The gut microbiota and colorectal cancer: Molecular insights and translational implications

In recent years, the gut microbiota have identified as a modifiable key environmental factor influencing the development and progression of colorectal cancer (CRC). Molecular epidemiological studies, including cross-sectional and prospective cohort designs, have consistently identified distinct microbial dysbiosis in CRC patients, characterized by an enrichment of pro-inflammatory and genotoxin-producing bacteria, alongside a reduction in protective commensals. Mendelian randomization analyses further support a causal role for specific microbial taxa in CRC pathogenesis. Mechanistically, gut microbes contribute to tumorigenesis through direct genotoxic effects (e.g., DNA damage), activation of inflammatory pathways, and metabolite-mediated interactions—exhibiting dual roles, as seen with short-chain fatty acids versus secondary bile acids. These processes often interact with host genetic backgrounds, forming complex gene-environment interactions. These findings the potential of microbiota-derived signatures as biomarkers for early detection and prognostic prediction. Furthermore, microbiota-targeted strategies—such as dietary interventions, probiotics, pharmaceuticals, and nanotechnology-based approaches—are being actively explored for precision prevention and treatment of CRC. • Gut microbiota dysbiosis causally linked to colorectal cancer risk. • Microbes drive CRC via genotoxicity, inflammation, and metabolite signaling. • Microbial signatures enable early detection and prognosis prediction. • Microbiota-targeted strategies show promise for precision CRC prevention. • Multi-omics reveal novel microbiome-based biomarkers and therapies.