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 pathophysiology functional dyspepsia (FD), effect and mechanism proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied systemic relation to PPI patients with FD healthy volunteers (HVs). Methods performed a prospective interventional study assessing symptoms (Patient Assessment Gastrointestinal Symptom Severity Index), alterations, factors (“FD-starters”) HVs before after (pantoprazole 40 mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells permeability were quantified. Luminal pH bile salts determined aspirates. Procedures also PPI-refractory (“FD-stoppers”) 8 weeks withdrawal. Between- within-group changes from baseline associations analyzed using linear mixed models. Results The was completed by 30 HV, 27 FD-starters, 18 FD-stoppers. Symptoms (all, P < .0001), paracellular passage (P = .02) significantly higher FD-starters vs reduced therapy. immune decreased FD-stoppers off PPIs. In contrast, increased on Dyspeptic correlated eosinophils during therapy, PPIs associated salts. Conclusions provide first evidence eosinophil-reducing effects as therapeutic FD, differential pointing role luminal changes. ClinicalTrials.gov, Number: NCT03545243.