Duodenale implicaties in de pathofysiologie van functionele dyspepsie: Rol van galzouten

Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, characterized by a variety of symptoms localized in the epigastric region. Due to the high human and economic burden, more effective treatment is badly needed. Progress in the understanding of the diverse underlying pathophysiological mechanisms could lead to better treatment through the development of targeted therapy. Our group reported that patients with FD show impaired duodenal integrity, associated with low-grade inflammation (Vanheel H, 2014). The cause of increased permeability and low-grade inflammation is unclear, but altered response to duodenal luminal factors is an important candidate. The aim of this project is to study the role of bile acids (BA) in the pathophysiology of FD. More specifically, we will investigate whether bile acids can impair mucosal integrity and induce low-grade inflammation, thereby provoking visceral hypersensitivity and altered gastric motor control, all contributing to dyspeptic symptom generation. On the other hand, increased duodenal permeability could lead to an increased passage of BA, resulting in visceral hypersensitivity/altered gastric motor control directly or indirectly via low-grade inflammation. This will be studied in a translational research project, using in vitro investigations, animal experiments, as well as studies in healthy volunteers and patients with FD. This research project is divided in three parts: 1. Characterization of duodenal bile acid composition and receptor expression in functional dyspepsia; 2. Analysis of the relationship between bile acids, bacterial translocation and duodenal mucosal integrity in functional dyspepsia; 3. Evaluation of the effect of ursodeoxycholic acid on duodenal permeability, low-grade inflammation, the gut microbiome and meal related sensory motor function in functional dyspepsia. This project will elucidate the role of BA in the pathophysiology of FD and help in understanding the underlying pathogenetic mechanisms, which will lead to a better targeting of treatment in FD patients.status: publishe