Microbiome therapeutics for the treatment of recurrent Clostridioides difficile infection

ABSTRACT

Introduction

The gut microbiome is implicated in Clostridioides difficile infection (CDI) and recurrent CDI (rCDI).

Areas covered

This review covers the mechanisms by which microbiome therapeutics treat rCDI, their efficacy and safety, and clinical trial design considerations for future research.

Expert opinion

Altering the chemical environment of the gut and reconstituting colonization resistance is a promising strategy for preventing and treating rCDI. Fecal microbiota transplant (FMT) is safe and effective for the treatment of rCDI. However, limitations of FMT have prompted investigation into alternative microbiome therapeutics. These alternative microbiome therapies require further evaluation, and adaptive trial designs should be strongly considered to more rapidly discern variables including the need for bowel preparation, timing and selection of pre-treatment antibiotics, and dose and duration of microbiome therapeutics. A broad range of adverse events must be prospectively evaluated in these controlled trials, as microbiome therapeutics have the potential for numerous effects. Future studies will lead to a greater understanding of the mechanisms by which microbiome therapies can break the cycle of rCDI, which should ultimately yield a personalized approach to rCDI treatment that restores an individual’s specific deficit(s) in colonization resistance to C. difficile.

KEYWORDS:

• C. difficile
• microbiome
• microbiome therapeutics
• fecal microbiota transplant

Article highlights

• Modifying the metabolic environment of the gut microbiome and reconstituting C. difficile colonization resistance is a promising strategy for microbiome therapeutics to prevent and treat recurrent C. difficile infection.

• Fecal microbiota transplant is safe and effective for the treatment of recurrent C. difficile infection.

• Alternatives to fecal microbiota transplant have been developed, with a range of microbial compositions and preparation methods, and show promise in clinical trials.

• Microbiome therapeutics for recurrent C. difficile infection should be thoroughly evaluated for a range of adverse events (not only gastrointestinal or infectious).

• Future research will lead to a greater understanding of the therapeutic mechanisms by which microbiome therapeutics break the cycle of recurrent C. difficile infection with the goal of optimizing and personalizing treatment approaches.

Declaration of interest

P Bloom holds a research grant from Vedanta Biosciences. VB Young serves as a consultant to Vedanta Biosciences and Debiopharm. He is Senior Editor for mSphere (American Society for Microbiology) and acts on the External Advisory Board for University of Oklahoma COBRE. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

P Bloom has received an American College of Gastroenterology Junior Faculty Award and VB Young an NIH Award (AI124255) in support of their work on the microbiome.