Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder
Cell Reports. 2020-10-01; 33(2): 108238
DOI: 10.1016/j.celrep.2020.108238
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Leclercq S(1), Le Roy T(2), Furgiuele S(3), Coste V(4), Bindels LB(4), Leyrolle Q(4), Neyrinck AM(4), Quoilin C(5), Amadieu C(1), Petit G(5), Dricot L(5),
Tagliatti V(3), Cani PD(2), Verbeke K(6), Colet JM(3), Stärkel P(7), de Timary P(8), Delzenne NM(9).
Author information:
(1)Institute of Neuroscience, Université catholique de Louvain (UCLouvain), 1200
Brussels, Belgium; Metabolism and Nutrition Research Group, Louvain Drug Research
Institute, Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.
(2)Metabolism and Nutrition Research Group, Louvain Drug Research Institute,
Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium; WELBIO
(Walloon Excellence in Life Sciences and Biotechnology), Louvain Drug Research
Institute, Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.
(3)Laboratory of Human Biology & Toxicology, UMONS, 7000 Mons, Belgium.
(4)Metabolism and Nutrition Research Group, Louvain Drug Research Institute,
Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.
(5)Institute of Neuroscience, Université catholique de Louvain (UCLouvain), 1200
Brussels, Belgium.
(6)Translational Research Center in Gastrointestinal Disorders, KU Leuven, 3000
Leuven, Belgium.
(7)Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical
Research, Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium;
Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, 1200
Brussels, Belgium.
(8)Institute of Neuroscience, Université catholique de Louvain (UCLouvain), 1200
Brussels, Belgium; Department of Adult Psychiatry, Cliniques Universitaires
Saint-Luc, 1200 Brussels, Belgium. Electronic address:
.
(9)Metabolism and Nutrition Research Group, Louvain Drug Research Institute,
Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium. Electronic
address: .
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 that gut dysbiosis is associated with metabolic alterations that affect behavioral (depression, sociability) and neurobiological (myelination, neurotransmission, inflammation) processes involved in alcohol addiction. By transplanting the gut microbiota from AUD patients to mice, we point out that the production of ethanol by specific bacterial genera and the reduction of lipolysis are associated with a lower hepatic synthesis of β-hydroxybutyrate (BHB), which thereby prevents the neuroprotective effect of BHB. We confirm these results in detoxified AUD patients, in which we observe a persisting ethanol production in the feces as well as correlations among low plasma BHB levels and social impairments, depression, or brain white matter alterations.
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement: Declaration of Interests P.D.C. is the inventor of patent applications dealing with the use of A. muciniphila and its components in the context of obesity and related disorders. P.D.C. is co-founder of A-Mansia Biotech SA. The other authors declare no competing interests.