Microbiome-mediated regulation of chemoradiotherapy response.

The gut microbiota critically influences patient responses to chemoradiotherapy through bidirectional interactions with host physiology, modulating both therapeutic efficacy and toxicity. Radiotherapy and chemotherapy disrupt microbial homeostasis, exacerbating intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance treatment response via metabolic reprogramming, DNA repair regulation, and immune activation. Key mechanisms include microbiota-mediated TLR/NF-κB signaling, SCFA-dependent epigenetic modifications, and microbial enhancement of immune checkpoint inhibitors. Clinical interventions such as probiotics, fecal microbiota transplantation, and targeted antibiotics demonstrate potential to mitigate toxicity and overcome resistance. This review summarizes emerging evidence on how microbial dysbiosis induced by radiotherapy and chemotherapy exacerbates intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance chemoradiotherapy response via metabolic reprogramming, DNA repair modulation, and immune activation. These findings underscore the gut microbiota as a critical determinant of chemoradiotherapy precision, offering actionable targets for microbiome-guided therapeutic optimization.