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 recolonizing a dysbiotic enteric microflora in a subject in need thereof, which method comprises orally administering to said subject an effective dose of a pharmaceutical composition comprising a viable non-pathogenic or attenuated pathogenic Clostridium , a viable non-pathogenic or attenuated pathogenic Bacteroides , and a viable non-pathogenic or attenuated pathogenic Escherichia coli , wherein said Clostridium, Bacteroides , and Escherichia coli are capable of recolonizing said dysbiotic enteric microflora, and wherein said method does not require the removal of a portion of said subject's existing enteric microflora via orthostatic lavage prior to said oral administration of said pharmaceutical composition.
2. The method of claim 1 , wherein said pharmaceutical composition does not comprise one or more viable microorganisms selected from the group consisting of Eubacterium, Lactobacillus , and Bifidobacterium.
3. The method of claim 1 , wherein said dysbiotic enteric microflora is caused by a Clostridium difficile infection.
4. The method of claim 1 , wherein said subject is in need of treatment for a gastrointestinal symptom selected from the group consisting of irritable bowel syndrome, chronic persistent diarrhoea, diarrhoea, flatulence, constipation, and alternating constipation/diarrhoea.
5. The method of claim 1 , wherein said pharmaceutical composition is administered for a period of time sufficient to displace said subject's existing enteric microflora.
6. The method of claim 1 , wherein said pharmaceutical composition is administered once, twice, or three times daily.
7. The method of claim 1 , wherein said pharmaceutical composition is in a capsule or microcapsule adapted for enteric delivery.
8. The method of claim 1 , wherein said pharmaceutical composition is lyophilized.
9. The method of claim 1 , wherein said pharmaceutical composition comprises no antibiotic resistant populations.
10. The method of claim 1 , wherein said effective dose comprises between about 10 5 and about 10 11 viable microbes, between about 10 7 and about 10 9 viable microbes, or between about 10 9 and about 10 11 viable microbes.
11. The method of claim 1 , wherein said viable non-pathogenic or attenuated pathogenic Clostridium comprises a species selected from the group consisting of Clostridium absonum, Clostridium argentinense, Clostridium baratii, Clostridium bifermentans, Clostridium botulinum, Clostridium butyricum, Clostridium cadaveris, Clostridium camis, Clostridium celatum, 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 sordellii, Clostridium sphenoides, Clostridium spiroforme, Clostridium sporogenes, Clostridium subterminale, Clostridium symbiosum, Clostridium tertium, Clostridium tetani, Clostridium welchii , and Clostridium villosum.
12. The method of claim 1 , wherein said pharmaceutical composition comprises at least two species selected from the group consisting of Clostridium bifermentans, Clostridium innocuum, Clostridium ramosum , and Clostridium butyricum.
13. The method of claim 1 , wherein said viable non-pathogenic or attenuated pathogenic Bacteroides comprises a species selected from the group consisting of Bacteroides caccae, Bacteroides coagulans, Bacteroides eggerthii, Bacteroides forsythus, Bacteroides fragilis, Bacteroides gracilis, Bacteroides levil, Bacteroides macacae, Bacteroides merdae, Bacteroides ovatus, Bacteroides pneumosintes, Bacteroides putredinis, Bacteroides pyogenes, Bacteroides stercoris, Bacteroides tectum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus , and Bacteroides vulgatus.
14. A method for treating a disorder associated with the presence of abnormal or an abnormal distribution of gastrointestinal microflora in a subject in need thereof, which method comprises orally administering to said subject an effective amount of a pharmaceutical composition comprising a viable non-pathogenic or attenuated pathogenic Clostridium , a viable non-pathogenic or attenuated pathogenic Bacteroides , and a viable non-pathogenic or attenuated pathogenic E. coli , wherein said Clostridium, Bacteroides , and Escherichia coli are capable of treating said disorder, and wherein said method does not require the removal of a portion of said subject's existing enteric microflora via orthostatic lavage prior to said oral administration of said pharmaceutical composition.
15. The method of claim 14 , wherein said method achieves continuing symptom improvement.
16. A method for treating a gastrointestinal disorder in a subject in need thereof, which method comprises orally administering to said subject an effective amount of a pharmaceutical composition comprising a viable non-pathogenic or attenuated pathogenic Clostridium , a viable non-pathogenic or attenuated pathogenic Bacteroides , and a viable non-pathogenic or attenuated pathogenic E. coli , wherein said Clostridium, Bacteroides , and Escherichia coli are capable of treating said gastrointestinal disorder, and wherein said method does not require the removal of a portion of said subject's existing enteric microflora via orthostatic lavage prior to said oral administration of said pharmaceutical composition.
17. The method of claim 16 , wherein said gastrointestinal disorder is selected from the group consisting of a chronic Clostridium difficile infection, ulcerative colitis, Crohn's disease, and irritable bowel syndrome.
18. The method of claim 16 , wherein said gastrointestinal disorder is a chronic Clostridium difficile infection.
19. The method of claim 16 , wherein said gastrointestinal disorder is ulcerative colitis.
20. The method of claim 16 , wherein said gastrointestinal disorder is Crohn's disease.
21. The method of claim 16 , wherein said gastrointestinal disorder is irritable bowel syndrome.