An overview of fecal microbiota transplantation: techniques, indications, and outcomes

      Fecal microbiota transplantation has emerged as a highly effective treatment for recurrent Clostridium difficile infection with very early experience to suggest that it also may play a role in treating other GI and non-GI diseases. Donor screening guidelines are now available along with recommendations regarding routes of administration, diluents, stool weights, and volumes of stool to be used. This review aims to provide an overview of fecal microbiota transplantation, to summarize the data on its efficacy, and to provide the reader with an understanding of how to perform this novel treatment.

      Abbreviations:

      CDI (Clostridium difficile infection), FMT (fecal microbiota transplantation), IBD (inflammatory bowel disease), IBS (irritable bowel syndrome), RCDI (recurrent Clostridium difficile infection)
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      References

        • Grehan M.J.
        • Borody T.J.
        • Leis S.M.
        • et al.
        Durable alteration of the colonic microbiota by the administration of donor fecal flora.
        J Clin Gastroenterol. 2010; 44: 551-561
        • Khoruts A.
        • Dicksved J.
        • Jansson J.K.
        • et al.
        Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea.
        J Clin Gastroenterol. 2010; 44: 354-360
        • Chang J.Y.
        • Antonopoulos D.A.
        • Kalra A.
        • et al.
        Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea.
        J Infect Dis. 2008; 197: 435-438
        • Borody T.J.
        • Warren E.F.
        • Leis S.M.
        • et al.
        Bacteriotherapy using fecal flora: toying with human motions.
        J Clin Gastroenterol. 2004; 38: 475-483
        • Borody T.J.
        • George L.
        • Andrews P.J.
        • et al.
        Bowel flora alteration: a potential cure of inflammatory bowel disease and irritable bowel syndrome?.
        Med J Aust. 1989; 150: 604
      1. Borody TJ, Leis S, McGrath K, et al. Treatment of chronic constipation and colitis using human probiotic infusions: Presented at the Probiotics, Prebiotics and New Foods Conference, Universita Urbaniana, Rome, Italy, September 2-4, 2001.

        • Borody T.J.
        • Warren E.F.
        • Leis S.
        • et al.
        Treatment of ulcerative colitis using fecal bacteriotherapy.
        J Clin Gastroenterol. 2003; 37: 42-47
        • Vrieze A.
        • van Nood E.
        • Holleman F.
        • et al.
        Transfer of intestinal microbiota from lean donors increases insulin sensitivity in subjects with metabolic syndrome.
        Gastroenterology. 2012; 143: 913-916.e7
      2. Anathaswamy A. Faecal transplant eases symptoms of Parkinson’s. New Scientist. Epub 2011 Jan 19.

