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

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.

Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients

“…In addition, PPIs have been used as short-term drugs to improve the gastrointestinal symptoms of SLE. However, some studies have found that the long-term use of PPIs could have adverse effects [ 24 , 25 ]. Future research might hence benefit from longer trials where PPI treated SLE patients are followed for longer periods of time collecting samples at various points in time.…”

Immune Activation in Functional Dyspepsia: Bystander Becoming the Suspect

“…Increased presence of luminal Streptococcus was reported in FD compared to controls and correlated to upper GI symptoms in both PDS and EPS subgroups ( Fukui et al, 2020 ). We recently provided evidence for the involvement of luminal Porphyromonas in FD, with an inverse association of the genus abundance to GI symptoms and duodenal eosinophilia, suggesting a link with immune activation ( Wauters et al, 2021g ). In addition, the efficacy of a combination of two spore-forming probiotic Bacillus strains was demonstrated in a placebo-controlled study in FD, with decreased peripheral Th17 signaling and increased Faecalibacterium and Roseburia in stools, suggesting immunomodulatory properties of probiotic therapy in FD ( Wauters et al, 2021f ).…”

Role of the duodenal microbiota in functional dyspepsia

“…Dyspeptic patients also demonstrated increased anaerobic metabolism in the gastric microbial community in conjunction with increased Pseudoclavibacter and Tannerella , increased Veillonella, Cohnella, Sporolactobacillus, Propionigenium in saliva, and a higher duodenal prevalence of Rothia , Clostridium, Haemophilus , and Actinobacillus species 90 . A recent study demonstrated decreased duodenal mucosal Neisseria and Porphyromonas abundance in FD patients and controls prior to treatment with PPIs, but no differences in microbial load 91 . These findings are presented in Table 1.…”