Probiotic recolonisation therapy

Abstract

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 useful for the treatment and/or prophylaxis of chronic disorders associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora, which composition comprises viable non-pathogenic or attenuated pathogenic Clostridia. 
     
     
         2 . A composition according to  claim 1 , wherein the Clostridia is selected from the group consisting of  Clostridium absonum, Clostridium argentinense, Clostridium baratii, Clostridium bifermentans, Clostridium botulinum, Clostridium butyricum, Clostridium cadaveris, Clostridium carnis, 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, Clostridium villosum.    
     
     
         3 . A composition according to either  claim 1  or  claim 2 , wherein the composition further comprises at least one strain of viable non-pathogenic or attenuated pathogenic  Bacteroides.    
     
     
         4 . A composition according to  claim 3 , wherein said  Bacteroides  is selected from the group consisting of  Bacteroides caccae, Bacteroides capillosus, Bacteroides coagulans, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides forsythus, Bacteroides fragilis, Bacteroides fragilis - ryhmä, Bacteroides gracilis, Bacteroides levii, Bacteroides macacae, Bacteroides merdae, Bacteroides ovatus, Bacteroides pneumosintes, Bacteroides putredinis, Bacteroides pyogenes, Bacteroides splanchnicus, Bacteroides stercoris, Bacteroides tectum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus.    
     
     
         5 . A composition according to any one of  claims 1  to  3 , wherein the composition further comprises 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         6 . A composition according to  claim 5 , wherein the one or more additional viable non-pathogenic or attenuated pathogenic microorganisms are  Bacteroides fragilis  ss.  Vulgatus, Eubacterium aerofaciens, Bacteroides fragilis  ss.  Thetaiotaomicron, Peptostreptococcus productus II, Bacteroides fragilis  ss.  Distasonis, Fusobacterium prausnitzii, Coprococcus eutactus, Eubacterium aerofaciens  III,  Peptostreptococcus productus  I,  Ruminococcus bronii, Bifidobacterium adolescentis, Gemmiger formicilis, Bifidobacterium longum, Eubacterium siraeum, Ruminococcus torques, Eubacterium rectale  III-H,  Eubacterium rectale  IV,  Eubacterium eligens, Bacteroides eggerthii, Clostridium leptum, Bacteroides fragilis  ss. A,  Eubacterium biforme, Bifidobacterium infantis, Eubacterium rectale  III-F,  Coprococcus comes, Bacteroides capillosus, Ruminococcus albus, Eubacterium formicigenerans, Eubacterium haffii, Eubacterium ventriosum  I,  Fusobacterium russii, Ruminococcus obeum, Eubacterium rectale  II,  Clostridium ramosum  I,  Lactobacillus leichmanii, Ruminococcus cailidus, Butyrivibrio crossotus, Acidaminococcus fermentans, Eubacterium ventriosum, Bacteroides fragilis  ss.  fragilis, Bacteroides  AR,  Coprococcus catus, Eubacterium hadrum, Eubacterium cylindroides, Eubacterium ruminantium, Eubacterium  CH-1,  Staphylococcus epidermidis, Peptostreptococcus  BL,  Eubacterium limosum, Bacteroides praeacutus, Bacteroides  L,  Fusobacterium mortiferum I, Fusobacterium naviforme, Clostridium innocuum, Clostridium ramosum, Propionibacterium acnes, Ruminococcus flavefaciens, Ruminococcus  AT,  Peptococcus  AU-1,  Eubacterium  AG, -AK, -AL, -AL-1, -AN;  Bacteroides fragilis  ss.  ovatus , -ss. d, -ss. f;  Bacteroides  L-1, L-5;  Fusobacterium nucleatum, Fusobacterium mortiferum, Escherichia coli, Streptococcus morbillorum, Peptococcus magnus, Peptococcus  G, -AU-2;  Streptococcus intermedius, Ruminococcus lactaris, Ruminococcus  CO  Gemmiger  X,  Coprococcus  BH, —CC;  Eubacterium tenue, Eubacterium ramulus, Eubacterium  AE, -AG-H, -AG-M, -AJ, -BN-1;  Bacteroides clostridiiformis  ss.  clostridliformis, Bacteroides coagulans, Bacteroides orails, Bacteroides ruminicola  ss.  brevis , -ss.  ruminicola, Bacteroides splanchnicus, Desuifomonas pigra, Bacteroides  L-4, -N-i;  Fusobacterium  H,  Lactobacillus  G, or  Succinivibrio  A. 
     
     
         7 . A composition according to any one of  claims 1  to  6 , wherein the composition further comprises fungi. 
     
     
         8 . A composition according to  claim 7 , wherein the fungi are  Monilia.    
     
     
         9 . A composition according to any one of  claims 1  to  8 , wherein the composition further comprises at least one strain of viable non-pathogenic or attenuated pathogenic  Bifidobacterium.    
     
     
         10 . A pharmaceutical composition useful for the treatment and/or prophylaxis of chronic disorders associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora, which composition comprises viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Clostridia,  Bacteroides, Peptostreptococcus, Escherichia coli, Bifidobacterium , and  Lactobacillus.    
     
