FIGURE 4.

Alcohol and the gut-liver axis

Alcohol abuse produces marked alterations in the gastrointestinal tract. Esophageal and gastric dysmotility facilitate acid regurgitation and contribute to postemetic lacerations of the distal esophagus induced by vomiting (Mallory-Weiss Syndrome). Liver fibrosis and the resulting intrahepatic pressure increase leads to development of esophageal varicosities. Alcohol promotes chronic gastritis followed by decreased mucosal thickness and atrophy during the chronic phase. Chronic alcohol abuse impairs intestinal essential amino acid and vitamin absorption. In the liver, alcohol metabolism increases the production of ROS and lowers antioxidant levels, which contributes to liver injury. ROS generation leads to lipid peroxidation, alterations in plasma and intracellular membranes, and release of proinflammatory and profibrotic mediators. Alcohol and its metabolites disrupt intestinal barrier function by affecting the integrity of tight junctions, promoting the dissociation and redistributing proteins like ZO-1, claudin, and occludin. Increased paracellular permeability leads to increased bacterial toxin translocation from the gut lumen and disseminated to the systemic circulation via the portal vein and the lymphatic route. This later route of dissemination may be significant, since alcohol intoxication has been shown to promote lymphatic pumping. GSH, reduced glutathione; ROS, reactive oxygen species; HCV, hepatitis C virus; LES, lower esophageal sphincter. The potential clinical consequences of alcohol abuse and its impact on the endocrine system are shown in the box.