Proton pump inhibitors reduce duodenal eosinophilia, mast cells and permeability in patients with functional dyspepsia.

BACKGROUND & AIMS Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPI) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI-therapy in FD patients and healthy volunteers (HV). METHODS We performed a prospective interventional study assessing symptoms (PAGI-SYM), duodenal alterations and systemic factors in FD patients ("FD-starters") and HV before and after PPI-therapy (pantoprazole 40mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells and permeability were quantified. Luminal pH and bile salts were determined in duodenal aspirates. Procedures were also performed in PPI-refractory FD patients ("FD-stoppers") before and 8 weeks after PPI-withdrawal. Between- and within-group changes from baseline and associations with duodenal or systemic factors were analyzed using linear mixed models. RESULTS The study was completed by 30 HV, 27 FD-starters and 18 FD-stoppers. Symptoms and duodenal eosinophils, mast cells (all P < .0001), and paracellular passage (P = .02) were significantly higher in FD-starters vs. HV, and reduced with PPI-therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off-PPI. In contrast, immune cells and permeability increased in HV on-PPI. Dyspeptic symptoms correlated with eosinophils before and during PPI-therapy, while increased eosinophils and permeability in HV on-PPI were associated with changes in bile salts. CONCLUSIONS We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPI in FD, with differential effects in HV pointing to a role of luminal changes.