Fecal Microbiota Transplantation in Colorectal Cancer: From Immune Regulation to Immunotherapy

The gut microbiome influences colorectal cancer (CRC) progression and responses to immune checkpoint inhibitors (ICIs), with immunotherapy resistance remaining a major challenge in microsatellite-stable/mismatch repair-proficient (MSS/pMMR) CRC. This review examines the mechanisms and translational potential of fecal microbiota transplantation (FMT) in CRC immunotherapy, focusing on the interplay among microbial functions, metabolic alterations, and immune microenvironment remodeling. Current evidence suggests that FMT may influence antitumor immunity beyond restoring microbial diversity by transferring functionally relevant microbial communities, metabolic profiles, and immunomodulatory signals. These changes may affect antigen presentation, inflammatory signaling, T-cell activity, and myeloid-cell states, thereby shaping the tumor immune microenvironment and potentially modulating responses to PD-1/PD-L1 blockade. However, the clinical efficacy of FMT in CRC, the determinants of successful microbial engraftment, and the mechanisms linking donor-derived microbial functions to therapeutic outcomes remain incompletely understood. Integrating defined microbial consortia, metabolite-based interventions, and multi-omics-guided patient stratification may help advance FMT toward mechanism-driven precision microbiome therapy and inform strategies to improve CRC immunotherapy outcomes.