title: A role for the peripheral immune system in the development of alcohol use disorders?
abstract: Preclinical studies have largely supported that alcohol-consumption induces the development of an important neuro-inflammation and this neuro-inflammation contributes to alcohol-drinking behaviors, notably through TLR4 and LPS related mechanisms. The neuro-inflammation originates from a direct interaction of ethanol with the neuronal and immune brain cells, but also from the generation of an inflammation at the periphery. Ethanol in particular interacts with the intestine to develop a gut dysbiosis and an increase in gut permeability, that allows the liberation of bacterial fragments to the systemic circulation and induces a pro-inflammatory response in the systemic circulation and peripheral organs, and in particular the liver. Peripheral cytokines or activated peripheral cells may cross the blood-brain barrier and activate neuro-inflammation. In humans, peripheral inflammation and intestinal dysbiosis are related to symptoms of alcohol use disorders (AUD), such as depression, anxiety and alcohol-craving, However, the dysbiosis, could also participate in a different manner to the symptomatology of the addiction, possibly by interacting with the stress system, by interfering with the sleep processes and altering the abilities for social interactions. The role of the gut suggests that interventions with probiotics or prebiotics might in the future be of interest for the treatment of the addiction. This article is part of the Special Issue entitled "Alcoholism".
authors.affiliation: Institute of Neuroscience, Université Catholique de Louvain, Avenue Hippocrate 10, B-1200 Brussels, Belgium; Department of Adult Psychiatry, Clinique Universitaire Saint Luc, Avenue Hippocrate 10, B-1200 Brussels, Belgium. Electronic address: philippe.detimary@uclouvain.be.
authors.forename: Philippe
authors.initials: P
authors.lastname: de Timary
authors.affiliation: Department of Hepato-Gastroenterology and Clinique Universitaire Saint Luc and Institute of Clinical Research, Université Catholique de Louvain, Avenue Hippocrate 10, B-1200 Brussels, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Stärkel
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
authors.affiliation: Institute of Neuroscience, Université Catholique de Louvain, Avenue Hippocrate 10, B-1200 Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Leclercq
mesh_terms: D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000503:physiopathology*; D064806:Dysbiosis / Q000276:immunology; D000431:Ethanol / Q000009:adverse effects; D005759:Gastroenteritis / Q000276:immunology; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007249:Inflammation / Q000276:immunology*; D007422:Intestines / Q000276:immunology* / Q000503:physiopathology
chemical_list: D000431:Ethanol
keywords: Alcohol use disorders; Cytokines; Gut-barrier function; Leaky-gut; Lipopolysaccharides; Microbiota; Peptidoglycans; Prebiotics; Probiotics