UC San Diego scientists have found that chronic alcohol use impairs the guardrails that protect the liver from pathogens, exacerbating the liver damage caused by alcohol.

A Revolutionary Pathway Unveiled: How mAChR4 Activation Protects Against Alcohol-Associated Liver Disease Through Gut Immune Modulation Alcohol-use disorder and its devastating complications, notably alcohol-associated liver disease (ALD), have long stood as formidable challenges in global health. ALD not only ranks among the leading causes of liver transplantation but also contributes substantially to mortality worldwide. Despite major advances in understanding liver pathology, the intricate interplay between the gut and liver—termed the gut–liver axis—remains only partially understood, especially regarding the immune mechanisms guarding against bacterial translocation in the gut during chronic alcohol exposure.

Chronic alcohol use in humans and mice downregulates small intestinal mAChR4 and reduces goblet-cell-associated antigen passage formation, disrupting antimicrobial immunity.