Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity

Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4485-93. doi: 10.1073/pnas.1415174111. Epub 2014 Oct 6.


Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.

Keywords: alcohol dependence; behavior; gut microbiota; gut permeability; gut–brain axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect
  • Alcoholism / complications
  • Alcoholism / microbiology*
  • Anxiety / complications
  • Bifidobacterium
  • Biopsy
  • Depression / complications
  • Dysbiosis / microbiology*
  • Feces
  • Female
  • Gastrointestinal Tract / microbiology*
  • Humans
  • Intestines / microbiology*
  • Lactobacillus
  • Liver / pathology
  • Male
  • Metabolome
  • Microbiota
  • Middle Aged
  • Permeability*
  • RNA, Ribosomal, 16S / analysis
  • Volatile Organic Compounds / analysis


  • RNA, Ribosomal, 16S
  • Volatile Organic Compounds