Composition for inducing proliferation or accumulation of regulatory T cells
It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.
1. A pharmaceutical composition, comprising a purified bacterial mixture of at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa,
wherein the bacterial mixture induces proliferation and/or accumulation of regulatory T cells, wherein the bacterial strains are spore forming bacteria and are human commensal bacteria, and wherein the pharmaceutical composition is formulated for delivery to the intestine.
2. The pharmaceutical composition of claim 1 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster IV.
3. The pharmaceutical composition of claim 1 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster XIVa.
4. The pharmaceutical composition of claim 1 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise one or more strains belonging to Clostridium cluster IV and one or more strains belonging to Clostridium cluster XIVa.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises one or more bacterial strains belonging to a Clostridium cluster other than Clostridium cluster IV or Clostridium cluster XIVa.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration.
8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in the form of a capsule.
10. The pharmaceutical composition of claim 1 , wherein the bacteria are in the form of spores.
11. A method of treating a human subject having an autoimmune disease, the method comprising administering the composition of claim 1 .
12. The method of claim 11 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, sprue, rheumatoid arthritis, Type 1 diabetes, graft versus host disease, or multiple sclerosis.
13. A method of treating a human subject having an allergic disease, the method comprising administering the composition of claim 1 .
14. A method of treating a human subject having an infectious disease, the method comprising administering the composition of claim 1 .
15. The method of claim 14 , wherein the infectious disease is Clostridium difficile infection.
16. A pharmaceutical composition, comprising a purified bacterial mixture of at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa,
wherein the bacterial mixture induces proliferation and/or accumulation of regulatory T cells, wherein the bacterial strains are spore forming bacteria and are isolated from a human, and wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
17. The pharmaceutical composition of claim 16 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster IV.
18. The pharmaceutical composition of claim 16 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise two or more strains belonging to Clostridium cluster XIVa.
19. The pharmaceutical composition of claim 16 , wherein the at least two live bacterial strains belonging to Clostridium clusters IV and/or XIVa comprise one or more strains belonging to Clostridium cluster IV and one or more strains belonging to Clostridium cluster XIVa.
20. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition further comprises one or more bacterial strains belonging to a Clostridium cluster other than Clostridium cluster IV or Clostridium cluster XIVa.
21. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
22. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is formulated for oral administration.
23. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is in the form of a capsule.
24. The pharmaceutical composition of claim 16 , wherein the bacteria are in the form of spores.
25. A method of treating a human subject having an autoimmune disease, the method comprising administering the composition of claim 16 .
26. The method of claim 25 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, sprue, rheumatoid arthritis, Type 1 diabetes, graft versus host disease, or multiple sclerosis.
27. A method of treating a human subject having an allergic disease, the method comprising administering the composition of claim 16 .
28. A method of treating a human subject having an infectious disease, the method comprising administering the composition of claim 16 .
29. The method of claim 28 , wherein the infectious disease is Clostridium difficile infection.