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Fecal microbiota transplantation and emerging applications

Abstract

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.

Key Points

  • 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

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Figure 1: FMT for patients with recalcitrant CDI.

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References

  1. 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).

    Article  PubMed  Google Scholar 

  2. Dethlefsen, L., McFall-Ngai, M. & Relman, D. A. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449, 811–818 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Yazdanbakhsh, M., Kremsner, P. G. & van Ree, R. Allergy, parasites, and the hygiene hypothesis. Science 296, 490–494 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Blaser, M. J. Who are we? Indigenous microbes and the ecology of human diseases. EMBO Rep. 7, 956–960 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mullard, A. Microbiology: the inside story. Nature 453, 578–580 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Metchnikoff, E. & Mitchell, P. C. S. The Prolongation of Life: optimistic studies (William Heinemann, London, 1907).

    Google Scholar 

  8. Salminen, S. et al. Functional food science and gastrointestinal physiology and function. Br. J. Nutr. 80 (Suppl. 1), S147–S171 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 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).

    Article  PubMed  Google Scholar 

  11. 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).

    Article  PubMed  Google Scholar 

  12. Rupnik, M., Wilcox, M. H. & Gerding, D. N. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol. 7, 526–536 (2009).

    CAS  PubMed  Google Scholar 

  13. Kuijper, E. J. et al. Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Euro Surveill. 13, 18942 (2008).

    PubMed  Google Scholar 

  14. Kelly, C. P. & LaMont, J. T. Clostridium difficile—more difficult than ever. N. Engl. J. Med. 359, 1932–1940 (2008).

    Article  CAS  PubMed  Google Scholar 

  15. Louie, T. J. et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N. Engl. J. Med. 364, 422–431 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Hu, M. Y. et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 136, 1206–1214 (2009).

    Article  PubMed  Google Scholar 

  17. Chang, J. Y. et al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J. Infect. Dis. 197, 435–438 (2008).

    Article  PubMed  Google Scholar 

  18. Tvede, M. & Rask-Madsen, J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1, 1156–1160 (1989).

    Article  CAS  PubMed  Google Scholar 

  19. 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).

    CAS  PubMed  Google Scholar 

  20. Bakken, J. S. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anaerobe 15, 285–289 (2009).

    Article  PubMed  Google Scholar 

  21. Flotterod, O. & Hopen, G. Refractory Clostridium difficile infection. Untraditional treatment of antibiotic-induced colitis [Norwegian]. Tidsskr. Nor. Laegeforen 111, 1364–1365 (1991).

    CAS  PubMed  Google Scholar 

  22. 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).

    CAS  PubMed  Google Scholar 

  23. 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).

    CAS  PubMed  Google Scholar 

  24. 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).

    Article  PubMed  Google Scholar 

  25. Borody, T. J., Leis, S., Pang, G. & Wettstein, A. R. Fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection. UpToDate [online], (2010).

  26. 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.

  27. 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).

    Article  PubMed  Google Scholar 

  28. 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).

    Article  PubMed  Google Scholar 

  29. 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).

    Article  PubMed  Google Scholar 

  30. Sailhamer, E. A. et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch. Surg. 144, 433–439 (2009).

    Article  PubMed  Google Scholar 

  31. 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).

    Article  PubMed  Google Scholar 

  32. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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).

    PubMed  Google Scholar 

  34. Floch, M. H. Fecal bacteriotherapy, fecal transplant, and the microbiome. J. Clin. Gastroenterol. 44, 529–530 (2010).

    Article  PubMed  Google Scholar 

  35. 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).

    Article  Google Scholar 

  36. 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.

  37. Podolsky, D. K. Inflammatory bowel disease. N. Engl. J. Med. 347, 417–429 (2002).

    Article  CAS  PubMed  Google Scholar 

  38. Maloy, K. J. & Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bennet, J. D. & Brinkman, M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet 1, 164 (1989).

    Article  CAS  PubMed  Google Scholar 

  45. 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).

