Targeting intestinal dysbiosis in alcoholic liver disease

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Bernd Schnabl
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
The intestinal microbiota and the human body have a symbiotic relationship. A dysbalance of this delicate homeostasis between host and microbes can lead to disease. Alcoholic liver disease is associated with changes in the gut microbiota. Alcohol-associated intestinal dysbiosis is characterized by bacterial overgrowth and changes in the microbial composition. In addition, alcohol abuse results in an intestinal barrier dysfunction. The integrity of the gut barrier is of specific importance to limit bacteria and bacterial products from translocating and reaching extraintestinal sites. The intestinal epithelium has the capacity to segregate microorganisms from the host. A dysfunctional intestinal barrier allows bacterial products to translocate to the portal circulation and reach the liver. This translocation process induces an inflammatory response in the liver and aggravates liver disease. Dysbiosis can induce a failure of the intestinal barrier leading to pathological bacterial translocation and the initiation of an inflammatory response in the liver. The mucosa-associated microbiota has been linked to translocation of viable bacteria through intestinal epithelial cells (transcytosis) to extraintestinal spaces and organs. Recent preclinical studies emphasized the importance of intestinal inflammation for the onset of gut barrier disruption and microbial translocation. Dietary approaches to restore levels of saturated fatty acids in the intestine, maintained eubiosis, stabilized the gut barrier and reduced alcoholic liver disease. In conclusion, the gut microbiota represents an excellent target to prevent the onset and progression of alcoholic liver disease.