title: Administration of probiotic mixture DM#1 ameliorated 5-fluorouracil-induced intestinal mucositis and dysbiosis in rats.
abstract: 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 × 109or 1 × 108colony-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.
  
  
  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.
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China. Electronic address: Vivianmarat@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China. Electronic address: zgwst@126.com.
authors.forename: Jieli
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D064806:Dysbiosis / Q000188:drug therapy*; D005472:Fluorouracil; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D020556:Neutrophil Infiltration; D010539:Permeability; D019936:Probiotics / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D005472:Fluorouracil
keywords: 5-fluorouracil; Intestinal dysbiosis; Intestinal mucositis; Probiotics; Toll-like receptors