     
         11 . A composition according to  claim 10 , wherein the composition further comprises 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         12 . A pharmaceutical composition useful for the treatment and/or prophylaxis of chronic disorders associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora, which composition comprises viable non-pathogenic or attenuated pathogenic  Escherichia coli , at least one strain of viable non-pathogenic or attenuated pathogenic  Bacteroides  and at least one other viable non-pathogenic or attenuated pathogenic microorganism. 
     
     
         13 . A composition according to  claim 10 , wherein the  Bacteroides  is selected form the group consisting of  Bacteroides caccae, Bacteroides capillosus, Bacteroides coagulans, Bacteroides distasonis Bacteroides eggerthii, Bacteroides forsythus, Bacteroides fragilis, Bacteroides fragilis - ryhmä, Bacteroides gracilis, Bacteroides levii, Bacteroides macacae, Bacteroides merdae, Bacteroides ovatus, Bacteroides pneumosintes, Bacteroides putredinis, Bacteroides pyogenes, Bacteroides splanchnicus, Bacteroides stercoris, Bacteroides tectum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus.    
     
     
         14 . A composition according to  claim 12  or  claim 13 , wherein the composition further comprises 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         15 . A composition according to any one of  claims 12  to  14 , wherein the other viable non-pathogenic or attenuated pathogenic microorganism is selected from the group consisting of Clostridia,  Peptostreptococcus, Bifidobacterium , and  Lactobacillus.    
     
     
         16 . A composition according to any one of  claims 1  to  15 , further comprising an acid suppressant. 
     
     
         17 . A composition according to any one of  claims 1  to  16 , further comprising an antacid. 
     
     
         18 . A composition according to any one of  claims 1  to  17 , further comprising an H2 antagonist. 
     
     
         19 . A composition according to any one of  claims 1  to  18 , further comprising a proton pump inhibitor. 
     
     
         20 . A composition according to any one of  claims 1  to  19 , wherein said microorganisms are spores. 
     
     
         21 . A composition according to any one of  claims 1  to  19 , wherein the composition is lyophilised, pulverised and powdered. 
     
     
         22 . A composition according to any one of  claims 1  to  19 , wherein the composition is a liquid culture. 
     
     
         23 . A composition according to any one of  claims 1  to  22 , in the form of an enteric coated capsule, an enteric coated microcapsule, or a powder suitable for reconstitution. 
     
     
         24 . A composition according to any one of  claims 1  to  23 , presented in the form of an enema. 
     
     
         25 . A composition according to any one of  claims 1  to  23 , in the form of a food additive. 
     
     
         26 . A composition according to  claim 25 , wherein said food is a dairy-based product, a soy-based product, or a derivative thereof. 
     
     
         27 . A composition according to either  claim 25  or  claim 26 , wherein said food is yogurt. 
     
     
         28 . A food or food supplement containing a composition according to any one of  claims 1  to  23 . 
     
     
         29 . A method for the treatment and/or prophylaxis of a chronic disorder associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora, which method comprises administering an effective amount of a composition comprising viable non-pathogenic or attenuated pathogenic Clostridia for a period of time sufficient to displace the existing microflora. 
     
     
         30 . The method of  claim 29 , wherein the Clostridia is selected from the group consisting of  Clostridium absonum, Clostridium argentinense, Clostridium baratii, Clostridium bifermentans, Clostridium botulinum, Clostridium butyricum, Clostridium cadaveris, Clostridium carnis, 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, Clostridium villosum.    
     
     
         31 . The method of either  claim 29  or  claim 30 , further comprising administering at least one strain of viable non-pathogenic or attenuated pathogenic  Bacteroides.    
     
     
         32 . The method of  claim 31 , wherein said  Bacteroides  is selected from the group consisting of  Bacteroides caccae, Bacteroides capillosus, Bacteroides coagulans, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides forsythus, Bacteroides fragilis, Bacteroides fragilis - ryhmä, Bacteroides gracilis, Bacteroides levii, Bacteroides macacae, Bacteroides merdae, Bacteroides ovatus, Bacteroides pneumosintes, Bacteroides putredinis, Bacteroides pyogenes, Bacteroides splanchnicus, Bacteroides stercoris, Bacteroides tectum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus.    
     
