title: Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) can cause significant small bowel injuries. The role of gut microbiota in this NSAID-induced enteropathy is poorly understood. We studied the dynamic changes in gut microbiota following indomethacin administration in mice, and investigated the effects of these adaptive changes on subsequent NSAID-induced enteropathy. The changes in gut microbiota were studied using 16S rRNA sequencing, and the effects of such changes were investigated using antibiotics and a faecal transplantation model. After indomethacin treatment, significant adaptive changes in gut microbiota were observed, including increased abundance of Firmicutes and decreased abundance in that of Bacteroidetes. Depletion of gut microbiota with antibiotics led to a higher mortality (P = 0.0021) in mice compared to controls. Mice pre-transplanted with adaptively changed microbiota showed less small bowel injury and lower levels of pro-inflammatory cytokines when exposed to indomethacin. In summary, this study identifies adaptive changes in the gut microbiota upon indomethacin administration, which can in turn ameliorate further NSAID-induced injury. The heightened mortality with antibiotic depletion of the adaptively changed microbiota suggests its important role in protecting against such injury. This study provides insight for future efforts to target the microbiota as a therapeutic strategy.
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.|Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.|Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Geicho
authors.initials: G
authors.lastname: Nakatsu
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Sunny
authors.initials: S
authors.lastname: Wong
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.|Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
authors.forename: James Y W
authors.initials: JY
authors.lastname: Lau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000235:genetics; D007213:Indomethacin; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000382:microbiology* / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D007213:Indomethacin