The gut microbiota: a key modulator of radiotherapy efficacy and toxicity in colorectal cancer

The gut microbiota plays a critical role in modulating both the efficacy and toxicity of radiotherapy in patients with colorectal cancer (CRC). This review synthesizes current evidence on the bidirectional interaction between the gut microbiome and radiotherapy, highlighting the mechanisms through which microbial communities influence radiosensitivity and treatment-related adverse effects. Specific microbiota-derived metabolites, such as short-chain fatty acids and methylglyoxal, can enhance the radiotherapeutic response by exacerbating DNA damage, promoting immunogenic cell death, and activating antitumor immunity. Conversely, dysbiosis may contribute to radioresistance and exacerbate radiation-induced enteritis by impairing intestinal barrier function and amplifying inflammatory responses. Therapeutic strategies targeting the gut microbiome—including probiotics, prebiotics, antibiotics, and fecal microbiota transplantation—show promise in improving radiotherapy outcomes and mitigating toxicity. However, its clinical application remains limited by issues of safety, variability in individual microbiome composition, and lack of standardized protocols. Further high-quality clinical trials are essential to validate these interventions and advance personalized microbial modulation approaches in CRC radiotherapy.