title: Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.
abstract: The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio ofFirmicutestoBacteroidetesInterestingly, administration of bile acids prevented the loss ofClostridiumcluster XIVa and increased the abundance ofAkkermansia muciniphila, bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD.IMPORTANCESecondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we studied the alterations in the fecal microbial abundance in colitic mice following the administration of secondary bile acids. Our results show that secondary bile acids reduce the severity of colitis and ameliorate colitis-associated fecal dysbiosis at the phylum level. This study indicates that secondary bile acids might act as a safe and effective drug for inflammatory bowel disease.
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Van den Bossche
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Hindryckx
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Devisscher
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Devriese
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Welden
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Holvoet
authors.affiliation: Center for Microbial Ecology and Technology, Ghent University, Ghent, Belgium.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Vilchez-Vargas
authors.affiliation: Microbial Interactions and Processes Research Group, Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Vital
authors.affiliation: Microbial Interactions and Processes Research Group, Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Dietmar H
authors.initials: DH
authors.lastname: Pieper
authors.affiliation: Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Vanden Bussche
authors.affiliation: Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
authors.forename: Lynn
authors.initials: L
authors.lastname: Vanhaecke
authors.affiliation: Center for Microbial Ecology and Technology, Ghent University, Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Wiele
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: De Vos
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium debby.laukens@ugent.be.
authors.forename: Debby
authors.initials: D
authors.lastname: Laukens
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000187:drug effects; D003106:Colon / Q000382:microbiology; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000188:drug therapy*; D005243:Feces / Q000382:microbiology; D000068536:Bacillota / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D051379:Mice; D013654:Taurine / Q000737:chemistry; D013655:Taurochenodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D013654:Taurine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C024033:glycoursodeoxycholic acid; D014580:Ursodeoxycholic Acid; D016264:Dextran Sulfate
keywords: bile acids; colitis; dysbiosis