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 six or more 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, and wherein the pharmaceutical composition is formulated for delivery to the intestine.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises seven or more bacterial strains.
3. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises eight or more bacterial strains.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises nine or more bacterial strains.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises ten or more bacterial strains.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises eleven or more bacterial strains.
7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises twelve or more bacterial strains.
8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises thirteen or more bacterial strains.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises fourteen or more bacterial strains.
10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises fifteen or more bacterial strains.
11. 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 cluster XIVa.
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration.
13. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in the form of a capsule.
15. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
16. 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 .
17. The method of claim 16 , wherein the human subject has an autoimmune disease.
18. The method of claim 17 , 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.
19. The method of claim 16 , wherein the subject has an infectious disease, and wherein the infectious disease is Clostridium difficile infection.
20. The method of claim 16 , wherein the subject has an allergic disease.
21. 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 pharmaceutical composition further comprises two or more bacterial strains belonging to a Clostridium cluster other than Clostridium cluster IV or cluster XIVa.
22. The pharmaceutical composition of claim 21 , wherein the pharmaceutical composition is formulated for oral administration.
23. The pharmaceutical composition of claim 21 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
24. The pharmaceutical composition of claim 21 , wherein the pharmaceutical composition is in the form of a capsule.
25. The pharmaceutical composition of claim 21 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
26. 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 21 .
27. The method of claim 26 , wherein the human subject has an autoimmune disease.
28. The method of claim 27 , 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.
29. The method of claim 26 , wherein the subject has an infectious disease, and wherein the infectious disease is Clostridium difficile infection.
30. The method of claim 26 , wherein the subject has an allergic disease.