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  • Review Article
  • Published:

Understanding the mechanisms of faecal microbiota transplantation

Nature Reviews Gastroenterology & Hepatology volume 13, pages 508–516 (2016)Cite this article

Subjects

Key Points

  • Faecal microbiota transplantation (FMT) involves administration of the whole microbial community from healthy donor stool into the recipient's intestinal tract to normalize or modify intestinal microbiota composition and function

  • Overall suppression of microbiota and disruption of its community structure in the colon, most commonly resulting from antibiotic therapies, is the fundamental problem underlying the pathogenesis of Clostridium difficile infection (CDI)

  • FMT results in normalization of microbial diversity and community structure in patients being treated for CDI, with high rates of clinical cure

  • The restored colon microbial community could inhibit C. difficile by multiple mechanisms: competition for nutrients; direct suppression by antimicrobial peptides; bile-acid-mediated inhibition of spore germination and vegetative growth; and activation of immune-mediated colonization resistance

Abstract

This Review summarizes mechanistic investigations in faecal microbiota transplantation (FMT), which has increasingly been adapted into clinical practice as treatment for Clostridium difficile infection (CDI) that cannot be eliminated with antibiotics alone. Administration of healthy donor faecal microbiota in this clinical situation results in its engraftment and restoration of normal gut microbial community structure and functionality. In this Review, we consider several main mechanisms for FMT effectiveness in treatment of CDI, including direct competition of C. difficile with commensal microbiota delivered by FMT, restoration of secondary bile acid metabolism in the colon and repair of the gut barrier by stimulation of the mucosal immune system. Some of these mechanistic insights suggest possibilities for developing novel, next-generation CDI therapeutics. FMT might also have potential applications for non-CDI indications. The gut can become a reservoir of other potential antibiotic-resistant pathogens under pressure of antibiotic treatments, and restoration of normal microbial community structure by FMT might be a promising approach to protect against infections with these pathogens as well. Finally, FMT could be considered for multiple chronic diseases that are associated with some form of dysbiosis. However, considerable research is needed to optimize the FMT protocols for such applications before their therapeutic promise can be evaluated.

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Figure 1: Loss of indigenous intestinal microbiota leads to vulnerability to C. difficile infection.

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Acknowledgements

The authors were supported in part by the NIH Grant 1R21-AI114722-01 and Minnesota's Discovery, Research and Innovation Economy grant.

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Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology, Center for Immunology and BioTechnology Institute, Medical Biosciences Building, 2101 6th Street South East

    Alexander Khoruts

  2. University of Minnesota, Minneapolis, 55414, Minnesota, USA

    Alexander Khoruts

  3. Department of Soil, Water, and Climate, BioTechnology Institute, and Microbial and Plant Genomics Institute, University of Minnesota, 140 Gortner Lab, 1479 Gortner Avenue, St. Paul, 55108, Minnesota, USA

    Michael J. Sadowsky

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Both authors made substantial discussions to content and reviewed/edited the manuscript before submission. A.K. researched data and wrote the article.

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Correspondence to Alexander Khoruts.

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Competing interests

A.K. and M.J.S. have received research grant support from Crestovo, a company working to commercialize faecal microbiota transplantation. A.K. and M.J.S. have also filed a patent application that relates to the composition and methods for transplantation of colon microbiota.

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Khoruts, A., Sadowsky, M. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol 13, 508–516 (2016). https://doi.org/10.1038/nrgastro.2016.98

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