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

Cell Rep. 2020 Oct 13;33(2):108238. doi: 10.1016/j.celrep.2020.108238.


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.

Keywords: alcohol use disorder; depression; gut microbiota; gut-brain axis; ketogenic diet; metabolomics; sociability; β-hydroxybutyrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • 3-Hydroxybutyric Acid / metabolism*
  • Alcoholism / blood
  • Alcoholism / complications*
  • Alcoholism / microbiology*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Behavior, Animal / drug effects
  • Brain / physiopathology
  • Depression / blood
  • Depression / complications*
  • Depression / microbiology*
  • Diet, Ketogenic
  • Dysbiosis / blood
  • Dysbiosis / complications
  • Dysbiosis / microbiology
  • Ethanol
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome* / drug effects
  • Homeostasis / drug effects
  • Humans
  • Inflammation / blood
  • Inflammation / complications
  • Intestines / drug effects
  • Intestines / pathology
  • Lipolysis / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Metabolic Networks and Pathways / drug effects
  • Mice, Inbred C57BL
  • Myelin Sheath / metabolism
  • Permeability
  • Social Behavior*
  • Tissue Donors


  • Anti-Bacterial Agents
  • Ethanol
  • 3-Hydroxybutyric Acid