FOOD-INDUCED DUODENAL IMMUNE ACTIVATION: SYMPTOM TRIGGER AND THERAPEUTIC TARGET IN FUNCTIONAL DYSPEPSIA

Functional dyspepsia (FD) affects 7.2% of the adult population and has a significant impact on quality of life.

Patients present with symptoms in the epigastrium, which include early satiation, postprandial fullness and epigastric pain or burning. Routine investigations including endoscopy are macroscopically normal.

Gastric abnormalities, including delayed emptying, gastric hypersensitivity and impaired accommodation, have been implicated in symptom generation. Current treatment options target gastric function, but have limited efficacy.

Recent studies have shown low-grade duodenal inflammation characterized by eosinophil and mast cell influx and impaired mucosal integrity in FD.

We will investigate the link between duodenal immune activation on the one hand and gastric sensorimotor dysfunction and symptoms on the other hand.

We will provide proof of concept for the pivotal role of mast cells through a controlled trial with palmitoyletahnolamide, an endogenous mast cell stabilizing agent with lower levels in FD.

We hypothesize that food is the trigger for activation of mast cells through a non-IgE-dependent pathway in the presence of impaired duodenal mucosal integrity.

This will be studied in a sham-controlled dietary elimination trial of trigger nutrients, identified by duodenal confocal laser endomicroscopic evaluation of food allergies. If confirmed, our project will reshape the disease concept and management in this prevalent condition.