| The gut microbiota is a host factor that influences the response of colorectal cancer (CRC) to immune checkpoint inhibitors (ICIs) and may contribute to primary and acquired resistance. CRC with deficient mismatch repair/high microsatellite instability (dMMR/MSI-H) is more likely to respond to ICIs, whereas CRC with proficient mismatch repair/microsatellite stability (pMMR/MSS) is generally insensitive to ICI monotherapy; this immune context may determine the scope for microbiota-directed interventions. Microbial components and metabolites can regulate dendritic cell activation and antigen presentation, cluster of differentiation 8-positive (CD8+) T-cell infiltration and effector function, and immunosuppression mediated by myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages. Some species and metabolites have bidirectional effects that depend on the strain, target cell, host state, and treatment conditions. This review examines the regulatory relationships among microbes, metabolites, immune cells, and the tumor microenvironment and evaluates the evidence for dietary modulation, fecal microbiota transplantation, probiotics, and prebiotics. Evidence in CRC remains predominantly preclinical or derived from small early-phase trials; standardized longitudinal studies and randomized controlled trials are needed to establish reproducible functional biomarkers, the independent contribution of each intervention, and the patient populations most likely to benefit. |
