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The Gut Microbiota Drives Metabolic Disorders Which Compromise Sociability in Alcoholic Patients

74 Pages Posted: 1 Oct 2019 Sneak Peek Status: Under Review

See all articles by Sophie Leclercq

Sophie Leclercq

Catholic University of Louvain (UCL) - Institute of Neuroscience

Tiphaine Le Roy

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Sonia Furgiuele

Université de Mons-Hainaut - Laboratory of Human Biology & Toxicology

Valentin Coste

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Laure Bindels

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Audrey Neyrinck

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Caroline Quoilin

Catholic University of Louvain (UCL) - Institute of Neuroscience

Camille Amadieu

Catholic University of Louvain (UCL) - Institute of Neuroscience

Vanessa Tagliatti

Université de Mons-Hainaut - Laboratory of Human Biology & Toxicology

Patrice Cani

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Kristin Verbeke

KU Leuven

Jean-Marie Colet

Université de Mons-Hainaut - Laboratory of Human Biology & Toxicology

Peter Stärkel

Catholic University of Louvain (UCL)

Philippe de Timary

Catholic University of Louvain (UCL) - Institute of Neuroscience

Nathalie Delzenne

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

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Abstract

Patients with alcohol use disorder (AUD) present with important emotional, cognitive and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking.  Here, we show for the first time that the gut microbiota drives behavioral features of alcohol addiction including reduced sociability. By transplanting the gut microbiota from AUD patients to mice, we pointed out that the production of ethanol by specific bacterial genera, is associated with a lower hepatic synthesis of beta-hydroxybutyrate (BHB), and thereby prevent the protective effect of BHB on social behavior, neuroinflammation and neurotransmission. We confirmed this hypothesis detoxified AUD patients, in which we observed a persisting ethanol production in the feces as well as correlations between low plasma BHB levels and social impairments. Our data support new pathways involved in behavioral disorders associated with alcohol addiction, that could be considered for future treatments.

Keywords: gut microbiota, gut-brain axis, sociability: metabolomics, ethanol, β-hydroxybutyrate, liver, ketogenic diet, alcoholism, addiction

Suggested Citation

Leclercq, Sophie and Le Roy, Tiphaine and Furgiuele, Sonia and Coste, Valentin and Bindels, Laure and Neyrinck, Audrey and Quoilin, Caroline and Amadieu, Camille and Tagliatti, Vanessa and Cani, Patrice and Verbeke, Kristin and Colet, Jean-Marie and Stärkel, Peter and de Timary, Philippe and Delzenne, Nathalie, The Gut Microbiota Drives Metabolic Disorders Which Compromise Sociability in Alcoholic Patients (September 30, 2019). CELL-METABOLISM-D-19-01083. Available at SSRN: https://ssrn.com/abstract=3461778 or http://dx.doi.org/10.2139/ssrn.3461778
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Sophie Leclercq

Catholic University of Louvain (UCL) - Institute of Neuroscience ( email )

Belgium

Tiphaine Le Roy

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Belgium

Sonia Furgiuele

Université de Mons-Hainaut - Laboratory of Human Biology & Toxicology

Belgium

Valentin Coste

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Belgium

Laure Bindels

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Belgium

Audrey Neyrinck

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Belgium

Caroline Quoilin

Catholic University of Louvain (UCL) - Institute of Neuroscience

Belgium

Camille Amadieu

Catholic University of Louvain (UCL) - Institute of Neuroscience

Belgium

Vanessa Tagliatti

Université de Mons-Hainaut - Laboratory of Human Biology & Toxicology

Belgium

Patrice Cani

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group

Belgium

Kristin Verbeke

KU Leuven

Oude Markt 13
Leuven, Vlaams-Brabant 3000
Belgium

Jean-Marie Colet

Université de Mons-Hainaut - Laboratory of Human Biology & Toxicology

Belgium

Peter Stärkel

Catholic University of Louvain (UCL)

Place Montesquieu, 3
Louvain-la-Neuve, 1348
Belgium

Philippe De Timary

Catholic University of Louvain (UCL) - Institute of Neuroscience

Belgium

Nathalie Delzenne (Contact Author)

Catholic University of Louvain (UCL) - Metabolism and Nutrition Research Group ( email )

Belgium

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