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 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 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 comprises three or more strains.
7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises four or more strains.
8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises five or more strains.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pharmacologically acceptable excipient.
10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration.
11. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in the form of a capsule.
13. A method of treating a human subject having an autoimmune disease, the method comprising administering the composition of claim 1 .
14. The method of claim 13 , 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.
15. A method of treating a human subject having an allergic disease, the method comprising administering the composition of claim 1 .
16. A method of treating a human subject having an infectious disease, the method comprising administering the composition of claim 1 .
17. The method of claim 16 , wherein the infectious disease is Clostridium difficile infection.