Gut microbiota and nuclear receptors in bile acid and lipid metabolism: bile acids, more than soaps

Metabolic syndrome refers to the combination of obesity, hypertension, dyslipidemia and insulin resistance. Metabolic syndrome increases the chance on cardiovascular disease and type 2 diabetes. Strategies to prevent and treat these metabolic derangements are therefore urgently needed. For this purpose better insight in the regulation of inter- and intra-organ metabolic pathways is of key relevance. Bile acids are produced by the liver, are stored in the gallbladder and are released into the intestine upon a meal. Bile acids are essential detergents required for the intestinal absorption of lipids. Recently it was shown that bile acids can also bind to several receptors. Hereby they can influence bile acid, lipid and glucose metabolism. In this thesis we investigated the receptor Lrh1. We show that this receptor is involved in the regulation of bile acid and lipid metabolism. Development of drugs targeted to this receptor could in the future potentially influence bile acid and lipid metabolism and aid to combat dyslipidemia and associated diseases. An increasing level of evidence reveals that gut microbiota are also associated with metabolic diseases. In mice and men we investigated to role of gut microbiota in bile acid and glucose metabolism. We found that gut microbiota influence the absorption of bile acids in the intestine. Moreover, a decrease in certain bacterial species after antibiotic treatment coincided with worsened glucose control in obese subjects. These findings emphasize the importance of a balanced gut flora and offer applicable ways to prevent or counteract metabolic diseases in the future