Evaluating the Necessity of Live Microbes in Fecal Microbiota Transplantation for C. difficile Recurrence: Insights from a Non-Inferiority Trial

Introduction

Recurrent Clostridioides difficile infection (CDI) remains a significant healthcare challenge, with traditional treatments often centered around antibiotic use which may paradoxically disrupt gut microbiota further. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy, boasting cure rates exceeding 85%. Its success is primarily attributed to restoring a healthy microbial ecosystem within the colon. Despite its efficacy, the underlying mechanisms—particularly whether live microbes are essential—remain under investigation.

This trial critically evaluates whether a sterile, lyophilised fecal filtrate (LSFF), containing microbial metabolites and DNA but devoid of live microbes, can match the efficacy of conventional lyophilised donor stool (LFMT). Confirming non-inferiority could have profound implications for safety, logistics, and standardisation of microbiota-based therapies.