     
         33 . A method according to any one of  claims 29  to  32 , further comprising administering 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         34 . A method according to  claim 33  wherein the one or more additional viable non-pathogenic or attenuated pathogenic microorganisms are  Bacteroides fragilis  ss.  Vulgatus, Eubacterium aerofaciens, Bacteroides fragilis  ss.  Thetaiotaomicron, Peptostreptococcus productus  II,  Bacteroides fragilis  ss.  Distasonis, Fusobacterium prausnitzii, Coprococcus eutactus, Eubacterium aerofaciens  III,  Peptostreptococcus productus  I,  Ruminococcus bronii, Bifidobacterium adolescentis, Gemmiger formicilis, Bifidobacterium longum, Eubacterium siraeum, Ruminococcus torques, Eubacterium rectale  III-H,  Eubacterium rectale  IV,  Eubacterium eligens, Bacteroides eggerthii, Clostridium leptum, Bacteroides fragilis  ss. A,  Eubacterium biforme, Bifidobacterium infantis, Eubacterium rectale  III-F,  Coprococcus comes, Bacteroides capillosus, Ruminococcus albus, Eubacterium formicigenerans, Eubacterium hallii, Eubacterium ventriosum  I,  Fusobacterium russii, Ruminococcus obeum, Eubacterium rectale  II,  Clostridium ramosum  I,  Lactobacillus leichmanii, Ruminococcus cailidus, Butyrivibrio crossotus, Acidaminococcus fermentans, Eubacterium ventriosum, Bacteroides fragilis  ss.  fragilis, Bacteroides  AR,  Coprococcus catus, Eubacterium hadrum, Eubacterium cylindroides, Eubacterium ruminantium, Eubacterium  CH-1,  Staphylococcus epidermidis, Peptostreptococcus  BL,  Eubacterium limosum, Bacteroides praeacutus, Bacteroides  L,  Fusobacterium mortiferum  I,  Fusobacterium naviforme, Clostridium innocuum, Clostridium ramosum, Propionibacterium acnes, Ruminococcus flavefaciens, Ruminococcus  AT,  Peptococcus  AU-1,  Eubacterium  AG, -AK, -AL, -AL-1, -AN;  Bacteroides fragilis  ss.  ovatus , -ss. d, -ss. f;  Bacteroides  L-1, L-5;  Fusobacterium nucleatum, Fusobacterium mortiferum, Escherichia coli, Streptococcus morbiliorum, Peptococcus magnus, Peptococcus  G, -AU-2;  Streptococcus intermedius, Ruminococcus  lactaris,  Ruminococcus  CO  Gemmiger  X,  Coprococcus  BH, —CC;  Eubacterium tenue, Eubacterium ramulus, Eubacterium  AE, -AG-H, -AG-M, -AJ, -BN-1;  Bacteroides clostridiiformis  ss.  clostridliformis, Bacteroides coagulans, Bacteroides orails, Bacteroides rumlnicola  ss.  brevis , -ss.  ruminicola, Bacteroides splanchnlcus, Desuifomonas pigra, Bacteroides  L-4, -N-i;  Fusobacterium  H,  Lactobacillus  G, or  Succinivibrio  A. 
     
     
         35 . A method according to any one of  claims 29  to  34 , further comprising administering fungi. 
     
     
         36 . A method according to  claim 35 , wherein the fungi are  Monilia.    
     
     
         37 . The method according to any one of  claims 29  to  36 , further comprising administering at least one strain of viable non-pathogenic or attenuated pathogenic  Bifidobacterium.    
     
     
         38 . A method for the treatment and/or prophylaxis of a chronic disorder associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora, which method comprises administering an effective amount of a composition comprising viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Clostridia,  Bacteroides, Peptostreptococcus, Escherichia coli, Bifidobacterium , and  Lactobacillus  for a period of time sufficient to displace the existing microflora. 
     
     
         39 . A method according to  claim 38 , further comprising administering 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         40 . A method for the treatment and/or prophylaxis of a chronic disorder associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora, which method comprises administering an effective amount of a composition 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 other viable non-pathogenic or attenuated pathogenic microorganism for a period of time sufficient to displace the existing microflora. 
     
     
         41 . The method of  claim 40 , wherein the  Bacteroides  is selected form the group consisting of  Bacteroides caccae, Bacteroides capillosus, Bacteroides coagulans, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides forsythus, Bacteroides. fragilis, Bacteroides fragilis - ryhmä, Bacteroides gracilis, Bacteroides levii, Bacteroides macacae, Bacteroides merdae, Bacteroides ovatus, Bacteroides pneumosintes, Bacteroides putredinis, Bacteroides pyogenes, Bacteroides splanchnicus, Bacteroides stercoris, Bacteroides tectum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus.    
     
     
         42 . A method according to  claim 41 , further comprising administering 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         43 . The method according to any one of  claims 40  to  42 , wherein the other viable non-pathogenic or attenuated pathogenic microorganism is selected from the group consisting of Clostridia,  Peptostreptococcus, Bifidobacterium , and  Lactobacillus.    
     
     
         44 . A method according to any one of  claims 29  to  43 , further comprising administering an acid suppressant. 
     
     
         45 . A method according to any one of  claims 29  to  44 , further comprising administering an antacid. 
     
     
         46 . A method according to any one of  claims 29  to  45 , further comprising administering an H2 antagonist. 
     
     
         47 . A method according to any one of  claims 29  to  46 , further comprising administering a proton pump inhibitor. 
     
     
         48 . The method according to any one of  claims 29  to  47 , wherein said microorganisms are spores. 
     
     
         49 . The method according to any one of  claims 29  to  47 , wherein the composition is lyophilised, pulverised and powdered. 
     
     
         50 . The method according to any one of  claims 29  to  47 , wherein the composition is a liquid culture. 
     
     
         51 . The method according to any one of  claims 29  to  50 , wherein the composition is administered in the form of an enteric coated capsule, an enteric coated microcapsule, or a reconstituted powder. 
     
     
         52 . A method according to any one of  claims 29  to  51 , wherein the composition is administered in the form of an enema. 
     
     
         53 . The method according to any one of  claims 29  to  51 , wherein the composition is administered in the form of a food or drink. 
     
