Unraveling the bidirectional interplay of the gut microbiota with chemotherapy and radiotherapy in colorectal cancer: from pathogenesis to probiotic interventions

Colorectal cancer remains a leading cause of cancer-related mortality worldwide. While chemotherapy and radiotherapy serve as a cornerstone of treatment, their clinical efficacy is frequently compromised by therapeutic resistance and gastrointestinal toxicity. Accumulating evidence indicates that the gut microbiota is a critical determinant of both treatment response and adverse events. This review describes a closed-loop model in which chemotherapy and radiotherapy disrupt gut microbial homeostasis, whereas microbiota dysbiosis in turn impairs therapeutic efficacy and exacerbates treatment-related toxicity, thereby establishing an interaction between therapy and the gut microbiota. Probiotics are discussed as a microbiota-directed adjuvant strategy. By restoring microecological balance, reinforcing intestinal barrier function, and modulating systemic immunity, these interventions may provide dual benefits by sensitizing tumors to chemotherapy and radiotherapy and mitigating treatment-related toxicity. Overall, clarifying and therapeutically leveraging this microbiota-chemotherapy and radiotherapy interaction may provide a rational avenue to improve the therapeutic index of chemotherapy and radiotherapy. [PubMed and Web of Science, database inception to January 2026].