Novel insights in the pathophysiology and management of functional dyspepsia

Functional dyspepsia is a common functional gastrointestinal disorder with bothersome symptoms in the upper abdomen without an organic lesion that is likely to explain the complaints. Traditionally, changes in gastric physiology were held responsible for the symptoms, including delayed gastric emptying, impaired gastric accommodation and hypersensitivity to distension. However, gastric sensorimotor disturbances correlated only poorly to symptom severity and treatments targeting these abnormalities are not very effective. In the last decade, the duodenum has been identified as a key integrator in the pathophysiology of functional dyspepsia with an impaired barrier function and immune activation with a particular role for eosinophils and mast cells. Moreover, changes in the duodenal microbiota were associated to dyspeptic symptoms and eosinophil counts. PPIs – still the first line treatment for functional dyspepsia – have been shown to reduce symptoms through anti-inflammatory effects in the duodenum, similar to their effect in eosinophilic esophagitis. Finally, specific probiotic strains were effective in improvement of postprandial symptoms, most likely through an anti-inflammatory effect as demonstrated by reduced Th17 signaling. These novel insights in pathophysiology and treatment provide novel hope for patients with this challenging condition.

Keywords: functional dyspepsia, intestinal permeability, duodenum, eosinophil, mast cell, probiotic.