The role of the gut microbiota in radiation enteritis: from mechanistic insights to therapeutic applications

Radiation enteritis (RE) is a severe adverse reaction after abdominal and pelvic radiotherapy, with a complicated pathogenesis and no effective treatment. Although gut microbiota dysbiosis was reported to play a critical role in RE, related molecular characteristics and intervention strategies have not been extensively summarized. In this review, the mechanisms of RE, including injury to intestinal stem cells, damage to the vascular endothelium, reshaped immune microenvironment, and mucosal barrier dysfunction, are discussed. In addition, radiation-induced gut microbiota dysbiosis is characterized by decreased abundance of beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium bifidum, and increased abundance of detrimental bacteria such as Escherichia-Shigella and Enterococcus. Beneficial and detrimental bacteria affect the development of RE by regulating inflammatory signaling pathways such as NF-κB and JAK/STAT3, and through their metabolites such as bile acids and short-chain fatty acids. Accordingly, several microbiome-targeted therapeutic strategies, including antibiotic administration, dietary interventions, fecal microbiota transplantation, probiotic administration and engineered bacteria, have been developed to mitigate RE. However, some challenges still remain for these therapeutic strategies. The goal of this review is to highlight the crucial role of gut microbiota dysbiosis in the pathogenesis of RE, thereby accelerating the development of individualized microbial therapies against this disease.