        • Sekirov I.
        • Russell S.L.
        • Antunes C.M.
        • et al.
        Gut microbiomes in health and disease.
        Physiol Rev. 2010; 90: 859-904
        • Zhang F.
        • Luo W.
        • Shi Y.
        • et al.
        Should we standardize the 1700-year-old fecal microbiota transplantation?.
        Am J Gastroenterol. 2012; 107: 1755
        • Eiseman B.
        • Silen W.
        • Bascom G.S.
        • et al.
        Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis.
        Surgery. 1958; 44: 854-859
        • Schwan A.
        • Sjolin S.
        • Trottestam U.
        • et al.
        Relapsing Clostridium difficile enterocolitis cured by rectal infusion of homologous faeces.
        Lancet. 1983; 2: 845
        • Bakken J.S.
        • Borody T.
        • Brandt L.J.
        • et al.
        Treating Clostridium difficile infection with fecal microbiota transplantation.
        Clin Gastroenterol Hepatol. 2011; 9: 1044-1049
        • Aas J.
        • Gessert C.E.
        • Bakken J.S.
        Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube.
        Clin Infect Dis. 2003; 36: 580-585
        • Lund-Tonnesen S.
        • Berstad A.
        • Schreiner A.
        • et al.
        Clostridium difficile-assosiert diare behandlet med homolog feces.
        Tidsskr Nor Laegeforen. 1998; 118: 1027-1030
        • Persky S.
        • Brandt L.J.
        Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly though a colonoscope.
        Am J Gastroenterol. 2000; 95: 3283-3285
        • Silverman M.S.
        • Davis I.
        • Pillai D.R.
        Success of self-administered home fecal transplantation for chronic Clostridium difficile infection.
        Clin Gastroenterol Hepatol. 2010; 8: 471-473
        • Brandt L.J.
        • Reddy S.S.
        Fecal microbiota transplantation for recurrent Clostridium difficile infection.
        J Clin Gastroenterol. 2011; 45: S159-S167
        • Gough E.
        • Shaikh H.
        • Manges A.R.
        Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection.
        Clin Infect Dis. 2011; 53: 994-1002
        • McDonald L.C.
        • Owings M.
        • Jernigan D.B.
        Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003.
        Emerg Infect Dis. 2006; 12: 409-415
        • Zilberberg M.
        • Shorr A.F.
        • Kollef M.H.
        Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005.
        Emerg Infect Dis. 2008; 14: 929-931
        • O’Brien J.A.
        • Lahue B.J.
        • Caro J.J.
        The emerging infectious challenge of Clostridium difficile infection in adults: 2010 update by the Society of Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).
        Infect Control Hosp Epidemiol. 2010; 31: 431-455
        • Cohen S.H.
        • Gerding D.N.
        • Johnson S.
        • et al.
        Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).
        Infect Control and Hosp Epidemiol. 2010; 31: 431-455
      3. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. Epub 2013 Feb 26.

        • Bakken J.S.
        Fecal bacteriotherapy for recurrent Clostridium difficile infection.
        Anaerobe. 2009; 15: 285-289
        • Huebner E.S.
        • Surawicz C.M.
        Treatment of recurrent Clostridium difficile diarrhea.
        Gastroenterol Hepatol. 2006; 2: 203-208
        • Kyne L.
        • Farrell R.J.
        • Kelly C.P.
        Clostridium difficile.
        Gastroenterol Clin North Am. 2001; 30: 753-777
        • Hamilton M.J.
        • Weingarden A.R.
