Probiotic recolonisation therapy
The present invention relates to pharmaceutical compositions suitable for the treatment of chronic diseases associated with the presence of abnormal or an abnormal distribution of microflora in the gastrointestinal tract of a mammalian host, which compositions comprise viable non-pathogenic or attenuated pathogenic Clostridia. The compositions further comprise one or more additional viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Bacteroides , Eubacteria, Fusobacteria, Propionibacteria, Lactobacilli, anaerobic cocci, Ruminococcus, E. coli, Gemmiger, Desulfomonas, Peptostreptococcus , and fungi. The present invention also provides pharmaceutical compositions suitable for the treatment of the same chronic diseases comprising viable non-pathogenic or attenuated pathogenic Escherichia coli , at least one strain of viable non-pathogenic or attenuated pathogenic Bacteroides and at least one strain of viable non-pathogenic or attenuated pathogenic microorganism.
1. A pharmaceutical composition in a capsule or microcapsule adapted for enteric delivery comprising a plurality of viable non-pathogenic Clostridium spores and a plurality of viable non-pathogenic microorganisms from one or more genera selected from the group consisting of Coprococcus, Dorea, Eubacterium, Gemmiger , and Ruminococcus , wherein said pharmaceutical composition comprises no viable organisms from at least one genus selected from the group consisting of Lactobacillus and Bifidobacterium.
2. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises no viable organisms from at least one genus selected from the group consisting of Bacteroides, Fusobacterium, Propionibacterium, Lactobacillus, Escherichia, Desulfomonas, Peptostreptococcus , and Bifidobacterium.
3. The pharmaceutical composition of claim 1 , wherein said plurality of viable non-pathogenic microorganisms comprise two or more species selected from the group consisting of Coprococcus catus, Coprococcus comes, Dorea formicigenerans, Eubacterium eligens, Eubacterium hadrum, Eubacterium hallii, Eubacterium rectale, Gemmiger formicilis , and Ruminococcus torques.
4. The pharmaceutical composition of claim 1 , wherein said plurality of viable non-pathogenic microorganisms comprise Coprococcus.
5. The pharmaceutical composition of claim 1 , wherein said plurality of viable non-pathogenic microorganisms comprise Dorea.
6. The pharmaceutical composition of claim 1 , wherein said plurality of viable non-pathogenic microorganisms comprise Eubacterium.
7. The pharmaceutical composition of claim 1 , wherein said plurality of viable non-pathogenic microorganisms comprise Gemmiger.
8. The pharmaceutical composition of claim 1 , wherein said plurality of viable non-pathogenic microorganisms comprise Ruminococcus.
9. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is formulated as an enteric coated capsule or an enteric coated microcapsule.
10. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is frozen.
11. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises about 10 9 to about 10 11 spores or microorganisms.
12. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises about 10 9 to about 10 11 spores.
13. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises about 10 7 to about 10 9 spores or microorganisms.
14. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises about 10 7 to about 10 9 spores.
15. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is lyophilized, pulverized, powdered, or any combination thereof.
16. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is lyophilized.
17. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises no viable Lactobacillus.
18. The pharmaceutical composition of claim 17 , wherein said pharmaceutical composition comprises no viable Bifidobacterium.
19. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises no viable Bacteroides.
20. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition consists essentially of spores.
21. The pharmaceutical composition of claim 1 , wherein said Clostridium spores are selected from the group consisting of Clostridium absonum, Clostridium argentinense, Clostridium baratii, Clostridium bifermentans, Clostridium botulinum, Clostridium butyricum, Clostridium cadaveris, Clostridium camis, Clostridium celaturn, Clostridium chauvoei, Clostridium clostridioforme, Clostridium cochlearium, Clostridium difficile, Clostridium fallax, Clostridium felsineum, Clostridium ghonii, Clostridium glycolicum, Clostridium haemolyticum, Clostridium hastiforme, Clostridium histolyticum, Clostridium indolis, Clostridium innocuum, Clostridium irregulare, Clostridium limosum, Clostridium malenominatum, Clostridium novyi, Clostridium oroticum, Clostridium paraputrificum, Clostridium perfringens, Clostridium piliforme, Clostridium putrefaciens, Clostridium putrificum, Clostridium ramosum, Clostridium sardiniense, Clostridium sartagoforme, Clostridium scindens, Clostridium septicum, Clostridium sordeffii, Clostridium sphenoides, Clostridium spiroforme, Clostridium sporogenes, Clostridium subterminale, Clostridium symbiosum, Clostridium tertium, Clostridium tetani, Clostridium welchii , and Clostridium villosum.
22. The pharmaceutical composition of claim 1 , wherein said plurality of viable non-pathogenic microorganisms comprise Coprococcus, Dorea, Eubacterium, Gemmiger , and Ruminococcus.
23. A pharmaceutical composition in a capsule or microcapsule adapted for enteric delivery comprising a plurality of viable non-pathogenic Clostridium spores and a plurality of viable non-pathogenic microorganisms from one or more genera selected from the group consisting of Gemmiger and Ruminococcus , wherein said pharmaceutical composition does not comprise viable organisms from at least one genus selected from the group consisting of Lactobacillus and Bifidobacterium.
24. The pharmaceutical composition of claim 23 , wherein said plurality of viable non-pathogenic microorganisms comprise both Gemmiger and Ruminococcus.
25. The pharmaceutical composition of claim 23 , wherein said plurality of viable non-pathogenic microorganisms comprise Gemmiger formicilis and Ruminococcus torques.
26. The pharmaceutical composition of claim 23 , wherein said Clostridium spores are selected from the group consisting of Clostridium absonum, Clostridium argentinense, Clostridium baratii, Clostridium bifermentans, Clostridium botulinum, Clostridium butyricum, Clostridium cadaveris, Clostridium camis, Clostridium celaturn, Clostridium chauvoei, Clostridium clostridioforme, Clostridium cochlearium, Clostridium difficile, Clostridium fallax, Clostridium felsineum, Clostridium ghonii, Clostridium glycolicum, Clostridium haemolyticum, Clostridium hastiforme, Clostridium histolyticum, Clostridium indolis, Clostridium innocuum, Clostridium irregulare, Clostridium limosum, Clostridium malenominatum, Clostridium novyi, Clostridium oroticum, Clostridium paraputrificum, Clostridium perfringens, Clostridium piliforme, Clostridium putrefaciens, Clostridium putrificum, Clostridium ramosum, Clostridium sardiniense, Clostridium sartagoforme, Clostridium scindens, Clostridium septicum, Clostridium sordeffii, Clostridium sphenoides, Clostridium spiroforme, Clostridium sporogenes, Clostridium subterminale, Clostridium symbiosum, Clostridium tertium, Clostridium tetani, Clostridium welchii , and Clostridium villosum.
27. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition is formulated as an enteric coated capsule or an enteric coated microcapsule.
28. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition is frozen.
29. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition comprises about 10 9 to about 10 11 spores or microorganisms.
30. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition comprises about 10 9 to about 10 11 spores.
31. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition comprises about 10 7 to about 10 9 spores or microorganisms.
32. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition comprises about 10 7 to about 10 9 spores.
33. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition is lyophilized, pulverized, powdered, or any combination thereof.
34. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition does not comprise viable Lactobacillus.
35. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition does not comprise viable Bifidobacterium.
36. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition does not comprise viable Bacteroides.
37. The pharmaceutical composition of claim 23 , wherein said pharmaceutical composition consists essentially of spores.