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 autism in a subject in need thereof, said subject having autism and a gastrointestinal symptom wherein said gastrointestinal symptom is selected from the group consisting of irritable bowel syndrome, chronic persistent diarrhea, diarrhea, flatulence, constipation, and alternating constipation/diarrhea, and said method comprises administering to said subject an amount of a pharmaceutical composition effective for treating a symptom of said autism, wherein said pharmaceutical composition comprises a viable, non-pathogenic Clostridium sp.; a viable, non-pathogenic Bacteroides sp.; and a viable, non-pathogenic Escherichia coli.
2. The method of claim 1 , wherein said viable, non-pathogenic Clostridium sp. is 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.
3. The method of claim 1 , wherein said viable, non-pathogenic Clostridium sp. is selected from the group consisting of Clostridium bifermentans, Clostridium innocuum, Clostridium ramosum , and Clostridium butyricum.
4. The method of claim 1 , wherein said pharmaceutical composition further comprises an acid suppressant, an antacid, an H2 antagonist, a proton pump inhibitor or a combination thereof.
5. The method of claim 1 , wherein said pharmaceutical composition is formulated as an enteric coated capsule, an enteric coated microcapsule, a powder suitable for reconstitution, a naso-duodenal infusion, or for delivery in the form of an enema or a colonoscopic infusion.
6. The method of claim 1 , wherein said pharmaceutical composition is added to a food, a food additive, a dairy-based product, a soy-based product or a derivative thereof, a jelly, or a yogurt.
7. The method of claim 1 , wherein no existing enteric microflora is removed from said subject prior to administration of said pharmaceutical composition.
8. The method of claim 1 , wherein at least some existing enteric microflora is removed from said subject prior to administration of said pharmaceutical composition.
9. The method of claim 1 , wherein said subject is pretreated with an antibiotic, an acid suppressant, or both prior to administration of said pharmaceutical composition.
10. The method of claim 1 , wherein said pharmaceutical composition is administered three times daily (tid).
11. The method of claim 1 , wherein said subject is pretreated with an orthostatic lavage prior to administration of the pharmaceutical composition.
12. The method of claim 1 , wherein said subject is pretreated with an orthostatic lavage and antibiotic treatment prior to administration of said pharmaceutical composition.
13. The method of claim 1 , wherein said pharmaceutical composition comprises between about 10 9 and about 10 11 viable non-pathogenic bacteria.
14. The method of claim 1 , wherein said pharmaceutical composition comprises no viable Fusobacterium, Propionibacterium, Lactobacillus , anaerobic cocci, Ruminococcus, Gemmiger, Desulfomonas, Peptostreptococcus, Bifidobacterium , or any combination thereof.
15. The method of claim 1 , wherein said pharmaceutical composition further comprises a viable, non-pathogenic colonic bacterium selected from the group consisting of a Collinsella sp., a Fusobacterium sp., a Propionibacterium sp., a Lactobacillus sp., a Ruminococcus sp., a Gemmiger sp., a Desulfomonas sp., a Peptostreptococcus sp., a Bifidobacterium sp., and any combination thereof.
16. The method of claim 1 , wherein said pharmaceutical composition further comprises Peptostreptococcus productus , and wherein said viable, non-pathogenic Clostridium sp. is selected from the group consisting of Clostridium bifermentans, Clostridium innocuum, Clostridium butyricum , and Clostridium ramosum.
17. The method of claim 1 , wherein said pharmaceutical composition comprises a plurality of viable, non-pathogenic Clostridium spores.
18. The method of claim 1 , wherein said pharmaceutical composition is administered orally.
19. The method of claim 1 , wherein said pharmaceutical composition is lyophilized, pulverized, powdered, or any combination thereof.
20. The method of claim 10 , wherein said antibiotic is selected from the group consisting of vancomycin, rifampicin, and nitroimidazole, chloramphenicol, and Septrin.
21. The method of claim 1 , wherein said viable, non-pathogenic Clostridium sp., Bacteroides sp., or Escherichia coli . is from a culture.
22. The method of claim 1 , wherein said Bacteroides sp. is selected from the group consisting of Bacteroides fragilis, Bacteroides thetaiotaomicron , and Bacteroides uniformis.
23. The method of claim 1 , wherein said subject exhibits one or more symptom improvements selected from the group consisting of reduced repetitive action, sleeping through the night, increased eye contact, and progressively increased word power.
24. The method of claim 15 , wherein said viable, non-pathogenic Collinsella sp. is Collinsella aerofaciens.