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Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology

Abstract

Faecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent Clostridioides difficile infection that cannot be cured with antibiotics alone. Understanding the complex biology and pathogenesis of C. difficile infection, which we discuss in this Perspective, is essential for understanding the potential mechanisms by which FMT cures this disease. Although FMT has already entered clinical practice, different microbiota-based products are currently in clinical trials and are vying for regulatory approval. However, all these therapeutics belong to an entirely new class of agents that require the development of a new branch of pharmacology. Characterization of microbiota therapeutics uses novel and rapidly evolving technologies and requires incorporation of microbial ecology concepts. Here, we consider FMT within a pharmacological framework, including its essential elements: formulation, pharmacokinetics and pharmacodynamics. From this viewpoint, multiple gaps in knowledge become apparent, identifying areas that require systematic research. This knowledge is needed to help clinical providers use microbiota therapeutics appropriately and to facilitate development of next-generation microbiota products with improved safety and efficacy. The discussion here is limited to FMT as a representative of microbiota therapeutics and recurrent C. difficile as the indication; however, consideration of the intrinsic basic principles is relevant to this entire class of microbiota-based therapeutics.

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Fig. 1: Pathophysiology of Clostridioides difficile infection.
Fig. 2: Determinants of drug pharmacology for live microbial agents.
Fig. 3: Intestinal microbiota as the pharmacological target.

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Acknowledgements

A.K. and M.J.S. acknowledge that this work was supported in part by the US Department of Defense grant W81XWH-17-1-0636.

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A.K. and M.J.S. have patents related to the preparation of faecal microbiota for transplantation. C.S. declares no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks J. Allegretti, G. Cammarota, B. Mullish and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Khoruts, A., Staley, C. & Sadowsky, M.J. Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology. Nat Rev Gastroenterol Hepatol 18, 67–80 (2021). https://doi.org/10.1038/s41575-020-0350-4

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