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

Appl Environ Microbiol. 2016 Oct 27;82(22):6633-6644. doi: 10.1128/AEM.01437-16. Print 2016 Nov 15.


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.

Importance: Although 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.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Bacteroidetes / classification
  • Bacteroidetes / genetics
  • Bacteroidetes / isolation & purification
  • Dyspepsia / drug therapy
  • Dyspepsia / microbiology*
  • Female
  • Firmicutes / classification
  • Firmicutes / genetics
  • Firmicutes / isolation & purification
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / microbiology*
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Genes, rRNA
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / drug effects
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Omeprazole / therapeutic use
  • Proteobacteria / classification
  • Proteobacteria / genetics
  • Proteobacteria / isolation & purification
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*
  • RNA, Ribosomal, 16S / genetics
  • Streptococcus / classification
  • Streptococcus / genetics
  • Streptococcus / isolation & purification


  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • RNA, Ribosomal, 16S
  • Omeprazole