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Gut microbiota and nuclear receptors in bile acid and lipid metabolism

Bile acids, more than soaps
PhD ceremony:Ms C. (Carolien) Out
When:November 26, 2014
Supervisors:A.K. (Bert) Groen, prof. dr. H.J. (Henkjan) Verkade
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Gut microbiota and nuclear receptors in bile acid and lipid

The term ‘metabolic syndrome’ refers to the combination of obesity, hypertension, dyslipidemia and insulin resistance. People with metabolic syndrome have an increased risk to develop cardiovascular disease and type 2 diabetes. Strategies to prevent and treat these metabolic derangements are therefore urgently needed. Therefore, a better understanding of the regulation of inter- and intra-organ metabolic pathways is of key relevance.

Bile acids are produced by the liver, stored in the gallbladder, and released into the intestine after a meal. Bile acids are detergents and essential for intestinal absorption of lipids. Recently it was shown that bile acids also bind to several receptors. As a result they influence the 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. The development of drugs targeted to this receptor could 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.