We aim to define contributions of genetics, gut microbiome and environmental factors, including diet, to risk for development of (age-related) liver and cardiometabolic diseases. We focus on identification of liver/gut-derived metabolites involved in disease development by interference with nutrient sensing, cellular senescence and inflammageing, the latter defined as a non-resolving, low-grade, chronic inflammation process that progresses with age and is harmful to health. The group has a long tradition in deciphering the (patho)physiological roles of bile acids, acting both as biological detergents and as signalling molecules, in health and disease
The proposed project aims to determine the contributions of specific bile acids and their metabolites in the maintenance of intestinal barrier function, known to deteriorate during ageing and, as a consequence, to contribute to inflammageing. Major focus will be on characterizing mechanisms that determine development of a “leaky gut” during natural and accelerated ageing. The project will use (partly humanized) mouse models as well as cellular systems and advanced analytical/bioinformatics approaches.