Targeting the gut microbiota with inulin: a novel approach for the management of irradiation- induced colonic fibrosis

Abstract

Background Radiation therapy used to treat pelvic and abdominal tumors can cause acute or chronic radiation enteropathy. Chronic radiation intestinal fibrosis is one of the most common causes of gastrointestinal complaints. Here, we aimed to clarify that the supplement of dietary fiber inulin can alleviate chronic radiation-induced intestinal fibrosis by altering the gut microbiota, and to elucidate the mechanism. Results Inulin supplements have been shown to elevate the abundances of bacterial that produce short-chain fatty acids (SCFAs) and increased fecal concentrations of microbially derived SCFAs. In validation experiment, transplantation of inulin-derived gut microbiota and metabolite alleviated colonic fibrosis in a mouse model of chronic radiation enteropathy. Treatment with inulin-derived gut microbiota metabolites significantly reduced the expression of fibrosis-related genes and collagen synthesis-related genes in the mouse embryonic fibroblast cell line NIH/3T3. In NIH/3T3 cell lines, the use of inulin-derived metabolites also inhibited the expression of genes related to the extracellular matrix synthesis pathway. Conclusions These evidences highlight that inulin might be employed as a safe and effective supplement to fight against chronic radiation intestinal fibrosis. Our finding also provides a novel insight into targeting changes in gut microbiota to treat radiation enteropathy.