Direct liver cell damage by alcohol has been well established as one of the primary causes of liver disease. Recent work by scientists at UC San Diego demonstrates that, in addition, alcohol can lead to liver disease by causing an imbalance in the gut microflora. Humans produce two natural broad-spectrum antimicrobial proteins called REG3B and REG3G that surveil gut mucosal bacteria and prevent overgrowth. Alcohol causes a down-regulation in the genes encoding for REG3B and REG3G leading to bacterial overgrowth, an increase in microbial translocation, immune activation and further cell damage, including the liver. Mice with REG3B/REG3G knockouts have more severe liver disease while mice with REG3G over-expression avoid liver damage. This work adds to the increasing importance of gut health on a wide range of disease.