The liver is structurally and functionally positioned as a filter and homeostatic guardian between the gut and the rest of the body. The liver drains gut-derived compounds via the portal tract, has important tolerogenic and detoxifying functions, controls glucose levels and lipid metabolism and excretes bile acids via the biliary tree to complete the enterohepatic cycle. This cycle is important as it is also involved in the pharmacological effect of drugs and metabolites. Unsurprisingly, the liver-gut axis is compromised in many gastrointestinal diseases.
In the Hepatology Research Unit, we focus on chronic liver diseases (CLDs) including (non-) alcoholic fatty liver disease, cholestatic liver disease, liver fibrosis and hepatocellular carcinoma which are all characterized by a leaky-gut and intestinal microbial dysbiosis. As a consequence, the liver immune system is chronically activated by gut-derived bacterial compounds and this results in chronic hepatic inflammation. Chronic inflammation in the liver induces pathological vessel and scar formation and results in associated complications such as portal hypertension which compromise the liver-gut cross-talk. As such, patients with CLD are at increased risk for bacterial translocation and sepsis. Altering intestinal microbiota, the bile acid pool and intestinal motility have all become explorative novel therapeutic strategies in patients suffering from CLD but despite this, effective therapy is lacking. In the Hepatology Research Unit, we use mouse models, human samples and in vitro assays to study the pathogenesis of liver diseases and explore new therapeutic opportunities which target inflammation and angiogenesis and how these compounds restore glucose and lipid metabolism and the liver-gut symbiosis.