Gut-liver axis: Pathophysiological concepts and clinical implications

Bidirectional crosstalk along the gut-liver axis controls gastrointestinal health and disease and exploits envi-ronmental and host mediators. Nutrients, microbial antigens, metabolites, and bile acids regulate meta-bolism and immune responses in the gut and liver, which reciprocally shape microbial community structure and function. Perturbation of such host-microbe interactions is observed in a variety of experimental liver diseases and is facilitated by an impaired intestinal barrier, which is fueling hepatic inflammation and disease progression. Clinical evidence describes perturbation of the gut-liver crosstalk in non-alcoholic fatty liver dis-ease, alcoholic liver disease, and primary sclerosing cholangitis. In liver cirrhosis, a common sequela of these diseases, the intestinal microbiota and microbial pathogen-associated molecular patterns constitute liver inflammation and clinical complications, such as hepatic encephalopathy. Understanding the intricate meta-bolic interplay between the gut and liver in health and disease opens an avenue for targeted therapies in the future, which is probed in controlled clinical trials.