Pectin alleviates alcohol-associated liver disease partly through cell-type-specific aryl hydrocarbon receptor signaling in female mice

The aryl hydrocarbon receptor (AhR) plays a critical role in alcohol-associated liver disease (ALD). Pectin improves ALD partially through the AhR pathway. However, AhR is expressed across different organs and cell types, and the specific cellular targets mediating AhR's effects in ALD remain unclear. We generated conditional AhR knockout mice in intestinal epithelial cells, hepatocytes, dendritic cells, and Rorγt-positive cells, in which AhR may play a critical role in regulating the gut-liver axis and pectin protection against ALD. ALD was induced using the Lieber-DeCarli model, and mice received pectin supplementation. AhR deficiency in intestinal epithelial cells and hepatocytes in mice leads to increased hepatic inflammation and serum ALT following alcohol administration compared with their littermate controls. However, pectin exerted strong protective effects against ALD in all the models. Our results suggest that AhR activation across multiple cell types, rather than a single cell type, mediates the protective role of pectin.