        • Unno T.
        • et al.
        High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria.
        Gut Microbes. 2013; 4: 125-135
        • van Nood E.
        • Vrieze A.
        • Nieuwdorp M.
        • et al.
        Duodenal infusion of donor feces for recurrent Clostridium difficile.
        N Engl J Med. 2013; 368: 407-415
        • Yoon S.S.
        • Brandt L.J.
        Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy. A case series of 12 patients.
        J Clin Gastroenterol. 2010; 22: 562-566
        • Rohlke F.
        • Surawicz C.M.
        • Stollman N.
        Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology.
        J Clin Gastroenterol. 2010; 44: 567-570
        • MacConnachie A.A.
        • Fox R.
        • Kennedy D.R.
        • et al.
        Faecal transplant for recurrent Clostridium difficile-associated diarrhea: a UK case series.
        Q J Med. 2009; 102: 781-784
        • Rubin T.A.
        • Fessert C.E.
        • Aas J.
        Stool transplantation for older patients with Clostridium difficile infection.
        Am J Geriatr Soc. 2009; 57: 2386-2387
        • Russell G.
        • Kaplan J.
        • Ferraro M.J.
        • et al.
        Fecal bacteriotherapy for relapsing Clostridium difficile infection in a child: a proposed treatment protocol.
        Paediatrics. 2010; 126: e239-e242
        • Schwan A.
        • Sjolin S.
        • Trottestam U.
        Relapsing Clostridium difficile enterocolitis cured by rectal infusion of homologous faeces.
        Lancet. 1983; 2: 845
        • Tvede M.
        • Rask-Madsen J.
        Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients.
        Lancet. 1989; 1: 1156-1160
        • Paterson D.L.
        • Iredell J.
        • Whitby M.
        Putting back the bugs: bacterial treatment relieves chronic diarrhoea.
        Med J Aust. 1994; 160: 232-233
        • You D.M.
        • Franzos M.A.
        Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy.
        Ann Intern Med. 2008; 148: 632-633
        • Kassam Z.
        • Hundal R.
        • Marshall J.K.
        • et al.
        Fecal transplantation via retention enemas is effective for recurrent or refractory Clostridium difficile-associated diarrhea.
        Gastroenterology. 2010; 138: S207-S208
        • Sofi A.
        • Nawras A.
        • Sodeman T.
        • et al.
        Fecal bacteriotherapy works for Clostridium difficile infection–a meta-analysis.
        Am J Gastroenterol. 2011; 410 ([abstract]): S161
        • Guo B.
        • Harstall C.
        • Louie T.
        • et al.
        Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease.
        Aliment Pharmacol Ther. 2012; 35: 865-875
        • Brandt L.J.
        • Aroniadis O.C.
        • Mellow M.
        • et al.
        Long-term follow-up of colonoscopic fecal microbiota transplantation for recurrent Clostridium difficile infection.
        Am J Gastroenterol. 2012; 107: 1079-1087
        • Brandt L.J.
        • Borody T.J.
        • Campbell J.
        Endoscopic fecal microbiota transplantation: “first-line” treatment for severe Clostridium difficile infection?.
        J Clin Gastroenterol. 2011; 45: 655-657
        • Brandt L.J.
        • Aroniadis O.C.
        Long-term follow-up study of fecal microbiota transplantation (FMT) for ulcerative colitis (UC).
        Am J Gastroenterol. 2012; 1626 ([abstract]): S657
      4. Reddy S, Brandt LJ. Clostridium difficile infection and inflammatory bowel disease. J Clin Gastroenterol. E-pub 2013 Mar 15.

