☆ 4.8 Article

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

GASTROENTEROLOGY (2021)

Journal

GASTROENTEROLOGY

Volume 160, Issue 5, Pages 1521-+

Publisher

W B SAUNDERS CO-ELSEVIER INC

DOI: 10.1053/j.gastro.2020.12.016

Keywords

Functional Dyspepsia; Proton Pump Inhibitor; Inflammation; Permeability

Funding

Flanders Research Foundation (FWO Vlaanderen)
Methusalem grant of Katholieke Universiteit Leuven
clinical research fund (KOOR) of the University Hospitals Leuven

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Abstract

This study found that the numbers of eosinophils and immune cells in the duodenum, as well as permeability, were significantly higher in patients with functional dyspepsia, and decreased after PPI therapy. In contrast, immune cells and permeability increased in healthy volunteers on PPIs.

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 Gastro intestinal 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.

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Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia

Lucas Wauters, Raul Y. Tito, Matthias Ceulemans, Maarten Lambaerts, Alison Accarie, Leen Rymenans, Chloe Verspecht, Joran Toth, Raf Mols, Patrick Augustijns, Jan Tack, Tim Vanuytsel, Jeroen Raes

Summary: The study found differential mucus-associated genera between FD patients and controls, with Streptococcus positively correlating with duodenal eosinophils in controls. While short-term PPI therapy effects were unrelated to changes in the gut microbiota for FD patients, increased Streptococcus in controls was associated with duodenal PPI effects, even after long-term therapy withdrawal in FD stoppers.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)