Intestinal dysbiosis and permeability: the yin and yang in alcohol dependence and alcoholic liver disease

Author:

Stärkel Peter12,Leclercq Sophie34,de Timary Philippe35,Schnabl Bernd67

Affiliation:

1. Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium

2. Department of Hepato-Gastroenterology, Cliniques Universitaires St. Luc, Brussels, Belgium

3. Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium

4. Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium

5. Department of Adult Psychiatry, Cliniques Universitaires St. Luc, Brussels, Belgium

6. Department of Medicine, University of California San Diego, La Jolla, CA, U.S.A.

7. Department of Medicine, VA San Diego Healthcare System, San Diego, CA, U.S.A.

Abstract

Alcohol dependence and alcoholic liver disease represent a major public health problem with substantial morbidity and mortality. By yet incompletely understood mechanisms, chronic alcohol abuse is associated with increased intestinal permeability and alterations of the gut microbiota composition, allowing bacterial components, bacteria, and metabolites to reach the portal and the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in remote organs such as the liver leading to the release of pro-inflammatory cytokines which are considered important mediators of the liver–gut–brain communication. Although circulating cytokines are likely not the sole factors involved, they can induce liver inflammation/damage and reach the central nervous system where they favor neuroinflammation which is associated with change in mood, cognition, and drinking behavior. In this review, the authors focus on the current evidence describing the changes that occur in the intestinal microbiota with chronic alcohol consumption in conjunction with intestinal barrier breakdown and inflammatory changes sustaining the concept of a gut–liver–brain axis in the pathophysiology of alcohol dependence and alcoholic liver disease.

Publisher

Portland Press Ltd.

Subject

General Medicine

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