The central role of the duodenal microenvironment in functional dyspepsia

Functional dyspepsia is a common gastrointestinal disorder, characterized by upper abdominal symptoms in the absence of a clear organic cause. Nevertheless, the pathophysiology is still unclear and the available treatment options are limited and poorly efficacious. In the recent years, several groups, including our own, have demonstrated increased permeability of the duodenal mucosa and increased presence of eosinophils and mast cells in the duodenum. However, the cause of the duodenal immune activation and its relevance to symptom generation are still unknown. In the current project we will first provide a detailed characterization of the mucosal immune activation by flow cytometry of lamina propria leukocytes and measurement of local cytokine profiles. We will also investigate whether these local or systemic (plasma and feces) signs of immune activation can be used as a biomarker. We will study the role of locally produced soluble mediators and luminal factors in this inflammatory response. Treatment studies investigating the anti-inflammatory mechanism and clinical effect of the locally active corticosteroid budesonide, will be undertaken.