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

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

doi:10.3390/ijms222413609

Abstract

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.

Highlights

Functional dyspepsia (FD) is a common functional gastrointestinal (GI) disorder defined by symptoms originating from the gastroduodenal region [1]
Besides differential mucus-associated genera in FD patients vs. controls, we show an association between Streptococcus and duodenal pump inhibitors (PPI) effects in controls, suggesting a role for duodenal dysbiosis after long-term PPI therapy in FD
PPI therapy was started in 30 controls and 28 FD-starters and withdrawn in 19 FD-stoppers after exclusion of Helicobacter pylori (Figure 1)

Summary

Introduction

Functional dyspepsia (FD) is a common functional gastrointestinal (GI) disorder defined by symptoms originating from the gastroduodenal region [1]. Increasing data point toward duodenal alterations in FD pathophysiology, including mucosal hyperpermeability and low-grade inflammation [2]. The causes are unknown but candidates include luminal acid, bile salts and microbiota [2,3]. Gut commensals play an essential role in nutrient acquisition, colonization resistance, epithelial barrier function and immune development [4,5]. Disruption of the gut ecosystem or dysbiosis has been described in different GI disorders based on stool samples, which do not accurately reflect the mucosal microbiome [6]. Evidence for dysbiosis is mounting in irritable bowel syndrome (IBS) but is scarce for FD, despite the latter being even more prevalent than IBS [7]

Objectives

Methods

Results

Discussion

Conclusion