The relationship between gut microbiota and cancer immune response and immunotherapy

The gut microbiota critically regulates cancer immunity and immunotherapy outcomes. It does so through complex, bidirectional interactions with the host immune system. Key microbial metabolites drive this process. These include short-chain fatty acids (SCFAs), tryptophan derivatives, inosine, trimethylamine N-oxide (TMAO), and bile acids. These molecules direct immune cell differentiation and activity via pattern recognition receptor signaling and epigenetic regulation. Clinical studies have linked specific microbial compositions to responses to immune checkpoint inhibitors (ICIs) across multiple cancer types. These studies also highlight a dual role of the microbiota. It can both increase therapeutic efficacy and mitigate immune-related adverse events (irAEs). Several therapeutic strategies are under active investigation. These include fecal microbiota transplantation (FMT), probiotics, prebiotics, and dietary interventions. However, challenges remain regarding engraftment, standardization, and formulation consistency. Large-scale, well-designed studies are still needed. Such studies will help establish the gut microbiota as a reliable prognostic biomarker and a viable therapeutic adjunct in cancer immunotherapy.