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

The 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. This 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. Targeting 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. Gut microbial metabolites (GMMs) reshape NF-κB-mediated metabolic-immune networks in CRC. NF-κB is the regulatory hub of CRC, integrating inflammatory signals, metabolic reprogramming, and immune evasion mechanisms. Phylum-specific microbial metabolic profiles offer multi-target strategies for precision microbiota-based CRC therapy.