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 cells are isolated from a human, wherein the pharmaceutical composition is formulated for delivery to the intestine, and wherein the composition does not include Bacteroides, Lactobacillus , or Bifidobacterium.
2. The pharmaceutical composition of claim 1 , wherein the composition has at least three bacterial strains.
3. The pharmaceutical composition of claim 1 , wherein the composition has at least five bacterial strains.
4. The pharmaceutical composition of claim 1 , wherein the composition has at least 10 bacterial strains.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable carrier.
7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
8. A method of treating a human subject having an infectious disease, an autoimmune disease or an allergic disease, the method comprising administering the pharmaceutical composition of claim 1 .
9. The method of claim 8 , wherein the human subject has an autoimmune disease.
10. The method of claim 9 , 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.
11. The method of claim 8 , wherein the subject has an infectious disease, and wherein the infectious disease is Clostridium difficile infection.
12. A pharmaceutical composition, comprising a purified bacterial mixture of at least three 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 is formulated for delivery to the intestine, and wherein the pharmaceutical composition does not include Bacteroides.
13. The pharmaceutical composition of claim 12 , wherein the composition has at least five bacterial strains.
14. The pharmaceutical composition of claim 12 , wherein the composition has at least 10 bacterial strains.
15. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition does not include Bifidobacterium.
16. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition does not include Lactobacillus.
17. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition is formulated for oral administration.
18. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable carrier.
19. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
20. A method of treating a human subject having an infectious disease, an autoimmune disease or an allergic disease, the method comprising administering the pharmaceutical composition of claim 12 .
21. The method of claim 20 , wherein the human subject has an autoimmune disease.
22. The method of claim 21 , 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.
23. The method of claim 22 , wherein the subject has an infectious disease, and wherein the infectious disease is Clostridium difficile infection.
24. A pharmaceutical composition, comprising a purified bacterial mixture of at least three 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 cells are isolated from a human, wherein the pharmaceutical composition is formulated for delivery to the intestine, and wherein the pharmaceutical composition does not include Lactobacillus.
25. The pharmaceutical composition of claim 24 , wherein the composition has at least five bacterial strains.
26. The pharmaceutical composition of claim 24 , wherein the composition has at least 10 bacterial strains.
27. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition does not include Bifidobacterium.
28. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition is formulated for oral administration.
29. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable carrier.
30. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
31. A method of treating a human subject having an infectious disease, an autoimmune disease or an allergic disease, the method comprising administering the pharmaceutical composition of claim 24 .
32. The method of claim 31 , wherein the human subject has an autoimmune disease.
33. The method of claim 32 , 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.
34. The method of claim 31 , wherein the subject has an infectious disease, and wherein the infectious disease is Clostridium difficile infection.
35. A pharmaceutical composition, comprising a purified bacterial mixture of at least three 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 cells are isolated from a human, wherein the pharmaceutical composition is formulated for delivery to the intestine, and wherein the pharmaceutical composition does not include Bifidobacterium.
36. The pharmaceutical composition of claim 35 , wherein the composition has at least five bacterial strains.
37. The pharmaceutical composition of claim 35 , wherein the composition has at least 10 bacterial strains.
38. The pharmaceutical composition of claim 35 , wherein the pharmaceutical composition is formulated for oral administration.
39. The pharmaceutical composition of claim 35 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable carrier.
40. The pharmaceutical composition of claim 35 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
41. A method of treating a human subject having an infectious disease, an autoimmune disease or an allergic disease, the method comprising administering the pharmaceutical composition of claim 35 .
42. The method of claim 41 , wherein the human subject has an autoimmune disease.
43. The method of claim 42 , 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.
44. The method of claim 41 , wherein the subject has an infectious disease, and wherein the infectious disease is Clostridium difficile infection.