PROBIOTIC COMPOSITIONS CONTAINING CLOSTRIDIALES FOR INHIBITING INFLAMMATION
Pharmaceutical compositions containing microbial entities are described herein. The pharmaceutical compositions may optionally contain or be used in conjunction with one or more prebiotics. Uses of the pharmaceutical compositions to treat or prevent disorders of the local or systemic microbiome in a subject are also provided.
1 . A pharmaceutical composition comprising an isolated population of anti-inflammatory bacterial cells of the order Clostridiales capable of decreasing the secretion of a pro-inflammatory cytokine and/or increasing the secretion of an anti-inflammatory cytokine by a population of human peripheral blood mononuclear cells (PBMCs), and a pharmaceutically acceptable excipient.
2 . The pharmaceutical composition of claim 1 , wherein the secretion of a pro-inflammatory cytokine by a population of PBMCs is induced by Enterococcus faecalis.
3 . The pharmaceutical composition of claim 1 , wherein the anti-inflammatory bacterial cells are of the family Lachnospiraceae.
4 . The method of claim 1 , wherein the anti-inflammatory bacterial cells are of the genus Blautia, Clostridium, Eubacterium, or Ruminococcus.
5 . The pharmaceutical composition of claim 4 , wherein the anti-inflammatory bacterial cells are of the genus Blautia.
6 . The pharmaceutical composition of claim 5 , wherein the anti-inflammatory bacterial cells are of a species selected from the group consisting of Blautia coccoides, Blautia faecis, Blautia glucerasea, Blautia hansenii, Blautia hyrogenotrophica, Blautia luti, Blautia obeum, Blautia producta, Blautia schinkii, Blautia sp. M25, Blautia stercoris, Blautia wexlerae, Blautia uncultured bacterium clone BKLE_a03_2, Blautia uncultured bacterium clone SJTU_B_14_30, Blautia uncultured bacterium clone SJTU_C_14_16, Blautia uncultured bacterium clone S1-5, and Blautia uncultured PAC000178_s.
7 . The pharmaceutical composition of claim 4 , wherein the anti-inflammatory bacterial cells are of the species Ruminococcus gnavus or Eubacterium rectale.
8 . The pharmaceutical composition of claim 1 , wherein the anti-inflammatory bacterial cells comprise a bacterial cell in vegetative form or in spore form.
9 . (canceled)
10 . The pharmaceutical composition of claim 1 , wherein the isolated population of anti-inflammatory bacterial cells further comprises a bacterial cell belonging to a bacterial strain set forth in Table 1, Table 1A, Table 1B, Table 1C, Table 1D, Table 1E, or Table 1F.
11 - 13 . (canceled)
14 . The pharmaceutical composition of claim 1 , wherein the pro-inflammatory cytokine is selected from the group consisting of IFNγ, IL-12p′70, IL-1α, IL-6, IL-8, MCP1, MIP 1 α, MIP1β, TNFα, and combinations thereof.
15 . The pharmaceutical composition of claim 1 , wherein the anti-inflammatory cytokine is selected from the group consisting of IL-10, IL-13, IL-4, IL-5, TGFβ, and combinations thereof.
16 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration or rectal administration.
17 . (canceled)
18 . The pharmaceutical composition of claim 1 , wherein the anti-inflammatory bacterial cells decrease the secretion of a pro-inflammatory cytokine and/or increase the secretion of an anti-inflammatory cytokine by a population of human peripheral blood mononuclear cells (PBMCs) in vitro.
19 . A method for reducing inflammation in a subject, the method comprising administering the pharmaceutical composition of claim 1 to the subject, thereby reducing inflammation in the subject.
20 . The method of claim 19 , wherein the subject has an autoimmune or inflammatory disorder.
21 . The method of claim 20 , wherein the autoimmune or inflammatory disorder is selected from the group consisting of graft-versus-host disease (GVHD), an inflammatory bowel disease (IBD), ulterative colitis, Crohn's disease, multiple sclerosis (MS), systemic lupus erythematosus (SLE), type I diabetes, rheumatoid arthritis, Sjögren's syndrome, and Celiac disease.
22 . The method of claim 19 , wherein the pharmaceutical composition is administered orally or rectally.
23 . (canceled)
24 . The method of claim 19 , wherein administration of the pharmaceutical composition reduces inflammation in the gastrointestinal tract of the subject.
25 . The method of claim 19 , wherein administration of the pharmaceutical composition reduces inflammation at a site distal to the gastrointestinal tract of the subject.
26 . The method of claim 19 , wherein the subject has a dysbiosis.
27 . The method of claim 26 , wherein the dysbiosis is a gastrointestinal dysbiosis.
28 . The method of claim 26 , wherein the dysbiosis is a distal dysbiosis.
29 . The method of claim 19 , wherein the anti-inflammatory bacterial cells of the pharmaceutical composition engraft in the gastrointestinal tract of the subject.
30 . (canceled)