        • Anderson J.L.
        • Edney R.J.
        • Whelan K.
        Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease.
        Aliment Pharmacol Ther. 2012; 36: 503-516
        • Damman C.J.
        • Miller S.I.
        • Surawicz C.M.
        • et al.
        The microbiome and inflammatory bowel disease: is there a role for fecal microbiota transplantation?.
        Am J Gastroenterol. 2012; 107: 1452-1459
        • Dunlop S.P.
        • Jenkins D.
        • Neal K.R.
        • et al.
        Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in post-infectious IBS.
        Gastroenterology. 2003; 125: 1651-1659
        • Collins S.M.
        • Chang C.
        • Mearin F.
        Postinfectious chronic gut dysfunction: from bench to bedside.
        Am J Gastroenterol Suppl. 2012; 1: 2-8
        • Ringel Y.
        • Quigley E.M.M.
        • Lin H.
        Using probiotics in gastrointestinal disorders.
        Am J Gastroenterol Suppl. 2012; 1: 34-40
        • Foxx-Orenstein A.E.
        • Chey W.
        Manipulation of the gut microbiota as a novel treatment strategy for gastrointestinal disorders.
        Am J Gastroenterol Suppl. 2012; 1: 41-46
        • Collins S.M.
        • Bercik P.
        The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease.
        Gastroenterology. 2009; 136: 2003-2014
        • Sartour R.B.
        Microbial influences in inflammatory bowel diseases.
        Gastroenterology. 2008; 134: 577-594
        • Rajiilic-Stojanovic M.
        • Biagi E.
        • Heilig H.G.
        • et al.
        Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome.
        Gastroenterology. 2011; 141: 1792-1801
        • Quigley E.
        The enteric microbiota in the pathogenesis and management of constipation.
        Best Pract Res Clin Gastroenterol. 2011; 25: 119-126
        • Harrell L.
        • Wang Y.
        • Antonopoulos D.
        • et al.
        Standard colonic lavage alters the natural state of mucosal-associated microbiota in the human colon.
        PLoS One. 2012; 7: e32545
        • Andrews P.
        • Borody T.J.
        • Shortis N.P.
        • et al.
        Bacteriotherapy for chronic constipation–long term follow-up.
        Gastroenterology. 1995; 108: A563
        • Borody T.J.
        • Leis S.
        • Campbell J.
        • et al.
        Fecal microbiota transplantation (FMT) in multiple sclerosis (MS).
        Am J Gastroenterol. 2011; 106 ([abstract]): S352
        • Borody T.J.
        • Rosen D.M.
        • Torres M.
        • et al.
        Myoclonus-dystonia (M-D) mediated by GI microbiota diarrhoea treatment improves M-D symptoms.
        Am J Gastroenterol. 2011; 106: S352
        • Turnbaugh P.J.
        • Ley R.E.
        • Mahowald M.A.
        • et al.
        An obesity-associated gut microbiome with increased capacity for energy harvest.
        Nature. 2006; 444: 1027-1031
        • Finegold S.M.
        • Molitors D.
        • Song Y.
        Gastrointestinal micro flora studies in late-onset autism.
        Clin Infect Dis. 2002; 35: S6-S16
        • Borody T.J.
        • Campbell J.
        • Torres M.
        • et al.
        Reversal of idiopathic thrombocytopenic purpura (ITP) with fecal microbiota transplantation (FMT).
        Am J Gastroenterol. 2011; 106 ([abstract]): S352
        • Borody T.J.
        • Nowak A.
        • Torres M.
        • et al.
        Bacteriotherapy in chronic fatigue syndrome: a retrospective review.
        Am J Gastroenterol. 2012; 107 (A1481): S591-S592
        • Bravo J.A.
        • Forsythe P.
        • Chew M.V.
        • et al.
        Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.
        Proc Natl Acad Sci U S A. 2011; 108: 16050-16055
        • Bercik P.
        • Park A.J.
        • Sinclair D.
        • et al.
        The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.
        Neurogastroenterol Motil. 2011; 23: 1132-1139
        • Bakken J.S.
        • Borody T.
        • Brandt L.J.
        • et al.
        Fecal Microbiota Transplantation (FMT) Workgroup. Treating Clostridium difficile infection with fecal microbiota transplantation.
        Clin Gastroenterol Hepatol. 2011; 9: 1044-1049
        • Mattila E.
        • Uusitalo-Seppälä R.
        • Wuorela M.
        • et al.
        Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection.
        Gastroenterology. 2010; 142: 490-496
        • Hamilton M.J.
        • Weingarden A.R.
        • Sadowsky M.J.
        • et al.
        Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection.
        Am J Gastroenterol. 2012; 107: 761-767
        • Wilson D.E.
        • Chosewood L.C.
        Biosafety in Microbiological and Biomedical Laboratories, (BMBL), Centers for Disease Control and Prevention/National Institutes of Health.
        5th edition. U.S. Department of Public Health and Human Services, Washington, DC2009
        • Postigo R.
        • Kim J.H.
        Colonoscopic versus nasogastric fecal transplantation for the treatment of Clostridium difficile infection: a review and pooled analysis.
        Infection. 2012; 40: 643-648
        • Zipursky J.S.
        • Sidorsky T.I.
        • Freedman C.A.
        • et al.
        Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection.
        Clin Infect Dis. 2012; 55: 1652-1658
        • Bowden Jr., T.A.
        • Mansberger Jr., A.R.
        • Lykins L.E.
        Pseudomembranous enterocolitis: mechanism for restoring floral homeostasis.
        Am Surg. 1981; 47: 178-183
        • Louie T.J.
        • Louie M.R.
        • Krulicki W.
        • et al.
        Home-based fecal flora infusion to arrest multiply-recurrent Clostridium difficile infection (CDI).
        in: Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy (Washington, DC). Infectious Disease Society of America, Arlington (Va)2008
        • Rohlke F.
        • Surawicz C.M.
        • Stollman N.
        Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology.
        J Clin Gastroenterol. 2010; 44: 567-570
        • Kelly C.R.
        • deLeon L.
        • Jasutkar N.
        Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results.
        J Clin Gastroenterol. 2012; 46: 145-149
        • Lawley T.D.
        • Clare S.
        • Walker A.W.
        • et al.
        Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.
        PLoS Pathog. 2012; 8: e1002995
        • Petrof E.O.
        • Gloor G.B.
        • Vanner S.J.
        • et al.
        Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘rePOOPulating’ the gut.
        Microbiome. 2013; 1: 1-12