Journal Article

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

Deng, Ying, Li, Ming, Yuan, Jieli, Huang, Ziyi, Wang, Fengjiao, Dong, Weiwei, Tang, Yan, Wu, Yingtao

2017

Overview

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). 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 × 109 or 1 × 108 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]-α), 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. 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. Administration of the probiotic mixture DM#1 ameliorated 5-FU–induced intestinal mucositis and dysbiosis in rats. •Administration of probiotic mixture DM#1 ameliorated 5-fluorouracil–induced mucositis and dysbiosis in rats.•Administration of DM#1 promoted reestablishment of intestinal microbial homeostasis.•Administration of DM#1 also altered the toll-like receptor 2 signaling pathway.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: 5-fluorouracil / Animals / Bacteria / Chemotherapy / Cytokines / Cytokines - metabolism / dysbiosis / Dysbiosis - drug therapy / enzyme activity / Experiments / Fluorouracil / Gastroenterology and Hepatology / Gastrointestinal Microbiome - drug effects / gel electrophoresis / histopathology / Homeostasis / ileum / Ileum - drug effects / Ileum - metabolism / Ileum - pathology / Inflammation - metabolism / Interleukin-4 - metabolism / interleukin-6 / Interleukin-6 - metabolism / Intestinal dysbiosis / intestinal microorganisms / Intestinal Mucosa - drug effects / Intestinal Mucosa - metabolism / Intestinal Mucosa - pathology / Intestinal mucositis / Kinases / laboratory animals / Male / males / messenger RNA / Mucositis - chemically induced / Mucositis - drug therapy / Mucositis - metabolism / myeloperoxidase / Neutrophil Infiltration / neutrophils / Permeability / polymerase chain reaction / Probiotics / Probiotics - therapeutic use / Random Allocation / rats / Rats, Sprague-Dawley / RNA, Messenger - metabolism / Rodents / Signal Transduction / Small intestine / Studies / Toll-like receptor 2 / Toll-Like Receptor 2 - genetics / Toll-Like Receptor 2 - metabolism / Toll-like receptor 4 / Toll-Like Receptor 4 - genetics / Toll-Like Receptor 4 - metabolism / Toll-like receptor 9 / Toll-Like Receptors / Tumor Necrosis Factor-alpha - metabolism / tumor necrosis factors