Gastric microbiota is altered in oesophagitis and Barrett's oesophagus and further modified by proton pump inhibitors

Abstract

Gastro-oesophageal reflux can cause inflammation, metaplasia, dysplasia and cancer of the oesophagus. Despite the increased use of proton pump inhibitors (PPIs) to treat reflux, the incidence of oesophageal adenocarcinoma has increased rapidly in Europe and in the United States in the last 25 years. The reasons for this increase remain unclear. In this study, we aimed to determine whether the microbiota of the gastric refluxate and oesophageal biopsies differs between patients with heartburn and normal-appearing oesophageal mucosa versus patients with abnormal oesophageal mucosa [oesophagitis or Barrett's oesophagus (BE)] and to elucidate the effect of PPIs on the bacterial communities using 16S rRNA gene pyrosequencing. Significant differences in the composition of gastric fluid bacteria were found between patients with heartburn and normal oesophageal tissue versus patients with oesophagitis or BE, but in the oesophagus-associated microbiota differences were relatively modest. Notably, increased levels of Enterobacteriaceae were observed in the gastric fluid of oesophagitis and BE patients. In addition, treatment with PPIs had dramatic effects on microbial communities both in the gastric fluids and the oesophageal tissue. In conclusion, gastric fluid microbiota is modified in patients with oesophagitis and BE compared with heartburn patients with normal biopsies. Furthermore, PPI treatment markedly alters gastric and oesophageal microbial populations. Determining whether the changes in bacterial composition caused by PPIs are beneficial or harmful will require further investigation.

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

“…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).…”

Recurrent Clostridium difficile infection and the microbiome

“…While Linsky et al found a 42 % increased risk of rCDI with PPI use during incident CDI treatment, a study by Freedberg et al found no such association, instead noting a trend for reduced rCDI with PPI therapy, consistent with reports by Rotramel and colleagues [54,58,59]. Nevertheless, PPIs have been shown to affect the gastric microbiota [60], and a small pilot study recently found that PPI use decreased the diversity of the colonic microbiota [61]; as such, the effects of PPIs on the gut microbiome and rCDI warrant further investigation.…”

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

“…Here, we re-analyzed a dataset by Amir and collaborators29, in order to verify whether the PC-corr method could enhance, in comparison to Amir et al 29,. our understanding of the PPI-induced microbial perturbation.…”

“…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.…”