     
         54 . The method according to  claim 53 , wherein said food is a dairy-based product, a soy-based product, or a derivative thereof. 
     
     
         55 . The method according to either  claim 53  or  claim 54 , wherein said food is yogurt. 
     
     
         56 . The method according to any one of  claims 29  to  55 , wherein the period of time sufficient to displace the existing microflora is several days to several weeks. 
     
     
         57 . The method according to any one of  claims 29  to  56 , wherein the mammalian host is human. 
     
     
         58 . The method according to any one of  claims 29  to  57 , further comprising administration of an effective amount of at least one antibiotic prior to administering said composition. 
     
     
         59 . The method according to  claim 58 , wherein said antibiotic is an anti-Clostridial antibiotic. 
     
     
         60 . The method according to  claim 59 , wherein said anti-Clostridial antibiotic is selected from the group consisting of vancomycin, rifampicin, and nitroimidazole. 
     
     
         61 . The method according to any one of  claims 29  to  60 , further comprising nasogastric and/or nasoduodenal washout prior to administering said composition. 
     
     
         62 . The method according to any one of  claims 29  to  60 , wherein the composition is administered by ingestion or by parenteral infusion. 
     
     
         63 . The method according to any one of  claims 29  to  60 , wherein administration is by enema, per-colonoscope, by intubation of the small bowel or orally. 
     
     
         64 . The method according to any one of  claims 29  to  63 , wherein the chronic disorder is a gastrointestinal disorder, a rheumatic disorder, an immune mediated disorder, an auto-immune disorder, a neurological disorder, a regressive disorder, a liver disorder, a psychiatric disorder or a dermatological condition. 
     
     
         65 . The method of  claim 64 , wherein said gastrointestinal disorder is irritable bowel syndrome or spastic colon. 
     
     
         66 . The method of  claim 64 , wherein said gastrointestinal disorder is functional bowel disease (FBD), inflammatory bowel disease, chronic gut infection, or a viral gastrointestinal disorder. 
     
     
         67 . The method of  claim 66 , wherein said functional bowel disease is constipation predominant FBD, pain predominant FBD, upper abdominal FBD (non ulcer dyspepsia), or gastro oesophageal reflux. 
     
     
         68 . The method of  claim 66 , wherein said inflammatory bowel disease is Crohn's disease, ulcerative colitis, indeterminate colitis, collagenous colitis, microscopic colitis, chronic  Clostridium difficile  infection, pseudomembranous colitis, mucous colitis, antibiotic associated colitis, idiopathic or simple constipation, diverticular disease, AIDS enteropathy, small bowel bacterial overgrowth, coeliac disease, polyposis  coli , colonic polyps, or chronic idiopathic pseudo obstructive syndrome. 
     
     
         69 . The method of  claim 66 , wherein said chronic gut infection is a bacterial, viral, fungal or protozoal infection. 
     
     
         70 . The method of  claim 66 , wherein said viral gastrointestinal disorder is viral gastroenteritis, Norwalk viral gastroenteritis, rotavirus gastroenteritis, AIDS related gastroenteritis. 
     
     
         71 . The method of  claim 64 , wherein said rheumatic disorder is rheumatoid arthritis, non-rheumatoid arthritidies, non rheumatoid factor positive arthritis, ankylosing spondylitis, Reiter's syndrome, or Lyme Disease. 
     
     
         72 . The method of  claim 64 , wherein said immune mediated disorder is glomerulonephritis, haemolytic uraemic syndrome, juvenile diabetes mellitus, mixed cryoglobulinaemia, polyarteritis, familial Mediterranean fever, amyloidosis, scleroderma, systemic lupus erythematosus, or Behcets syndrome. 
     
     
         73 . The method of  claim 64 , wherein said auto-immune disorder is systemic Lupus, idiopathic thrombocytopenic purpura, Sjogren's syndrome, haemolytic uraemic syndrome, or scleroderma. 
     
     
         74 . The method of  claim 64 , wherein said neurological disorder is chronic fatigue syndrome, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Guillain Barre syndrome, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), migraine or myasthenia gravis. 
     
     
         75 . The method of  claim 64 , wherein said regressive disorder is Aspergers syndrome, Rett syndrome, attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD). 
     
     
         76 . The method of  claim 64 , wherein said regressive disorder is autism. 
     
     
         77 . The method of  claim 64 , wherein said disorder is sudden infant death syndrome (SIDS) or anorexia nervosa. 
     
     
         78 . The method of  claim 64 , wherein said liver disorder is primary biliary cirrhosis, primary sclerosing cholangitis, fatty liver or cryptogenic cirrhosis. 
     
     
         79 . The method of  claim 64 , wherein said psychiatric disorder is chronic depression, schizophrenia/psychotic disorders, or manic depressive illness. 
     
     
         80 . The method of  claim 64 , wherein said dermatological condition is chronic urticaria, acne, dermatitis herpetiformis or a vasculitic disorder. 
     
     
         81 . The method according to any one of  claims 29  to  80 , wherein each dose is at least about 10 3  cells. 
     
     
         82 . The method according to any one of  claims 29  to  80 , wherein each dose is in the range of about 10 3  cells to about 10 13  cells. 
     
