Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder

被引：114

作者：

Leclercq, Sophie ^{[1
,2
]}

Le Roy, Tiphaine ^{[2
,3
]}

Furgiuele, Sonia ^{[4
]}

Coste, Valentin ^{[2
]}

Bindels, Laure B. ^{[2
]}

Leyrolle, Quentin ^{[2
]}

Neyrinck, Audrey M. ^{[2
]}

Quoilin, Caroline ^{[1
]}

Amadieu, Camille ^{[1
,2
]}

Petit, Geraldine ^{[1
]}

Dricot, Laurence ^{[1
]}

Tagliatti, Vanessa ^{[4
]}

Cani, Patrice D. ^{[2
,3
]}

Verbeke, Kristin ^{[5
]}

Colet, Jean-Marie ^{[4
]}

Starkel, Peter ^{[6
,7
]}

de Timary, Philippe ^{[1
,8
]}

Delzenne, Nathalie M. ^{[2
]}

机构：

[1] Univ Catholique Louvain UCLouvain, Inst Neurosci, B-1200 Brussels, Belgium

[2] Univ Catholique Louvain UCLouvain, Louvain Drug Res Inst, Metab & Nutr Res Grp, B-1200 Brussels, Belgium

[3] Univ Catholique Louvain UCLouvain, Louvain Drug Res Inst, WELBIO Walloon Excellence Life Sci & Biotechnol, B-1200 Brussels, Belgium

[4] UMONS, Lab Human Biol & Toxicol, B-7000 Mons, Belgium

[5] Katholieke Univ Leuven, Translat Res Ctr Gastrointestinal Disorders, B-3000 Leuven, Belgium

[6] Univ Catholique Louvain UCLouvain, Inst Expt & Clin Res, Lab Hepatogastroenterol, B-1200 Brussels, Belgium

[7] Clin Univ St Luc, Dept Hepatogastroenterol, B-1200 Brussels, Belgium

[8] Clin Univ St Luc, Dept Adult Psychiat, B-1200 Brussels, Belgium

来源：

CELL REPORTS | 2020年 / 33卷 / 02期

关键词：

TRAIT EMOTIONAL INTELLIGENCE; PREFRONTAL CORTEX; KETONE-BODIES; INTESTINAL PERMEABILITY; WITHDRAWAL SYNDROME; GENE-EXPRESSION; BRAIN; DEPENDENCE; ETHANOL; MYELINATION;

D O I：

10.1016/j.celrep.2020.108238

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 beta-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.

引用

页数：23

共 95 条

[1] β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms [J].