Fecal microbiota transplantation (FMT) has been utilized sporadically for over 50 years. In the past few years, Clostridium difficile infection (CDI) epidemics in the USA and Europe have resulted in the increased use of FMT, given its high efficacy in eradicating CDI and associated symptoms. As more patients request treatment and more clinics incorporate FMT into their treatment repertoire, reports of applications outside of CDI are emerging, paving the way for the use of FMT in several idiopathic conditions. Interest in this therapy has largely been driven by new research into the gut microbiota, which is now beginning to be appreciated as a microbial human organ with important roles in immunity and energy metabolism. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of FMT for several disorders, including IBD, IBS, the metabolic syndrome, neurodevelopmental disorders, autoimmune diseases and allergic diseases, among others. The field of microbiota-related disorders is currently in its infancy; it certainly is an exciting time in the burgeoning science of FMT and we expect to see new and previously unexpected applications in the near future. Well-designed and well-executed randomized trials are now needed to further define these microbiota-related conditions.
Fecal microbiota transplantation (FMT) is arguably the most effective method in treating recalcitrant Clostridium difficile infection (CDI)
FMT is the engraftment of microbiota from a healthy donor into a recipient, which results in restoration of the normal gut microbial community structure
Standardization of FMT protocols should overcome the major practical barriers to its wider clinical implementation
As multiple major diseases might be linked to dysfunction of gut microbiota, FMT could have potential applications beyond CDI
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Backhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A. & Gordon, J. I. Host–bacterial mutualism in the human intestine. Science 307, 1915–1920 (2005).
Dethlefsen, L., McFall-Ngai, M. & Relman, D. A. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449, 811–818 (2007).
Yazdanbakhsh, M., Kremsner, P. G. & van Ree, R. Allergy, parasites, and the hygiene hypothesis. Science 296, 490–494 (2002).
Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323 (2009).
Blaser, M. J. Who are we? Indigenous microbes and the ecology of human diseases. EMBO Rep. 7, 956–960 (2006).
Mullard, A. Microbiology: the inside story. Nature 453, 578–580 (2008).
Metchnikoff, E. & Mitchell, P. C. S. The Prolongation of Life: optimistic studies (William Heinemann, London, 1907).
Salminen, S. et al. Functional food science and gastrointestinal physiology and function. Br. J. Nutr. 80 (Suppl. 1), S147–S171 (1998).
McDonald, L. C., Owings, M. & Jernigan, D. B. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996–2003. Emerg. Infect. Dis. 12, 409–415 (2006).
Jarvis, W. R., Schlosser, J., Jarvis, A. A. & Chinn, R. Y. National point prevalence of Clostridium difficile in US health care facility inpatients. Am. J. Infect. Control 37, 263–270 (2009).
Ricciardi, R., Rothenberger, D. A., Madoff, R. D. & Baxter, N. N. Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States. Arch. Surg. 142, 624–631 (2007).
Rupnik, M., Wilcox, M. H. & Gerding, D. N. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol. 7, 526–536 (2009).
Kuijper, E. J. et al. Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Euro Surveill. 13, 18942 (2008).
Kelly, C. P. & LaMont, J. T. Clostridium difficile—more difficult than ever. N. Engl. J. Med. 359, 1932–1940 (2008).
Louie, T. J. et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N. Engl. J. Med. 364, 422–431 (2011).
Hu, M. Y. et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 136, 1206–1214 (2009).
Chang, J. Y. et al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J. Infect. Dis. 197, 435–438 (2008).
Tvede, M. & Rask-Madsen, J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1, 1156–1160 (1989).
Eiseman, B., Silen, W., Bascom, G. S. & Kauvar, A. J. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 44, 854–859 (1958).
Bakken, J. S. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anaerobe 15, 285–289 (2009).
Flotterod, O. & Hopen, G. Refractory Clostridium difficile infection. Untraditional treatment of antibiotic-induced colitis [Norwegian]. Tidsskr. Nor. Laegeforen 111, 1364–1365 (1991).
Lund-Tonnesen, S., Berstad, A., Schreiner, A. & Midtvedt, T. Clostridium difficile-associated diarrhea treated with homologous feces [Norwegian]. Tidsskr. Nor. Laegeforen 118, 1027–1030 (1998).
Persky, S. E. & Brandt, L. J. Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am. J. Gastroenterol. 95, 3283–3285 (2000).
Van Nood, E., Speelman, P., Kuijper, E. J. & Keller, J. J. Struggling with recurrent Clostridium difficile infections: is donor faeces the solution? Euro Surveill. 14, 19316 (2009).
Borody, T. J., Leis, S., Pang, G. & Wettstein, A. R. Fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection. UpToDate [online], (2010).
Bakken, J. S. et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/j.cgh.2011.08.014.