     
         83 . The method according to any one of  claims 29  to  80 , wherein each dose is in the range of about 10 5  cells to about 10 11  cells. 
     
     
         84 . The method according to any one of  claims 29  to  80 , wherein each dose is in the range of about 10 7  cells to about 10 9  cells. 
     
     
         85 . The method according to any one of  claims 29  to  84 , further comprising an initial treatment regimen of about 10 10  cells per dose administered 3 to 6 times per day for a period sufficient to stabilise the gut flora. 
     
     
         86 . The method according to  claim 85 , wherein the period sufficient to stabilise the gut flora is about 7 to about 10 days. 
     
     
         87 . A method for the treatment and/or prophylaxis of a chronic disorder associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora, which method comprises administering an effective amount of a composition according to any one of  claims 1  to  28  for a period of time sufficient to displace the existing microflora. 
     
     
         88 . A method according to  claim 87 , further comprising administering an acid suppressant. 
     
     
         89 . A method according to  claim 87  or  claim 88 , further comprising administering an antacid. 
     
     
         90 . A method according to any one of  claims 87  to  89 , further comprising administering an H2 antagonist. 
     
     
         91 . A method according to any one of  claims 87  to  90 , further comprising administering a proton pump inhibitor. 
     
     
         92 . The method according to any one of  claims 87  to  91 , wherein said microorganisms are spores. 
     
     
         93 . The method according to any one of  claims 87  to  91 , wherein the composition is lyophilised, pulverised and powdered. 
     
     
         94 . The method according to any one of  claims 87  to  91 , wherein the composition is a liquid culture. 
     
     
         95 . The method according to any one of  claims 87  to  94 , wherein the composition is administered in the form of an enteric coated capsule, an enteric coated microcapsule, or a reconstituted powder. 
     
     
         96 . A method according to any one of  claims 87  to  95 , wherein the composition is administered in the form of an enema. 
     
     
         97 . The method according to any one of  claims 87  to  95 , wherein the composition is administered in the form of a food or drink. 
     
     
         98 . The method according to  claim 97 , wherein said food is a dairy-based product, a soy-based product, or a derivative thereof. 
     
     
         99 . The method according to either  claim 97  or  claim 98 , wherein said food is yogurt. 
     
     
         100 . The method according to any one of  claims 87  to  99 , wherein the period of time sufficient to displace the existing microflora is several days to several weeks. 
     
     
         101 . The method according to any one of  claims 87  to  100 , wherein the mammalian host is human. 
     
     
         102 . The method according to any one of  claims 87  to  101 , further comprising administration of an effective amount of at least one antibiotic prior to administering said composition. 
     
     
         103 . The method according to  claim 102 , wherein said antibiotic is an anti-Clostridial antibiotic. 
     
     
         104 . The method according to  claim 103 , wherein said anti-Clostridial antibiotic is selected from the group consisting of vancomycin, rifampicin, and nitroimidazole. 
     
     
         105 . The method according to any one of  claims 87  to  104 , further comprising nasogastric and/or nasoduodenal washout prior to administering said composition. 
     
     
         106 . The method according to any one of  claims 87  to  104 , wherein the composition is administered by ingestion or by parenteral infusion. 
     
     
         107 . The method according to any one of  claims 87  to  104 , wherein administration is by enema, per-colonoscope, by intubation of the small bowel or orally. 
     
     
         108 . The method according to any one of  claims 87  to  107 , wherein the chronic disorder is a gastrointestinal disorder, a rheumatic disorder, an immune mediated disorder, an auto-immune disorder, a neurological disorder, a regressive disorder, a liver disorder, a psychiatric disorder or a dermatological condition. 
     
     
         109 . The method of  claim 108 , wherein said gastrointestinal disorder is irritable bowel syndrome or spastic colon. 
     
     
         110 . The method of  claim 108 , wherein said gastrointestinal disorder is functional bowel disease (FBD), inflammatory bowel disease, chronic gut infection, or a viral gastrointestinal disorder. 
     
     
         111 . The method of  claim 110 , wherein said functional bowel disease is constipation predominant FBD, pain predominant FBD, upper abdominal FBD, non ulcer dyspepsia, or gastro oesophageal reflux. 
     
     
         112 . The method of  claim 110 , wherein said inflammatory bowel disease is Crohn's disease, ulcerative colitis, indeterminate colitis, collagenous colitis, microscopic colitis, chronic  Clostridium difficile  infection, pseudomembranous colitis, mucous colitis, antibiotic associated colitis, idiopathic or simple constipation, diverticular disease, AIDS enteropathy, small bowel bacterial overgrowth, coeliac disease, polyposis  coli , colonic polyps, or chronic idiopathic pseudo obstructive syndrome. 
     
     
         113 . The method of  claim 110 , wherein said chronic gut infection is a bacterial, viral, fungal or protozoal infection. 
     
     
         114 . The method of  claim 110 , wherein said viral gastrointestinal disorder is viral gastroenteritis, Norwalk viral gastroenteritis, rotavirus gastroenteritis, AIDS related gastroenteritis. 
     
