Targeting the gut barrier for the treatment of alcoholic liver disease

Alcohol consumption remains one of the predominant causes of liver disease and liver-related death worldwide. Intriguingly, dysregulation of the gut barrier is a key factor promoting the pathogenesis of alcoholic liver disease (ALD). A functional gut barrier, which consists of a mucus layer, an intact epithelial monolayer and mucosal immune cells, supports nutrient absorption and prevents bacterial penetration. Compromised gut barrier function is associated with the progression of ALD. Indeed, alcohol consumption disrupts the gut barrier, increases gut permeability, and induces bacterial translocation both in ALD patients and in experimental models with ALD. Moreover, alcohol consumption also causes enteric dysbiosis with both numerical and proportional perturbations. Here, we review and discuss mechanisms of alcohol-induced gut barrier dysfunction to better understand the contribution of the gut-liver axis to the pathogenesis of ALD. Unfortunately, there is no effectual Food and Drug Administration-approved treatment for any stage of ALD. Therefore, we conclude with a discussion of potential strategies aimed at restoring the gut barrier in ALD. The principle behind antibiotics, prebiotics, probiotics and fecal microbiota transplants is to restore microbial symbiosis and subsequently gut barrier function. Nutrient-based treatments, such as dietary supplementation with zinc, niacin or fatty acids, have been shown to regulate tight junction expression, reduce intestinal inflammation, and prevent endotoxemia as well as liver injury caused by alcohol in experimental settings. Interestingly, saturated fatty acids may also directly control the gut microbiome. In summary, clinical and experimental studies highlight the significance and efficacy of the gut barrier in treating ALD.