Brandt, L. J., Borody, T. J. & Campbell, J. Endoscopic fecal microbiota transplantation: “first-line” treatment for severe Clostridium difficile infection? J. Clin. Gastroenterol. 45, 655–657 (2011).
Rohlke, F., Surawicz, C. M. & Stollman, N. Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. J. Clin. Gastroenterol. 44, 567–570 (2010).
You, D. M., Franzos, M. A. & Holman, R. P. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann. Intern. Med. 148, 632–633 (2008).
Sailhamer, E. A. et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch. Surg. 144, 433–439 (2009).
Grehan, M. J. et al. Durable alteration of the colonic microbiota by the administration of donor fecal flora. J. Clin. Gastroenterol. 44, 551–561 (2010).
Tannock, G. W. et al. Analysis of the fecal microflora of human subjects consuming a probiotic product containing Lactobacillus rhamnosus DR20. Appl. Environ. Microbiol. 66, 2578–2588 (2000).
Khoruts, A., Dicksved, J., Jansson, J. K. & Sadowsky, M. J. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J. Clin. Gastroenterol. 44, 354–360 (2010).
Floch, M. H. Fecal bacteriotherapy, fecal transplant, and the microbiome. J. Clin. Gastroenterol. 44, 529–530 (2010).
Gustaffson, A., Berstad, A., Lund-Tønnesen, S., Midtvedt, T. & Norin, E. The effect of fecal enema on five microflora-associated characteristics in patients with antibiotic-associated diarrhea. Scand. J. Gastroenterol. 34, 580–586 (1999).
Kahn, S., Gorawara-Bhat, R. & Rubin, D. T. Fecal bacteriotherapy for ulcerative colitis: patients are ready, are we? Inflamm. Bowel Dis. http://dx.doi.org/10.1002/ibd.21775.
Podolsky, D. K. Inflammatory bowel disease. N. Engl. J. Med. 347, 417–429 (2002).
Maloy, K. J. & Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306 (2011).
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).
Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).
Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).
Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).
Bennet, J. D. & Brinkman, M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet 1, 164 (1989).
Borody, T. J., Warren, E. F., Leis, S., Surace, R. & Ashman, O. Treatment of ulcerative colitis using fecal bacteriotherapy. J. Clin. Gastroenterol. 37, 42–47 (2003).
Andrews, P., Borody, T. J., Shortis, N. P. & Thompson, S. Bacteriotherapy for chronic constipation—long term follow-up. Gastroenterology 108 (Suppl. 2), A563 (1995).
Borody, T. J. et al. Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Med. J. Aust. 150, 604 (1989).
Borody, T. J., Leis, S., Campbell, J., Torres, M. & Nowak, A. Fecal microbiota transplantation (FMT) in multiple sclerosis (MS) [abstract]. Am. J. Gastroenterol. 106, S352 (2011).
Borody, T. J., Campbell, J., Torres, M., Nowak, A. & Leis, S. Reversal of idiopathic thrombocytopenic purpura (ITP) with fecal microbiota transplantation (FMT) [abstract]. Am. J. Gastroenterol. 106, S352 (2011).
Borody, T. J. Bacteriotherapy for chronic fatigue syndrome: a long-term follow up study. Presented at the 1995 CFS National Consensus Conference.
Moore, P. R. & Evenson, A. Use of sulfasuxidine, streptothricin, and streptomycin in nutritional studies with the chick. J. Biol. Chem. 165, 437–441 (1946).
Jukes, T. H. & Williams, W. L. Nutritional effects of antibiotics. Pharmacol. Rev. 5, 381–420 (1953).
Haight, T. H. & Pierce, W. E. Effect of prolonged antibiotic administration of the weight of healthy young males. J. Nutr. 56, 151–161 (1955).
Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).
Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).
Schwiertz, A. et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18, 190–195 (2010).
Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004).
Backhed, F., Manchester, J. K., Semenkovich, C. F. & Gordon, J. I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl Acad. Sci. USA 104, 979–984 (2007).
Kahn, B. B., Alquier, T., Carling, D. & Hardie, D. G. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell. Metab. 1, 15–25 (2005).
Kimura, I. et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc. Natl Acad. Sci. USA 108, 8030–8035 (2011).
Vrieze, A. et al. Metabolic effects of transplanting gut microbiota from lean donors to subjects with metabolic syndrome [abstract A90]. Presented at the European Association for the Study of Diabetes meeting (2010).
Cutolo, L. C., Kleppel, N. H., Freund, H. R. & Holker, J. Fecal feedings as therapy in Staphylococcus enterocolitis. N. Y. State J. Med. 59, 3831–3833 (1959).
Fenton, S., Stephenson, D., Weder, C. & Saskatoon S. Pseudomembranous colitis associated with antibiotic therapy—an emerging entity. CMA Journal 111, 1110–1114 (1974).