    Article  PubMed  Google Scholar 

  46. Andrews, P., Borody, T. J., Shortis, N. P. & Thompson, S. Bacteriotherapy for chronic constipation—long term follow-up. Gastroenterology 108 (Suppl. 2), A563 (1995).

    Google Scholar 

  47. 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).

    CAS  PubMed  Google Scholar 

  48. 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).

    Google Scholar 

  49. 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).

    Google Scholar 

  50. Borody, T. J. Bacteriotherapy for chronic fatigue syndrome: a long-term follow up study. Presented at the 1995 CFS National Consensus Conference.

  51. Moore, P. R. & Evenson, A. Use of sulfasuxidine, streptothricin, and streptomycin in nutritional studies with the chick. J. Biol. Chem. 165, 437–441 (1946).

    CAS  PubMed  Google Scholar 

  52. Jukes, T. H. & Williams, W. L. Nutritional effects of antibiotics. Pharmacol. Rev. 5, 381–420 (1953).

    CAS  PubMed  Google Scholar 

  53. Haight, T. H. & Pierce, W. E. Effect of prolonged antibiotic administration of the weight of healthy young males. J. Nutr. 56, 151–161 (1955).

    Article  CAS  PubMed  Google Scholar 

  54. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

    Article  CAS  PubMed  Google Scholar 

  55. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

    Article  PubMed  Google Scholar 

  56. Schwiertz, A. et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18, 190–195 (2010).

    Article  Google Scholar 

  57. Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  58. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 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).

    Article  CAS  PubMed  Google Scholar 

  60. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 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).

  62. 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).

    CAS  PubMed  Google Scholar 

  63. Fenton, S., Stephenson, D., Weder, C. & Saskatoon S. Pseudomembranous colitis associated with antibiotic therapy—an emerging entity. CMA Journal 111, 1110–1114 (1974).

    CAS  Google Scholar 

  64. Bowden, T. A. Jr, Mansberger, A. R. Jr & Lykins, L. E. Pseudomembraneous enterocolitis: mechanism for restoring floral homeostasis. Am. Surg. 47, 178–183 (1981).

    PubMed  Google Scholar 

  65. 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).

    Article  CAS  PubMed  Google Scholar 

  66. Paterson, D. L., Iredell, J. & Whitby, M. Putting back the bugs: bacterial treatment relieves chronic diarrhoea. Med. J. Aust. 160, 232–233 (1994).

    CAS  PubMed  Google Scholar 

  67. 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.

  68. 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).

    Article  PubMed  Google Scholar 

  69. Jorup-Rönström, C., Hakanson, A. & Persoon, A. K. Feces culture successful therapy in Clostridium difficile diarrhea [abstract]. Larkartidningen 103, 3603–3605 (2006).

    Google Scholar 

  70. 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.

  71. 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.

  72. 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).

    CAS  PubMed  Google Scholar 

  73. Hellemans, R., Naegels, S. & Holvoet, J. Fecal transplantation for recurrent Clostridium difficile colitis, an underused treatment modality. Acta Gastroenterol. Belg. 72, 269–270 (2009).

    CAS  PubMed  Google Scholar 

  74. 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).

    Article  CAS  PubMed  Google Scholar 

  75. Arkkila, P. E. et al. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Gastroenterology 138 (Suppl. 1), S5 (2010).

    Google Scholar 

  76. 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).

    Article  PubMed  Google Scholar 

  77. 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).

    Article  Google Scholar 

  78. 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).

    Article  PubMed  Google Scholar 

  79. 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).

    Article  PubMed  Google Scholar 

  80. 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).

    Google Scholar 

  81. Mellow, M. & Kanatzar, A. Colonoscopic fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection [abstract]. Am. J. Gastroenterol. 105, S135 (2010).

    Article  Google Scholar 

  82. 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)

    Article  Google Scholar 

  83. 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).

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Acknowledgements

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.

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Both authors contributed equally to researching data for the article, discussion of content, writing, reviewing and editing the manuscript.

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Correspondence to Thomas J. Borody.

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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.

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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

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