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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.
Philippe De Timary,Nathalie M Delzenne
Sophie Leclercq,Tiphaine Le Roy,Sonia Furgiuele,Valentin Coste,Laure B Bindels,Quentin Leyrolle,Audrey Neyrinck,Caroline Quoilin,Camille Amadieu,Géraldine Petit,Laurence Dricot,Vanessa Tagliatti,Patrice D Cani,Kristin Verbeke,Jean-Marie Colet,Peter Stärkel,Philippe De Timary,Nathalie M Delzenne