     
         115 . The method of  claim 108 , wherein said rheumatic disorder is rheumatoid arthritis, non-rheumatoid arthritidies, non rheumatoid factor positive arthritis, ankylosing spondylitis, Reiter's syndrome, or Lyme Disease. 
     
     
         116 . The method of  claim 108 , wherein said immune mediated disorder is glomerulonephritis, haemolytic uraemic syndrome, juvenile diabetes mellitus, mixed cryoglobulinaemia, polyarteritis, familial Mediterranean fever, amyloidosis, scleroderma, systemic lupus erythematosus, or Behcets syndrome. 
     
     
         117 . The method of  claim 108 , wherein said auto-immune disorder is systemic Lupus, idiopathic thrombocytopenic purpura, Sjogren's syndrome, haemolytic uraemic syndrome, or scleroderma. 
     
     
         118 . The method of  claim 108 , wherein said neurological disorder is chronic fatigue syndrome, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Guillain Barre syndrome, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), migraine or myasthenia gravis. 
     
     
         119 . The method of  claim 108 , wherein said regressive disorder is Aspergers syndrome, Rett syndrome, attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD). 
     
     
         120 . The method of  claim 108 , wherein said regressive disorder is autism. 
     
     
         121 . The method of  claim 108 , wherein said disorder is sudden infant death syndrome (SIDS), anorexia nervosa. 
     
     
         122 . The method of  claim 108 , wherein said liver disorder is primary biliary cirrhosis, primary sclerosing cholangitis, fatty liver or cryptogenic cirrhosis. 
     
     
         123 . The method of  claim 108 , wherein said psychiatric disorder is chronic depression, schizophrenia/psychotic disorders, or manic depressive illness. 
     
     
         124 . The method of  claim 108 , wherein said dermatological condition is chronic urticaria, acne, dermatitis herpetiformis or a vasculitic disorder. 
     
     
         125 . The method according to any one of  claims 87  to  124 , wherein each dose is at least about 10 3  cells. 
     
     
         126 . The method according to any one of  claims 87  to  124 , wherein each dose is in the range of about 10 3  cells to about 10 13  cells. 
     
     
         127 . The method according to any one of  claims 87  to  124 , wherein each dose is in the range of about 10 5  cells to about 10″ cells. 
     
     
         128 . The method according to any one of  claims 87  to  124 , wherein each dose is in the range of about 10 7  cells to about 10 9  cells. 
     
     
         129 . The method according to any one of  claims 87  to  128 , further comprising an initial treatment regimen of about 10 10  cells per dose administered 3 to 6 times per day for a period sufficient to stabilise the gut flora. 
     
     
         130 . The method according to  claim 129 , wherein the period sufficient to stabilise the gut flora is about 7 to about 10 days. 
     
     
         131 . Use of viable non-pathogenic or attenuated pathogenic Clostridia for the manufacture of a medicament for the treatment and/or prophylaxis of a chronic disorder associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora. 
     
     
         132 . The use of  claim 131 , wherein the Clostridia is selected from the group consisting of  Clostridium absonum, Clostridium argentinense, Clostridium baratii, Clostridium bifermentans, Clostridium botulinum, Clostridium butyricum, Clostridium cadaveris, Clostridium carnis, 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 sordeffii, Clostridium sphenoides, Clostridium spiroforme, Clostridium sporogenes, Clostridium subterminale, Clostridium symbiosum, Clostridium tedium, Clostridium tetani, Clostridium welchii, Clostridium villosum.    
     
     
         133 . The use of either  claim 131  or  claim 132 , further comprising at least one strain of viable non-pathogenic or attenuated pathogenic  Bacteroides.    
     
     
         134 . The use of  claim 133 , wherein said  Bacteroides  is selected from the group consisting of  Bacteroides caccae, Bacteroides capillosus, Bacteroides coagulans, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides forsythus, Bacteroides fragilis, Bacteroides fragilis - ryhmä, Bacteroides gracilis, Bacteroides levii, Bacteroides macacae, Bacteroides merdae, Bacteroides ovatus, Bacteroides pneumosintes, Bacteroides putredinis, Bacteroides pyogenes, Bacteroides splanchnicus, Bacteroides stercoris, Bacteroides tectum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus.    
     
