Effects of Proton Pump Inhibitors on the Gastric Mucosa-Associated Microbiota in Dyspeptic Patients

Abstract

Besides being part of anti-Helicobacter pylori treatment regimens, proton pump inhibitors (PPIs) are increasingly being used to treat dyspepsia. However, little is known about the effects of PPIs on the human gastric microbiota, especially those related to H. pylori infection. The goal of this study was to characterize the stomach microbial communities in patients with dyspepsia and to investigate their relationships with PPI use and H. pylori status. Using 16S rRNA gene pyrosequencing, we analyzed the mucosa-associated microbial populations of 24 patients, of whom 12 were treated with the PPI omeprazole and 9 (5 treated and 4 untreated) were positive for H. pylori infection. The Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria phyla accounted for 98% of all of the sequences, with Helicobacter, Streptococcus, and Prevotella ranking among the 10 most abundant genera. H. pylori infection or PPI treatment did not significantly influence gastric microbial species composition in dyspeptic patients. Principal-coordinate analysis of weighted UniFrac distances in these communities revealed clear but significant separation according to H. pylori status only. However, in PPI-treated patients, Firmicutes, particularly Streptococcaceae, were significantly increased in relative abundance compared to those in untreated patients. Consistently, Streptococcus was also found to significantly increase in relation to PPI treatment, and this increase seemed to occur independently of H. pylori infection. Our results suggest that Streptococcus may be a key indicator of PPI-induced gastric microbial composition changes in dyspeptic patients. Whether the gastric microbiota alteration contributes to dyspepsia needs further investigation. IMPORTANCEAlthough PPIs have become a popular treatment choice, a growing number of dyspeptic patients may be treated unnecessarily. We found that patients treated with omeprazole showed gastric microbial communities that were different from those of untreated patients. These differences regarded the abundances of specific taxa. By understanding the relationships between PPIs and members of the gastric microbiota, it will be possible to envisage new strategies for better managing patients with dyspepsia.

Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract—evidence from next‐generation sequencing studies

“…But similar to the salivary samples, the PPI group exhibited greater phylogenetic diversity of the gastric fluid microbiome, based on unweighted UniFrac distances, while weighted UniFrac distances did not differ significantly . In a cohort of 24 adults undergoing upper gastrointestinal endoscopy for evaluation of dyspepsia, long‐term intake of PPIs in 12 patients was not associated with alterations in species richness or diversity indices, but with increased abundance of the phylum Firmicutes, family Streptococcaceae and genus Streptococcus , independently of H pylori status …”

Systematic review: gastric microbiota in health and disease

“…It should be noted that when detected using conventional methods, H pylori comprises a significant proportion of the ecosystem often representing over 90% of bacteria. Reduced microbial diversity of the gastric microbiota and decreased abundance of other microbial groups is well documented in the case of H pylori colonisation . However, this seems to be a reversible situation.…”

Enlightening discriminative network functional modules behind Principal Component Analysis separation in differential-omic science studies

“…The first question of clinical relevance is whether PPIs exert any effect on the gastric bacterial communities, and this was investigated in a study by Williams and collaborators that was still solely based on culturable gastric bacteria28. More recently, next-generation-sequencing-based metagenomic studies further confirmed that PPIs modify the gastroenteric human microbiota2930313233.…”