Bariatric surgery-induced gut microbiota remodeling and innate immune activation: implications for gastrointestinal cancer immunotherapy

Bariatric and metabolic surgery (MBS)—primarily sleeve gastrectomy and Roux-en-Y gastric bypass—provides a unique human model for evaluating how profound immunometabolic rewiring alters cancer susceptibility and therapeutic responsiveness. Beyond weight loss, post-surgical anatomical reconfiguration permanently reshapes the gut microbial ecosystem, alters enterohepatic bile acid circulation, and attenuates systemic meta-inflammation. This review synthesizes emerging evidence linking post-bariatric gut microbiota remodeling to innate immune activation, with a specific focus on its translational potential in gastrointestinal (GI) cancer immunotherapy. Mechanistically, post-operative shifts in secondary bile acids, short-chain fatty acids, and microbial pattern-associated molecular patterns (PAMPs) act through key innate sensors—including FXR, TGR5, AhR, and the cGAS-STING pathway—to reprogram tumor-associated macrophages from an M2-like immunosuppressive state toward an anti-tumor phenotype. These cellular adjustments promote dendritic cell priming, stimulate type I interferon production, and enhance CXCL11-dependent cytotoxic lymphocyte recruitment, thereby remodeling “cold” gastrointestinal tumor microenvironments. By deconstructing the multi-layered crosstalk across the gut–liver and gut–tumor axes, we outline a translational framework for leveraging non-surgical surrogates—including defined microbial consortia, engineered postbiotics, and targeted pattern-recognition receptor agonists—to overcome primary resistance to immune checkpoint inhibitors in gastrointestinal malignancies.