A balanced gut microbiota, is essential for host well-being. Alternations in gut microbial communities were observed in patients suffering from various diseases. Radiation proctitis (RP) is a pathology developed following radiation treatment of pelvic malignancies, including urologic and gynecologic cancers. RP has protean clinical manifestations which account for significant morbidity and poor quality of life. Due to the potential impact of microbiome on radiation-induced tissue damage, in this study we investigated gut microbiota dynamics during the pathogenesis of proctitis and addressed the question on whether microbiota dysbiosis directly affects the disease, or is a result of the altered intestinal environment. Herein, a mouse model of localized rectal irradiation was used to characterized the intestinal flora, at different stages of post-irradiation disease, using fingerprinting and high-throughput approaches, based on fecal samples and colon biopsies. Interestingly, during RP, a shift in gut microbiome was observed, while each clinical stage was represented by a unique microbial signature. These bacterial composition changes were correlated with the disease progression and immunologic parameters, as characterized by colonic cytokine expression, histopathology and macroscopic symptoms of body weight, diarrhea and rectal bleeding. The RP-induced microbiome was found to have clear inflammatory effect on epithelial cells in co-culture experiments, and gut bacteria of healthy mice had positive effect on cell cultures, a finding of potential clinical relevance for RP patients. Our study provides valuable information concerning the impact of the altered microbiota on controlling disease severity and may suggest potential manipulation of the microbiota in a clinically beneficial manner.
