Review of gut microbiota and colorectal cancer highlights unresolved causality and clinical translation challenges

The gut microbiota has received considerable attention in the field of colorectal cancer (CRC) research in recent years. In this review, we have explored the multifaceted relationship between the gut microbiota and CRC progression and treatment. The composition, distribution, and normal physiological functions of the gut microbiota have been summarized, along with the association between gut dysbiosis and CRC based on the body of evidence from animal experiments and clinical studies. In addition, we have discussed the mechanisms through which specific microbial configurations or microbiota-derived metabolites may contribute to colorectal carcinogenesis, including genotoxic effects, inflammation, and immune dysregulation. The impact of the gut microbiota on the efficacy of chemotherapy, radiotherapy, and immunotherapy, and new treatment strategies based on the gut microbiota, such as probiotic intervention, prebiotic application, and fecal microbiota transplantation have also been explored. Despite some promising outcomes, the specific carcinogenic microorganisms have not been identified, and it is challenging to distinguish association from causation, determine the influence of individual differences, and translate the research to clinical applications. In the future, more rigorous longitudinal studies, gnotobiotic models with defined microbial communities, and mechanistic interventional studies are needed to strengthen causal inference, and provide practical guidance for CRC prevention and treatment. Beyond summarizing reported associations, this review proposes a microbiota-immune-metabolism-therapy axis by integrating tumorigenic mechanisms, immune contexture, and treatment responsiveness into a single translational framework.