Targeting gut inflammation inhibits alcohol-induced liver disease

Abstract Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during alcohol intake and is a functional regulator of alcohol-related liver injury that can be exploited therapeutically. Alcohol intake induces a chronic phenotypic pro-inflammatory shift in immune cell populations in gut lamina propria and results in the disruption of intestinal barrier. Treatment of wild-type C57BL/6 mice with the local gut anti-inflammatory, mesalamine, decreases alcohol-induced liver injury, reverses gut inflammation and improves metabolic parameters. Mesalamine reduced gut permeability and endotoxemia, increased IgA secretion and is associated with reduced Akt activation and P-b-catenin levels in the ileum and large intestine. These beneficial effects are dependent on adaptive and gut immunity. Thus, targeting gut inflammation with mesalamine represents a novel treatment approach for alcoholic liver disease.