Microbial metabolic profiling reshapes NF-κB-mediated immune metabolic network: a new mechanism for CRC development.

backgroundThe progression of colorectal cancer (CRC) is driven by multiple factors, including genetic mutations, metabolic reprogramming, immune escape, and dysbiosis of the intestinal microbiota. NF-κB acts as a central signaling hub within the tumor microenvironment that integrates inflammatory, metabolic, and immune cues to promote CRC progression.

methodsThis review systematically summarizes the roles of key immune pathways and metabolic reprogramming in CRC pathogenesis and outlines CRC-associated alterations in gut microbial profiles. The synthesis of functional microbial metabolites, including short-chain fatty acids (SCFAs), secondary bile acids, and hydrogen sulfide (H₂S), modulates NF-κB activity through receptor-mediated signaling, regulation of signal transduction complexes, and epigenetic mechanisms, thereby reshaping tumor metabolism and immune responses. Notably, several metabolites demonstrate concentration-dependent biphasic effects on NF-κB signaling, highlighting the dynamic and context-dependent nature of microbial–host interactions during tumor progression.

conclusionsTargeting the metabolic activities of gut microbiota to regulate NF-κB signaling represents a promising multi-target strategy for CRC prevention and therapy. Future research should prioritize the construction of integrated “microbiota–metabolite–target” regulatory networks and the development of individualized microecological intervention strategies.