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

  1. Nathalie M. Delzenneb,1,2
  1. aDepartment of Adult Psychiatry, Institute of Neuroscience, Université Catholique de Louvain, B-1200 Brussels, Belgium;
  2. bMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium;
  3. cWalloon Excellence in Life Sciences and BIOtechnology (WELBIO), 1300 Wavre, Belgium;
  4. dDepartment of Nuclear Medicine, Cliniques Universitaires Saint-Luc, B-1200 Brussels, Belgium;
  5. eLaboratory of Hepato- and Gastroenterology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, B-1200 Brussels, Belgium;
  6. fTranslational Research Center for Gastrointestinal Disorders and Leuven Food Science and Nutrition Center, Katholieke Universiteit Leuven, 3000 Leuven, Belgium;
  7. gWallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, S-413 45 Gothenburg, Sweden; and
  8. hNovo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

  1. Edited by Leslie Lars Iversen, University of Oxford, Oxford, United Kingdom, and approved September 15, 2014 (received for review August 11, 2014)

Significance

Alcohol-dependent subjects frequently develop emotional symptoms that contribute to the persistence of alcohol drinking. These subjects are also characterized by gastrointestinal disturbances. In this study, we showed that alcohol-dependent subjects with altered intestinal permeability had also altered gut-microbiota composition and activity and remained with high scores of depression, anxiety, and alcohol craving after a short-term detoxification program. These results are consistent with the existence of a gut–brain axis in alcohol dependence, in which the gut microbiota could alter the gut-barrier function and influence behavior in alcohol dependence. Therefore, this study opens a previously unidentified field of research for the treatment and the management of alcohol dependence, targeting the gut microbiota.

Abstract

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.

Footnotes

  • ↵1P.d.T. and N.M.D. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: philippe.detimary{at}uclouvain.be or nathalie.delzenne{at}uclouvain.be.

  • Author contributions: S.L., P.D.C., A.M.N., P.S., F.B., K.V., P.d.T., and N.M.D. designed research; S.L., F.J., and V.T. performed research; F.B. and K.V. contributed new reagents/analytic tools; S.L., S.M., F.J., K.W., V.T., K.V., P.d.T., and N.M.D. analyzed data; and S.L., S.M., K.W., V.T., P.d.T., and N.M.D. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1415174111/-/DCSupplemental.

Freely available online through the PNAS open access option.

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