1. Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia.
- Author
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Wauters L, Ceulemans M, Frings D, Lambaerts M, Accarie A, Toth J, Mols R, Augustijns P, De Hertogh G, Van Oudenhove L, Tack J, and Vanuytsel T
- Subjects
- Adult, Belgium, Bile Acids and Salts metabolism, Case-Control Studies, Duodenal Diseases diagnosis, Duodenal Diseases immunology, Duodenal Diseases metabolism, Duodenum immunology, Duodenum metabolism, Dyspepsia diagnosis, Dyspepsia immunology, Dyspepsia metabolism, Eosinophilia diagnosis, Eosinophilia immunology, Eosinophilia metabolism, Female, Humans, Inflammation Mediators metabolism, Inflammatory Bowel Diseases diagnosis, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases metabolism, Intestinal Mucosa immunology, Intestinal Mucosa metabolism, Male, Mast Cells immunology, Mast Cells metabolism, Pantoprazole adverse effects, Permeability, Prospective Studies, Proton Pump Inhibitors adverse effects, Time Factors, Treatment Outcome, Duodenal Diseases drug therapy, Duodenum drug effects, Dyspepsia drug therapy, Eosinophilia drug therapy, Inflammatory Bowel Diseases drug therapy, Intestinal Mucosa drug effects, Mast Cells drug effects, Pantoprazole therapeutic use, Proton Pump Inhibitors therapeutic use
- Abstract
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. ClinicalTrials.gov, Number: NCT03545243., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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