Microbial engraftment and immune regulation during fecal microbiota transplantation and immune checkpoint inhibitor therapy.

Abstract

The gut microbiota is a critical determinant of both therapeutic efficacy and immune-related toxicity during cancer immunotherapy with immune checkpoint inhibitors (ICIs). Fecal microbiota transplantation (FMT) has emerged as a strategy to introduce beneficial microbial functions, yet clinical outcomes remain variable. In this Review, we integrate evidence from recent clinical trials combining FMT with ICIs in a mechanism-based framework for understanding this variability and to guide safer clinical applications. We discuss how specific microbial functional programs can either buffer or lower thresholds for immune dysregulation and outline implications for donor selection, longitudinal monitoring, and trial design in oncology.