Bile and bugs Unraveling the postprandial response of bile acids and gut microbiota in (inherited) metabolic diseases

Current thesis aims to investigate the intricate relationship between bile acids (BAs) and the gut microbiota within the context of postprandial physiology. BAs, essential for fat digestion and absorption, also function as critical signaling molecules regulating postprandial processes, including bile acid synthesis, glucose, lipid, and energy metabolism. This regulation is mediated through the activation of specific receptors, such as the Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), located in various tissues, including the intestines, liver, and adipose tissue. The gut microbiota, crucial for nutrient absorption, also actively participate in the intestinal conversion of BAs. These metabolic transformations generate metabolites that influence FXR and TGR5 receptor activity, thereby modulating the postprandial response. Considering the shared pivotal role of BAs and the gut microbiota in postprandial nutrient absorption, a strong association between the two is evident.
Part 1 provides an overview of postprandial processes, their measurement, and foundational knowledge of BAs and the gut microbiota. Part 2 presents an in-depth literature review exploring the relationship between BAs and the gut microbiota. Part 3 encompasses two observational studies investigating the impact of aging and cerebrotendinous xanthomatosis (CTX) on the postprandial response. Part 4 focuses on two interventions utilizing a secondary conjugated bile acid (gDCA). Finally, Part 5 examines the potential of lifestyle interventions to influence postprandial processes in individuals with metabolic syndrome.