Microbiota-associated post-translational remodeling of immune cell states in gastrointestinal cancer

Microbial communities influence gastrointestinal (GI) cancer through metabolic exchange and immune regulation. Post-translational modifications (PTMs) can connect these signals to changes in chromatin, protein function and immune-cell states. This narrative review examines histone and non-histone modifications to explore how microbial inputs and host metabolism intersect in the regulation of immune-cell states and tumor immunity. Microbial metabolites can influence acyl-donor availability and PTM enzyme activity, while microbial sensing can reprogram host metabolism and downstream modification states. These routes provide a framework for understanding changes in lymphoid and myeloid cell function, whose consequences for tumor immunity depend on cellular and disease context. Among the studies assessed, evidence linking microbial interventions to immune-cell PTM changes in GI cancer is concentrated in colorectal cancer and its metastatic models. Findings from nonmalignant models, other cancers and host metabolic studies provide complementary insights into potentially relevant mechanisms. Their extension to microbiota–immune interactions in GI tumors requires attention to both microbial involvement and the functional contribution of specific modifications. Understanding how microbial inputs converge with host metabolism at the level of PTM regulation may reveal opportunities to modulate tumor immunity. Defining metabolite sources and cellular exposure, resolving the functions of individual modifications, and validating pathways in relevant anatomical and therapeutic settings will be important for identifying mechanisms that can inform biomarker and therapeutic development.