From Host-Microbiome Symbiosis to Clinical Translation: A Gut Microbiome Perspective on Radiation Enteritis

Radiotherapy is an essential component of multimodal treatment for solid tumors, and more than half of patients with cancer receive radiation during their disease course. Because of the unique anatomical and physiological features of the intestine, radiation enteritis (RE) remains a common and clinically challenging complication of abdominal and pelvic irradiation, with limited effective treatment options. In this review, we re-examine RE from a host-microbiome perspective. We summarize classical pathophysiological mechanisms and discuss how radiotherapy reshapes gut microbial composition and metabolism. We also highlight the roles of microbial metabolites, including short-chain fatty acids, bile acids and tryptophan derivatives, in barrier repair, immune homeostasis and stem-cell regeneration. Finally, we discuss microbiome heterogeneity across disease phases, tumor types and host factors, as well as microbiota-mediated gut-brain, gut-cardiopulmonary, gut-skin and gut-bone-marrow axes involved in systemic radiation injury. We further outline microbiome-based strategies for individualized risk stratification and early prediction, and recent advances and limitations of probiotics and synbiotics, fecal microbiota transplantation, dietary and lifestyle interventions, drugs and natural products, engineered microbes and novel delivery systems, highlighting the gut microbiome as a promising entry point to improve prevention and treatment of RE and systemic radiation toxicity.