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 method for treating a gastrointestinal disorder in a subject in need thereof, said method comprising orally administering to said subject an amount of a pharmaceutical composition effective for treating said gastrointestinal disorder, wherein said pharmaceutical composition comprises non-pathogenic Clostridium and one or more genera selected from the group consisting of Collinsella, Coprococcus, Eubacterium , and Ruminococcus , wherein said pharmaceutical composition does not comprise Lactobacillus, Bifidobacterium , or both, and wherein said gastrointestinal disorder is selected from the group consisting of Clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome, chronic persistent diarrhoea, diarrhoea, flatulence, constipation, and alternating constipation/diarrhoea, wherein said pharmaceutical composition comprises about 10 7 to about 10 9 or about 10 9 to about 10 11 microorganisms.
2. A method for treating a gastrointestinal disorder in a subject in need thereof, said method comprising administering to said subject orally an amount of a pharmaceutical composition comprising donor-derived microflora effective for treating said gastrointestinal disorder, wherein said donor-derived microflora comprises non-pathogenic Clostridium and does not comprise Lactobacillus, Bifidobacterium or both, and wherein said gastrointestinal disorder is selected from the group consisting of Clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome, chronic persistent diarrhoea, diarrhoea, flatulence, constipation, and alternating constipation/diarrhoea, wherein said pharmaceutical composition comprises about 10 7 to about 10 9 or about 10 9 to about 10 11 microorganisms.
3. The method of claim 2 , wherein said pharmaceutical composition comprises Clostridium spores.
4. The method of claim 2 , wherein said pharmaceutical composition comprises Clostridium, Bacteroides , and Escherichia coli.
5. The method of claim 2 , wherein said pharmaceutical composition comprises Clostridium and Collinsella.
6. The method of claim 2 , wherein said pharmaceutical composition further comprises one or more genera selected from the group consisting of Collinsella, Coprococcus, Eubacterium , and Ruminococcus.
7. The method of claim 2 , wherein said donor-derived microflora is lyophilized, pulverized, powdered, or any combination thereof, or wherein said pharmaceutical composition is formulated as an enteric coated capsule or an enteric coated microcapsule.
8. The method of claim 2 , wherein said pharmaceutical composition is in a food, a food additive, a dairy-based product, a soy-based product or a derivative thereof, a jelly or a yogurt.
9. The method of claim 2 , wherein said gastrointestinal disorder is a Clostridium difficile infection.
10. The method of claim 9 , wherein said Clostridium difficile infection is a chronic Clostridium difficile infection.
11. The method of claim 2 , wherein said gastrointestinal disorder is selected from the group consisting of irritable bowel syndrome, chronic persistent diarrhoea, diarrhoea, flatulence, constipation, and alternating constipation/diarrhoea.
12. The method of claim 2 , wherein said subject further exhibits autistic symptoms, and wherein said method improves said autistic symptoms.
13. The method of claim 2 , wherein said method comprises an initial treatment dose and a subsequent maintenance dose.
14. The method of claim 2 , wherein said pharmaceutical composition comprises about 10 9 to about 10 11 microorganisms.
15. The method of claim 2 , wherein said pharmaceutical composition consists essentially of spores.
16. The method of claim 2 , further comprising administering to said subject an antibiotic, an acid suppressant, an antacid, an H2 antagonist, a proton pump inhibitor or a combination thereof.
17. The method of claim 9 , wherein said donor-derived microflora consists essentially of a selected group of fecal bacteria.
18. The method of claim 9 , wherein said donor-derived microflora consists essentially of fecal spores.
19. The method of claim 9 , wherein said pharmaceutical composition further comprises one or more general selected from the group consisting of Coprococcus, Eubacterium , and Ruminococcus.
20. The method of claim 1 , wherein said gastrointestinal disorder is Clostridium difficile infection.
21. The method of claim 20 , wherein said Clostridium difficile infection is chronic Clostridium difficile infection.
22. The method of claim 20 , wherein said pharmaceutical composition comprises non-pathogenic Clostridium and non-pathogenic Coprococcus.
23. The method of claim 20 , wherein said pharmaceutical composition comprises non-pathogenic Clostridium and non-pathogenic Dorea.
24. The method of claim 20 , wherein said pharmaceutical composition comprises non-pathogenic Clostridium and non-pathogenic Eubacterium.
25. The method of claim 20 , wherein said pharmaceutical composition comprises non-pathogenic Clostridium and non-pathogenic Ruminococcus.
26. The method of claim 20 , wherein said pharmaceutical composition comprises non-pathogenic Clostridium , non-pathogenic Coprococcus , non-pathogenic Dorea , non-pathogenic Eubacterium , and non-pathogenic Ruminococcus.
27. The method of claim 20 , wherein said pharmaceutical composition comprises non-pathogenic Clostridium , non-pathogenic Gemmiger , and non-pathogenic Ruminococcus.
28. The method of claim 27 , wherein said pharmaceutical composition consists essentially of spores.
29. The method of claim 27 , further comprising administering to said subject an antibiotic.
30. The method of claim 27 , wherein said pharmaceutical composition comprises about 10 9 to about 10 11 microorganisms.
31. The method of claim 20 , wherein said pharmaceutical composition consists essentially of spores.
32. The method of claim 20 , further comprising administering to said subject an antibiotic.
33. The method of claim 20 , wherein said pharmaceutical composition comprises about 10 9 to about 10 11 microorganisms.