Influence of Proton-Pump Inhibitors on the Luminal Microbiota in the Gastrointestinal Tract

Abstract

Objectives:The objective of this study was to investigate comparatively the influence of proton-pump inhibitors (PPI) administration on three bacterial communities in the oral cavity, stomach, and colon along the alimentary tract.Methods:Forty-five subjects including 18 patients taking PPI were enrolled. Stimulated saliva, gastric fluid (GF), and feces were obtained from each subject for the microbiota analysis through bacterial 16S rRNA gene profiling using the pyrosequencing method.Results:The species richness (alpha diversity) was similar among these three microbiota, whereas the interindividual diversity (beta diversity) was much higher in the fecal microbiota compared with that in the others. The UniFrac analysis indicated that the salivary and GF microbiota were similar to one another; however, both differed greatly from the fecal microbiota in the overall bacterial community structure. In the comparison between PPI-users and PPI-nonusers, a bacterial cell number increase of ~1,000 times was found in the GF of PPI-users using culturing methods, whereas the bacterial number and composition were nearly identical between the two groups using quantitative PCR and a similarity search based on 16S profiling. The beta diversity significantly increased in both the salivary and GF microbiota of PPI-users compared with PPI-nonusers.Conclusions:These results suggest that the GF microbiota has recently moved from the saliva. Bacterial overgrowth in the GF by PPI administration may be due to a lack of killing rather than proliferation of the bacteria in the acid-suppressed stomach. The biological significance of the increase in beta diversity by PPI administration remains unclear.

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

“…In the pioneer studies by Bik et al (39) and Li et al (41) on the gastric mucosa-associated microbiota, Streptococcus and Prevotella were detected as the two major abundant genera, although these studies analyzed two geographically and ethnically divergent populations and two medically different populations. Surprisingly, Streptococcus and Prevotella were also detected as the top two genera in the gastric luminal microbiota, suggesting similarities of the bacterial compositions between the two intragastric compartments (11). Thus, the question of whether specific, stomach-resident microbial communities or bacterial groups/organisms may contribute to or be associated with, the development of gastric disease becomes intriguing (43,45,46).…”

“…Indeed, whatever the mechanisms by which PPIs affect microbes (9), gastric acid suppression proved to substantially increase the number of cultivable non-H. pylori bacteria in either the gastric mucosa or the stomach lumen; notably, this effect was largely influenced by the infection with H. pylori and the duration of acid suppression, which occurred through both histamine 2 -receptor antagonists (H 2 RA) and PPIs (10). By means of nonculturing methods (i.e., quantitative PCR and 16S rRNA gene pyrosequencing), a recent study by Tsuda et al revealed very similar bacterial numbers in the gastric fluid mi-crobiota between PPI users and PPI nonusers (11). However, the PPI administration induced a small but significant increase in the intersubject diversity (11), which was consistent with previous findings by Amir et al showing an increase in the beta diversity of the gastric fluid microbiota of subjects after 8 weeks of PPI treatment (12).…”

“…By means of nonculturing methods (i.e., quantitative PCR and 16S rRNA gene pyrosequencing), a recent study by Tsuda et al revealed very similar bacterial numbers in the gastric fluid mi-crobiota between PPI users and PPI nonusers (11). However, the PPI administration induced a small but significant increase in the intersubject diversity (11), which was consistent with previous findings by Amir et al showing an increase in the beta diversity of the gastric fluid microbiota of subjects after 8 weeks of PPI treatment (12). Furthermore, H. pylori was found to be a minor bacterium in the gastric luminal samples in the Tsuda and coworkers' study (11), whereas, as expected, the organism was identified as a dominant bacterium in gastric mucosal samples from H. pyloriinfected patients (13).…”

Proton Pump Inhibitors in Veterinary Medicine

“…There are several studies regarding PPI induced alterations of the microbiome throughout the gastrointestinal tract (from oral cavity to colon) and its potential results in humans (Freedberg et al, 2014;Tsuda et al, 2015). However, the true cause-effect relationship between PPIs and gastrointestinal bacterial overgrowth has not been established in animals (Kaya 2007;Papich, 2009;Wallacei and Sharkey, 2011;Garcia-Mazcorro et al, 2012) reported that orally administered omeprazole can change the quantitation of various bacteria groups in the gastrointestinal tract of healthy dogs (a decrease in Helicobacter spp.…”

Are Blastocystis species clinically relevant to humans?

“…Sex hormone modulation of the gut microbiota has been reported (Mulak et al 2014) and it is likely OCP therapy has some impact on the FM. Approximately one third of subjects with IBS were taking acid suppression therapy that has been reported to change the gastric microbiome significantly but have much less effect on the FM (Tsuda et al 2015).…”