title: Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity.
abstract: Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.
authors.affiliation: Department of Adult Psychiatry, Institute of Neuroscience, Université Catholique de Louvain, B-1200 Brussels, Belgium;
authors.forename: Sophie
authors.initials: S
authors.lastname: Leclercq
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium;
authors.forename: Sébastien
authors.initials: S
authors.lastname: Matamoros
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium; Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), 1300 Wavre, Belgium;
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium;
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.affiliation: Department of Nuclear Medicine, Cliniques Universitaires Saint-Luc, B-1200 Brussels, Belgium;
authors.forename: François
authors.initials: F
authors.lastname: Jamar
authors.affiliation: Laboratory of Hepato- and Gastroenterology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, Belgium;
authors.forename: Peter
authors.initials: P
authors.lastname: Stärkel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders and Leuven Food Science and Nutrition Center, Katholieke Universiteit Leuven, 3000 Leuven, Belgium;
authors.forename: Karen
authors.initials: K
authors.lastname: Windey
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, S-413 45 Gothenburg, Sweden; and.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tremaroli
authors.affiliation: Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, S-413 45 Gothenburg, Sweden; and Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
authors.affiliation: Translational Research Center for Gastrointestinal Disorders and Leuven Food Science and Nutrition Center, Katholieke Universiteit Leuven, 3000 Leuven, Belgium;
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.affiliation: Department of Adult Psychiatry, Institute of Neuroscience, Université Catholique de Louvain, B-1200 Brussels, Belgium; philippe.detimary@uclouvain.be nathalie.delzenne@uclouvain.be.
authors.forename: Philippe
authors.initials: P
authors.lastname: de Timary
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium; philippe.detimary@uclouvain.be nathalie.delzenne@uclouvain.be.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
mesh_terms: D000328:Adult; D000339:Affect; D000437:Alcoholism / Q000150:complications / Q000382:microbiology*; D001007:Anxiety / Q000150:complications; D001644:Bifidobacterium; D001706:Biopsy; D003863:Depression / Q000150:complications; D064806:Dysbiosis / Q000382:microbiology*; D005243:Feces; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D007778:Lactobacillus; D008099:Liver / Q000473:pathology; D008297:Male; D055442:Metabolome; D064307:Microbiota; D008875:Middle Aged; D010539:Permeability; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D055549:Volatile Organic Compounds / Q000032:analysis
chemical_list: D012336:RNA, Ribosomal, 16S; D055549:Volatile Organic Compounds
keywords: alcohol dependence; behavior; gut microbiota; gut permeability; gut–brain axis