any one of claims 56 to 93, wherein: (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequencethat shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to thesequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 98% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
95. The composition of any one of claims 56 to 94, wherein: (a) the Clostridium innocuum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises a 16S rDNA sequencethat shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises at 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to thesequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises a 16S rDNA sequence that shares at least 99% sequence identity to the sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
96. The composition of any one of claims 56 to 95, wherein: (a) the Clostridium innocuum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 79, SEQ ID NO: 85, SEQ ID NO: 95, SEQ ID NO: 148, SEQ ID NO: 157, SEQ ID NO: 231, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, and SEQ ID NO: 252; (b) the Clostridium bolteae referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 127, SEQ ID NO: 141, SEQ ID NO: 150, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, and SEQ ID NO: 257; (c) the Blautia hominis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 21, SEQ ID NO: 30, SEQ ID NO: 59, SEQ ID NO: 65, SEQ ID NO: 115, SEQ ID NO: 140, SEQ ID NO: 202, SEQ ID NO: 233, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, and SEQ ID NO: 270; (d) the Clostridium scindens referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 41, SEQ ID NO: 81, SEQ ID NO: 98, SEQ ID NO: 105, SEQ ID NO: 199, SEQ ID NO: 216, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 311, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334, and SEQ ID NO: 335; (e) the Anaerotruncus colihominis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 205, SEQ ID NO: 271, SEQ ID NO: 272, and SEQ ID NO: 273; (f) the Murimonas intestini referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 200, SEQ ID NO: 215, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, and SEQ ID NO: 278; (g) the Erysipelatoclostridium ramosum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 73, SEQ ID NO: 146, SEQ ID NO: 183, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, and SEQ ID NO: 283; (h) the Faecalicatena ortica referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 13, SEQ ID NO: 35, SEQ ID NO: 235, SEQ ID NO: 284,SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 312, and SEQ ID NO: 313; (i) the Emergencia timonensis referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 36, SEQ ID NO: 70, SEQ ID NO: 149, SEQ ID NO: 193, SEQ ID NO: 289, SEQ ID NO: 290, and SEQ ID NO: 291; (j) the Clostridium aldenense referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 44, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, and SEQ ID NO: 326; (k) the Eisenbergiella tayi referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 99, SEQ ID NO: 162, SEQ ID NO: 185, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329, and SEQ ID NO: 330; (1) the Blautia wexlerae referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 4, SEQ ID NO: 120, SEQ ID NO: 222, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, and SEQ ID NO: 247; (m) the Eubacterium callanderi referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 52, SEQ ID NO: 63, SEQ ID NO: 166, SEQ ID NO: 177, SEQ ID NO: 195, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, and SEQ ID NO: 262; (n) the Flavonifractor plautii referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 19, SEQ ID NO: 77, SEQ ID NO: 154, SEQ ID NO: 226, SEQ ID NO: 228, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, and SEQ ID NO: 352; (o) the Dorea longicatena referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 42, SEQ ID NO: 197, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 316, SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321; (p) the Blautia obeum referred to herein comprises the 16S rDNA sequence set forth in any one of SEQ ID NO: 104, SEQ ID NO: 113, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340, and SEQ ID NO: 341; or (q) any combination of (a) to (p).
97. A method of preventing and / or reducing a risk of a bloodstream infection in a subject in need thereof, comprising administering to the subject the composition of any one of claims 56 to 96.
98. A method of reducing and / or preventing a pathogen domination within the gastrointestinal tract of a subject in need thereof, comprising administering to the subject the composition of any one of claims 56 to 96.
99. A method of repairing and / or protecting a gut epithelial barrier in a subject in need thereof, comprising administering to the subject the composition of any one of claims 56 to 96.
100. A method of regulating an inflammatory response in a subject in need thereof, comprising administering to the subject the composition of any one of claims 56 to 96.