The influence of long-term use of proton pump inhibitors on the gut microbiota: an age-sex-matched case-control study

Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux and prevent gastric ulcers, and have been considered as low risk. However, recent studies have identified possible associations between PPI use and gut microbiota, suggesting that PPIs use increases the risk of enteric infections, including <i>Clostridium difficile</i> infection. To investigate gut microbiota in Japanese PPIs users, we conducted 16S metagenomics analysis of fecal samples collected from PPI users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control subjects) matched by age and sex were recruited and fecal samples were obtained to analyze the gut microbiome using 16S rRNA gene sequencing. There were significant differences in the microbial structure between PPI non-users and PPI users. In contrast, the analysis of α-diversity revealed no significant differences between PPI non-users and PPI users. When comparing in genus level between these two groups, the genera <i>Streptococcus</i> was significantly abundant and the genera <i>Faecalibacterium</i> was significantly decreased in PPI users. Our findings indicate a probable association between PPI use and the alternation of microbiota. These alterations might provide a mechanism by which PPIs predispose enteric infection such as <i>Clostridium difficile</i> infection.