     
         135 . The use according to any one of  claims 131  to  134 , further comprising 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         136 . The use according to  claim 135  wherein the one or more additional viable non-pathogenic or attenuated pathogenic microorganisms are  Bacteroides fragilis  ss.  Vulgatus, Eubacterium aerofaciens, Bacteroides fragilis  ss.  Thetaiotaomicron, Peptostreptococcus productus  II,  Bacteroides fragilis  ss.  Distasonis, Fusobacterium prausnitzii, Coprococcus eutactus, Eubacterium aerofaciens  III,  Peptostreptococcus productus  I,  Ruminococcus bronii, Bifidobacterium adolescentis, Gemmiger formicilis, Bifidobacterium longum, Eubacterium siraeum, Ruminococcus torques, Eubacterium rectale  III-H,  Eubacterium rectale  IV,  Eubacterium eligens, Bacteroides eggerthii, Clostridium leptum, Bacteroides fragilis  ss. A,  Eubacterium biforme, Bifidobacterium infantis, Eubacterium rectale  III-F,  Coprococcus comes, Bacteroides capillosus, Ruminococcus albus, Eubacterium formicigenerans, Eubacterium haffii, Eubacterium ventriosum  I,  Fusobacterium russii, Ruminococcus obeum, Eubacterium rectale  II,  Clostridium ramosum  I,  Lactobacillus leichmanii, Ruminococcus cailidus, Butyrivibrio crossotus, Acidaminococcus fermentans, Eubacterium ventriosum, Bacteroides fragilis  ss.  fragilis, Bacteroides  AR,  Coprococcus catus, Eubacterium hadrum, Eubacterium cylindroides, Eubacterium ruminantium, Eubacterium  CH-1,  Staphylococcus epidermidis, Peptostreptococcus  BL,  Eubacterium limosum, Bacteroides praeacutus, Bacteroides  L,  Fusobacterium mortiferum  I,  Fusobacterium naviforme, Clostridium innocuum, Clostridium ramosum, Propionibacterium acnes, Ruminococcus flavefaciens, Ruminococcus  AT,  Peptococcus  AU-1,  Eubacterium  AG, -AK, -AL, -AL-1, -AN;  Bacteroides fragilis  ss.  ovatus , -ss. d, -ss. f;  Bacteroides  L-1, L-5;  Fusobacterium nucleatum, Fusobacterium mortiferum, Escherichia coli, Streptococcus morbiliorum, Peptococcus magnus, Peptococcus  G, -AU-2;  Streptococcus intermedius, Ruminococcus lactaris, Ruminococcus  CO  Gemmiger  X,  Coprococcus  BH, —CC;  Eubacterium tenue, Eubacterium ramulus, Eubacterium  AE, -AG-H, -AG-M, -AJ, -BN-1;  Bacteroides clostridiiformis  ss.  clostridliformis, Bacteroides coagulans, Bacteroides orailis, Bacteroides ruminicola  ss.  brevis , -ss.  ruminicola, Bacteroides splanchnlcus, Desuifomonas pigra, Bacteroides  L-4, -N-i;  Fusobacterium  H,  Lactobacillus  G, or  Succinivibrio  A. 
     
     
         137 . The use according to any one of  claims 131  to  136 , further comprising fungi. 
     
     
         138 . The use according to  claim 137 , wherein the fungi are  Monilia.    
     
     
         139 . The use according to any one of  claims 131  to  138 , further comprising at least one strain of viable non-pathogenic or attenuated pathogenic  Bifidobacterium.    
     
     
         140 . Use of viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Clostridia,  Bacteroides, Peptostreptococcus, Escherichia coli, Bifidobacterium , and  Lactobacillus  for the manufacture of a medicament for the treatment and/or prophylaxis of a chronic disorder associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora. 
     
     
         141 . The use according to  claim 140 , further comprising 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         142 . Use of viable non-pathogenic or attenuated pathogenic  Escherichia coli , at least one strain of viable non-pathogenic or attenuated pathogenic  Bacteroides  and at least one other viable non-pathogenic or attenuated pathogenic microorganism for the manufacture of a medicament for the treatment and/or prophylaxis of a chronic disorder associated with the presence in the gastrointestinal tract of a mammalian host of abnormal or an abnormal distribution of microflora. 
     
     
         143 . The use of  claim 142 , wherein the  Bacteroides  is selected form the group consisting of  Bacteroides caccae, Bacteroides capillosus, Bacteroides coagulans, Bacteroides distasonis, Bacteroides eggerthii, Bacteroides forsythus, Bacteroides. fragilis, Bacteroides fragilis Bacteroides gracilis, Bacteroides levii, Bacteroides macacae, Bacteroides merdae, Bacteroides ovatus, Bacteroides pneumosintes, Bacteroides putredinis, Bacteroides pyogenes, Bacteroides splanchnicus, Bacteroides stercoris, Bacteroides tectum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus.    
     
     
         144 . The use according to  claim 142 , further comprising 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, Escherichia coli, Gemmiger, Desulfomonas, Peptostreptococcus , species. 
     
     
         145 . The use according to any one of  claims 142  to  144 , wherein the other viable non-pathogenic or attenuated pathogenic microorganism is selected from the group consisting of Clostridia,  Peptostreptococcus, Bifidobacterium , and  Lactobacillus.    
     
     
         146 . The use according to any one of  claims 131  to  145 , further comprising an acid suppressant. 
     
     
         147 . The use according to any one of  claims 131  to  146 , further comprising an antacid. 
     
     
         148 . The use according to any one of  claims 131  to  147 , further comprising an H2 antagonist. 
     
     
         149 . The use according to any one of  claims 131  to  148 , further comprising a proton pump inhibitor. 
     
     
         150 . The use according to any one of  claims 131  to  149 , wherein said microorganisms are spores. 
     
     
         151 . The use according to any one of  claims 131  to  150 , wherein the microorganisms are lyophilised, pulverised and powdered. 
     
     
         152 . The use according to any one of  claims 131  to  151 , wherein the microorganism is a liquid culture. 
     
     
         153 . The use according to any one of  claims 131  to  152 , wherein the medicament is an enteric coated capsule, an enteric coated microcapsule, or a reconstituted powder. 
     
