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 composition, comprising a purified bacterial mixture of three 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 strains are spore-forming bacteria and are isolated from a human, and wherein the composition is formulated for delivery to the intestine.
2. The composition of claim 1 , wherein the composition does not include gram negative bacteria.
3. The composition of claim 1 , wherein the composition does not include Bacteroides, Lactobacillus or Bifidobacterium.
4. The composition of claim 1 , wherein the three or more live bacterial strains belonging to Clostridium clusters IV and XIVa comprise two or more strains belonging to Clostridium cluster IV or two or more strains belonging to Clostridium cluster XIVa.
5. The composition of claim 1 , wherein the three or more live bacterial strains belonging to Clostridium clusters IV and XIVa comprise one or more strains belonging to Clostridium cluster IV and one or more strains belonging to Clostridium cluster XIVa.
6. The composition of claim 1 , wherein the bacterial strains include a nucleic acid sequence that can be amplified by a polymerase chain reaction with primers having SEQ ID NO:64 and SEQ ID NO:65.
7. The composition of claim 1 , wherein the bacterial strains include a nucleic acid sequence that can be amplified by a polymerase chain reaction with primers with SEQ ID NO:66 and SEQ ID NO:67.
8. The composition of claim 1 , wherein the bacteria are in the form of spores.
9. The composition of claim 1 , wherein the composition is formulated for oral administration.
10. The composition of claim 1 , wherein the composition further comprises a pharmacologically acceptable carrier.
11. The composition of claim 1 , wherein the composition is in the form of a capsule.
12. The composition of claim 1 , wherein the composition is formulated for delivery to the colon.
13. The composition of claim 1 , wherein the composition further comprises a pH sensitive composition comprising one or more enteric polymers.
14. The composition of claim 1 , wherein the composition further comprises a food product.
15. The composition of claim 1 , wherein the composition comprises four or more bacterial strains.
16. The composition of claim 1 , wherein the composition comprises five or more bacterial strains.
17. The composition of claim 1 , wherein the composition comprises six or more bacterial strains.
18. The composition of claim 1 , wherein the composition comprises seven or more bacterial strains.
19. The composition of claim 1 , wherein the composition comprises eight or more bacterial strains.
20. The composition of claim 1 , wherein the composition comprises nine or more bacterial strains.
21. The composition of claim 1 , wherein the composition comprises ten or more bacterial strains.
22. The composition of claim 1 , wherein the composition comprises eleven or more bacterial strains.
23. The composition of claim 1 , wherein the composition comprises fifteen or more bacterial strains.
24. A method of treating a human subject having an infectious disease, an autoimmune disease or an allergic disease, the method comprising administering the composition of claim 1 .
25. The method of claim 24 , wherein administration results in a higher percentage of Clostridium cluster IV and/or XIVa bacterial species in the intestine of the subject than before the administration of the composition.
26. The method of claim 24 , wherein administration results in an increase in the amount of Clostridium cluster IV and/or XIVa species in the subject as compared to before the administration of the composition.
27. The method of claim 24 , 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 24 , wherein the subject has an infectious disease.
30. The method of claim 29 , wherein the infectious disease is Clostridium difficile infection.