Ethanol metabolism and its effects on the intestinal epithelial barrier.

Ethanol is widely consumed and is associated with an increasing global health burden. Several reviews have addressed the effects of ethanol and its oxidative metabolite, acetaldehyde, on the gastrointestinal (GI) tract, focusing on carcinogenic effects or alcoholic liver disease. However, both the oxidative and the nonoxidative metabolites of ethanol can affect the epithelial barrier of the small and large intestines, thereby contributing to GI and liver diseases. This review outlines the possible mechanisms of ethanol metabolism as well as the effects of ethanol and its metabolites on the intestinal barrier. Limited studies in humans and supporting in vitro data have indicated that ethanol as well as mainly acetaldehyde can increase small intestinal permeability. Limited evidence also points to increased colon permeability following exposure to ethanol or acetaldehyde. In vitro studies have provided several mechanisms for disruption of the epithelial barrier, including activation of different cell-signaling pathways, oxidative stress, and remodeling of the cytoskeleton. Modulation via intestinal microbiota, however, should also be considered. In conclusion, ethanol and its metabolites may act additively or even synergistically in vivo. Therefore, in vivo studies investigating the effects of ethanol and its byproducts on permeability of the small and large intestines are warranted.