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 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. A method of treating a human subject having an autoimmune disease, the method comprising administering the composition of claim 1 .
11. The method of claim 10 , 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.
12. The method of claim 10 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, or Crohn's disease.
13. A method of treating a human subject having an allergic disease, the method comprising administering the composition of claim 1 .
14. The method of claim 13 , wherein the allergic disease is food allergy.
15. A method of treating a human subject having an infectious disease, the method comprising administering the composition of claim 1 .
16. The method of claim 14 , wherein the infectious disease is Clostridium difficile infection.
17. 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 isolated from a human, and
wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
18. The pharmaceutical composition of claim 17 , 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.
19. The pharmaceutical composition of claim 17 , 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.
20. The pharmaceutical composition of claim 17 , 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.
21. The pharmaceutical composition of claim 17 , 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.
22. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
23. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition is formulated for oral administration.
24. The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition is in the form of a capsule.
25. A method of treating a human subject having an autoimmune disease, the method comprising administering the composition of claim 17 .
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. The method of claim 25 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, or Crohn's disease.
28. A method of treating a human subject having an allergic disease, the method comprising administering the composition of claim 17 .
29. The method of claim 28 , wherein the allergic disease is food allergy.
30. A method of treating a human subject having an infectious disease, the method comprising administering the composition of claim 17 .
31. The method of claim 30 , wherein the infectious disease is Clostridium difficile infection.
32. 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 human commensal bacteria, and
wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
33. The pharmaceutical composition of claim 32 , 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.
34. The pharmaceutical composition of claim 32 , 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.
35. The pharmaceutical composition of claim 32 , 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.
36. The pharmaceutical composition of claim 32 , 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.
37. The pharmaceutical composition of claim 32 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
38. The pharmaceutical composition of claim 32 , wherein the pharmaceutical composition is formulated for oral administration.
39. The pharmaceutical composition of claim 32 , wherein the pharmaceutical composition is in the form of a capsule.
40. A method of treating a human subject having an autoimmune disease, the method comprising administering the composition of claim 32 .
41. The method of claim 40 , 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.
42. The method of claim 40 , wherein the autoimmune disease is organ transplant rejection, inflammatory bowel disease (IBD), ulcerative colitis, or Crohn's disease.
43. A method of treating a human subject having an allergic disease, the method comprising administering the composition of claim 32 .
44. The method of claim 43 , wherein the allergic disease is food allergy.
45. A method of treating a human subject having an infectious disease, the method comprising administering the composition of claim 32 .
46. The method of claim 45 , wherein the infectious disease is Clostridium difficile infection.