Administration of probiotic mixture DM#1 ameliorated 5-fluorouracil-induced intestinal mucositis and dysbiosis in rats

Objective: The use of probiotics to alleviate chemotherapy-induced intestinal mucositis is supported by clinical consensus. However, no studies to date, to our knowledge, have systematically analyzed the effects of a probiotic mixture on chemotherapy-induced mucositis or assessed changes in the intestinal microbiota after probiotic treatment. The aim of this study was to report the effects of a probiotic mixture, DM#1, on intestinal mucositis and dysbiosis of rats treated with 5-fluorouracil (5-FU). Methods: Twenty-eight male Sprague Dawley rats weighing 180 to 220 g were randomly divided into four groups: control, 5-FU, probiotic high (PH), and probiotic low (PL). Except for the control group, all other groups received intraperitoneal injections of 5-FU for 5 d, and the PH and PL groups received DM#1 intragastrically (1 x 10(9) or 1 x 10(8) colony-forming units/kg, respectively) for 8 d. One day after the last administration, rats were sacrificed and the ilea were removed for histopathologic assessment and evaluation of permeability, myeloperoxidase activity, levels of cytokines (interleukin [IL]-4, IL-6, tumor necrosis factor [TNF]-alpha), and mRNA of toll-like receptors (TLR; TLR2, TLR4, and TLR9). Additionally, intestinal microbiota profiles were analyzed by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis and quantitative real-time PCR. Results: Treatment with DM#1 ameliorated 5-FU-induced intestinal mucosal injury in rats, possibly by reducing proinflammatory cytokine levels and neutrophil infiltration. The increased intestinal permeability caused by 5-FU was ameliorated. These results were closely associated with the reestablishment of intestinal microbial homeostasis and alteration of the TLR2/TLR4 signaling pathway. Conclusions: Administration of the probiotic mixture DM#1 ameliorated 5-FU-induced intestinal mucositis and dysbiosis in rats.