title: Vancomycin pre-treatment impairs tissue healing in experimental colitis: Importance of innate lymphoid cells.
abstract: The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair.
  
  
  
  Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way.
  
  
  
  Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply.
  
  
  
  Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury.
authors.affiliation: Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
authors.forename: Chenwen
authors.initials: C
authors.lastname: Cai
authors.affiliation: Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Jin
authors.affiliation: Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
authors.forename: Dongjuan
authors.initials: D
authors.lastname: Song
authors.affiliation: Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, PR China. Electronic address: zhr346@hotmail.com.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ran
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D053759:Interleukin-23 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014640:Vancomycin / Q000009:adverse effects*; D000097043:Interleukin-22
chemical_list: D016264:Dextran Sulfate; D053759:Interleukin-23; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; D014640:Vancomycin; D000097043:Interleukin-22; C494087:Stat3 protein, mouse
keywords: Commensal; Inflammatory bowel disease; Innate lymphoid cells; Mucosal healing