Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia

Gastroenterology. 2021 Apr;160(5):1521-1531.e9. doi: 10.1053/j.gastro.2020.12.016. Epub 2020 Dec 18.


Background & aims: Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs).

Methods: We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg 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 patients with FD ("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 HVs and reduced with PPI therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off PPIs. In contrast, immune cells and permeability increased in HVs on PPIs. Dyspeptic symptoms correlated with eosinophils before and during PPI therapy, and increased eosinophils and permeability in HVs on PPIs were associated with changes in bile salts.

Conclusions: We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPIs in FD, with differential effects in HVs pointing to a role of luminal changes., Number: NCT03545243.

Keywords: Functional Dyspepsia; Inflammation; Permeability; Proton Pump Inhibitor.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Belgium
  • Bile Acids and Salts / metabolism
  • Case-Control Studies
  • Duodenal Diseases / diagnosis
  • Duodenal Diseases / drug therapy*
  • Duodenal Diseases / immunology
  • Duodenal Diseases / metabolism
  • Duodenum / drug effects*
  • Duodenum / immunology
  • Duodenum / metabolism
  • Dyspepsia / diagnosis
  • Dyspepsia / drug therapy*
  • Dyspepsia / immunology
  • Dyspepsia / metabolism
  • Eosinophilia / diagnosis
  • Eosinophilia / drug therapy*
  • Eosinophilia / immunology
  • Eosinophilia / metabolism
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Pantoprazole / adverse effects
  • Pantoprazole / therapeutic use*
  • Permeability
  • Prospective Studies
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Bile Acids and Salts
  • Inflammation Mediators
  • Proton Pump Inhibitors
  • Pantoprazole

Associated data