     
         154 . The use according to any one of  claims 131  to  153 , wherein the medicament is administered in the form of an enema. 
     
     
         155 . The use according to any one of  claims 131  to  154 , wherein the medicament is administered in the form of a food or drink. 
     
     
         156 . The use according to  claim 155 , wherein said food is a dairy-based product, a soy-based product, or a derivative thereof. 
     
     
         157 . The use according to either  claim 155  or  claim 156 , wherein said food is yogurt. 
     
     
         158 . The use according to any one of  claims 131  to  157 , wherein the treatment and/or prophylaxis period is several days to several weeks. 
     
     
         159 . The use according to any one of  claims 131  to  158 , wherein the mammalian host is human. 
     
     
         160 . The use according to any one of  claims 131  to  159 , wherein the medicament is suitable for administration by ingestion or by parenteral infusion. 
     
     
         161 . The use according to any one of  claims 131  to  159 , wherein the medicament is suitable for administration by enema, per-colonoscope, by intubation of the small bowel or orally. 
     
     
         162 . The use according to any one of  claims 131  to  161 , wherein the chronic disorder is a gastrointestinal disorder, a rheumatic disorder, an immune mediated disorder, an auto-immune disorder, a neurological disorder, a regressive disorder, a liver disorder, a psychiatric disorder or a dermatological condition. 
     
     
         163 . The use of  claim 162 , wherein said gastrointestinal disorder is irritable bowel syndrome or spastic colon. 
     
     
         164 . The use of  claim 163 , wherein said gastrointestinal disorder is functional bowel disease (FBD), inflammatory bowel disease, chronic gut infection, or a viral gastrointestinal disorder. 
     
     
         165 . The use of  claim 164 , wherein said functional bowel disease is constipation predominant FBD, pain predominant FBD, upper abdominal FBD (non ulcer dyspepsia), or gastro oesophageal reflux. 
     
     
         166 . The use of  claim 164 , wherein said inflammatory bowel disease is Crohn's disease, ulcerative colitis, indeterminate colitis, collagenous colitis, microscopic colitis, chronic  Clostridium difficile  infection, pseudomembranous colitis, mucous colitis, antibiotic associated colitis, idiopathic or simple constipation, diverticular disease, AIDS enteropathy, small bowel bacterial overgrowth, coeliac disease, polyposis  coli , colonic polyps, or chronic idiopathic pseudo obstructive syndrome. 
     
     
         167 . The use of  claim 164 , wherein said chronic gut infection is a bacterial, viral, fungal or protozoal infection. 
     
     
         168 . The use of  claim 164 , wherein said viral gastrointestinal disorder is viral gastroenteritis, Norwalk viral gastroenteritis, rotavirus gastroenteritis, AIDS related gastroenteritis. 
     
     
         169 . The use of  claim 162 , wherein said rheumatic disorder is rheumatoid arthritis, non-rheumatoid arthritidies, non rheumatoid factor positive arthritis, ankylosing spondylitis, Reiter's syndrome, or Lyme Disease. 
     
     
         170 . The use of  claim 162 , wherein said immune mediated disorder is glomerulonephritis, haemolytic uraemic syndrome, juvenile diabetes mellitus, mixed cryoglobulinaemia, polyarteritis, familial Mediterranean fever, amyloidosis, scleroderma, systemic lupus erythematosus, or Behcets syndrome. 
     
     
         171 . The use of  claim 162 , wherein said auto-immune disorder is systemic Lupus, idiopathic thrombocytopenic purpura, Sjogren's syndrome, haemolytic uraemic syndrome, or scleroderma. 
     
     
         172 . The use of  claim 162 , wherein said neurological disorder is chronic fatigue syndrome, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Guillain Barre syndrome, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), migraine or myasthenia gravis. 
     
     
         173 . The use of  claim 162 , wherein said regressive disorder is Aspergers syndrome, Rett syndrome, attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD). 
     
     
         174 . The use of  claim 162 , wherein said regressive disorder is autism. 
     
     
         175 . The use of  claim 162 , wherein said disorder is sudden infant death syndrome (SIDS) or anorexia nervosa. 
     
     
         176 . The use of  claim 162 , wherein said liver disorder is primary biliary cirrhosis, primary sclerosing cholangitis, fatty liver or cryptogenic cirrhosis. 
     
     
         177 . The use of  claim 162 , wherein said psychiatric disorder is chronic depression, schizophrenia/psychotic disorders, or manic depressive illness. 
     
     
         178 . The use of  claim 162 , wherein said dermatological condition is chronic urticaria, acne, dermatitis herpetiformis or a vasculitic disorder. 
     
     
         179 . The use according to any one of  claims 131  to  178 , wherein each dose of the medicament is at least about 10 3  cells. 
     
     
         180 . The use according to any one of  claims 131  to  178 , wherein each dose of the medicament is in the range of about 10 3  cells to about 10 13  cells. 
     
     
         181 . The use according to any one of  claims 131  to  178 , wherein each dose of the medicament is in the range of about 10 5  cells to about 10 11  cells. 
     
     
         182 . The use according to any one of  claims 131  to  178 , wherein each dose of the medicament is in the range of about 10 7  cells to about 10 9  cells.