Bowden, T. A. Jr, Mansberger, A. R. Jr & Lykins, L. E. Pseudomembraneous enterocolitis: mechanism for restoring floral homeostasis. Am. Surg. 47, 178–183 (1981).
Schwan, A., Sjölin, S., Trottestam, U. & Aronsson, B. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of normal faeces. Scand. J. Infect. Dis. 16, 211–215 (1984).
Paterson, D. L., Iredell, J. & Whitby, M. Putting back the bugs: bacterial treatment relieves chronic diarrhoea. Med. J. Aust. 160, 232–233 (1994).
Faust, G., Langelier, D., Haddad, H. & Menard, D. B. Treatment of recurrent pseudomembranous colitis (RPMC) with stool transplantation (ST): report of six (6) cases [abstract 002]. Presented at the 2002 Canadian Digestive Diseases Week.
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. 36, 580–585 (2003).
Jorup-Rönström, C., Hakanson, A. & Persoon, A. K. Feces culture successful therapy in Clostridium difficile diarrhea [abstract]. Larkartidningen 103, 3603–3605 (2006).
Wettstein, A. et al. Fecal bacteriotherapy—an effective treatment for relapsing symptomatic Clostridium difficile infection [abstract G67]. Presented at the 15th United European Gastroenterology Week.
Louie, T. J. Home-based fecal flora infusion to arrest multiple-recurrent Clostrdium difficile infection (CDI). Presented at the 48th Interscience Conference on Antimicrobial Agents & Chemotherapy in conjunction with the Infectious Disease Society of America.
Nieuwdorp, M. et al. Treatment of recurrent Clostridium difficile-associated diarrhea with a suspension of donor feces [Dutch]. Ned. Tijdschr. Geneeskd. 152, 1927–1932 (2008).
Hellemans, R., Naegels, S. & Holvoet, J. Fecal transplantation for recurrent Clostridium difficile colitis, an underused treatment modality. Acta Gastroenterol. Belg. 72, 269–270 (2009).
MacConnachie, A. A., Fox, R., Kennedy, D. R. & Seaton, R. A. Fecal transplant for recurrent Clostridium difficile-associated diarrhea: a UK case series. QJM 102, 781–784 (2009).
Arkkila, P. E. et al. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Gastroenterology 138 (Suppl. 1), S5 (2010).
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. 44, 562–566 (2010).
Silverman, M. S., Davis, I. & Pillai, D. R. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin. Gastroenterol. Hepatol. 5, 471–473 (2010).
Garborg, K., Waagsbø, B., Stallemo, A., Matre, J. & Sundøy, A. Results of faecal donor instillation therapy for recurrent Clostridium difficile-associated diarrhoea. Scand. J. Infect. Dis. 42, 857–861 (2010).
Russell, G., Kaplan, J., Ferraro, M. J. & Michelow, I. C. Fecal bacteriotherapy for relapsing Clostridium difficile infection in a child: a proposed treatment protocol. Pediatrics 126, e239–e242 (2010).
Kelly, C. & de Leon, L. Successful treatment of recurrent Clostridium difficile infection with donor stool administered at colonoscopy: a case series [abstract 366]. Am. J. Gastroenterol. 105, S135 (2010).
Mellow, M. & Kanatzar, A. Colonoscopic fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection [abstract]. Am. J. Gastroenterol. 105, S135 (2010).
Kassam, Z., Hundal, R., Marshall, J. K. & Lee, C. H. Fecal transplantation via retention enemas is effective for recurrent or refractory Clostridium difficile-associated diarrhea. Gastroenterology 138, S207–S208 (2010)
Kelly, C., Jasutkar, N. & de Leon, L. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. J. Clin. Gastroenterol. (in press).
This work was in part supported by NIH grant R21AI091907 (A. Khoruts). The authors would like to acknowledge J. Campbell, Centre for Digestive Diseases, Sydney, Australia, for her skilled assistance in various technical aspects of manuscript preparation and editorial support.
Thomas J. Borody has a pecuniary interest in the Centre for Digestive Diseases, where fecal microbiota transplantion is a treatment option, and has filed patents in this approach. Alexander Khoruts has filed patents in the field of fecal microbiota transplantation for the University of Minnesota, USA.
About this article
Cite this article
Borody, T., Khoruts, A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol 9, 88–96 (2012). https://doi.org/10.1038/nrgastro.2011.244
This article is cited by
Scientific Reports (2023)
Current Oncology Reports (2023)
Journal of Cancer Research and Clinical Oncology (2023)
Gut microbiota-derived ursodeoxycholic acid from neonatal dairy calves improves intestinal homeostasis and colitis to attenuate extended-spectrum β-lactamase-producing enteroaggregative Escherichia coli infection
Berberine and its derivatives represent as the promising therapeutic agents for inflammatory disorders
Pharmacological Reports (2022)