Abstract
The association between adverse effects of PPI and gut microbiota in old age has yet to be elucidated. We assessed changes in the gut microbiota and butyrate levels following the long-term administration of PPIs to old rats and investigated their associations. F344 aged male rats were fed a PPI-supplemented diet for 50 weeks. The ileal microbiota was analysed by metagenomic sequencing of the 16S rRNA, while the butyrate concentration was measured by high-performance liquid chromatography. We observed a significant decrease in microbial diversity following PPI administration in the 2-year-old rats but not in the 74-week-old rats. PPI treatment reduced both commensal bacteria and opportunistic pathogens, particularly in the 2-year-old rats. Enterotypes comprising the majority of the control samples were enriched in Lactobacillus, while other enterotypes in the PPI group were dominated by Turicibacter or Romboutsia. The PPI treatment reduced the butyrate concentrations in the intestines and colons of 74-week-old rats compared to the control group. The abundance of Lactobacillus significantly correlated with butyrate concentrations in 74-week-old rats. In conclusion, long-term administration of PPIs alters the gut microbiota and butyrate concentrations in rats, particularly in old age, which may be an underlying mechanism of PPI-induced adverse effects such as pseudomembranous colitis.
Highlights
Proton pump inhibitors (PPIs) induce gastric acid suppression and are commonly prescribed medications in the treatment of gastrointestinal disorders
We investigated the effect of long-term PPI administration on gut microbiota of 74-week-old Fischer 344 (F344) rats, and confirmed that the long-term administration of PPIs induced alterations in the microbiota of the terminal ileum of F344 rats[10]
Luminal bacteria tend to affect the host through the production of metabolites, such as short-chain fatty acids (SCFAs) and gases, whereas adherent bacteria are more associated with mucosal immunity
Summary
Proton pump inhibitors (PPIs) induce gastric acid suppression and are commonly prescribed medications in the treatment of gastrointestinal disorders. A significant reduction in gut microbial diversity was observed after long-term PPI administration[5], while no significant changes were observed in other studies involving short- or long-term PPI administrations[3,6] Due to these varying results, the ability of PPIs to potentially induce alterations in gut microbiota must be demonstrated with additional evidence. We investigated the effect of long-term PPI administration on gut microbiota of 74-week-old Fischer 344 (F344) rats (approximately 60 years in humans), and confirmed that the long-term administration of PPIs induced alterations in the microbiota of the terminal ileum of F344 rats[10] In addition to these findings, the results of the present study further demonstrate the association between ageing and PPI-induced microbial changes by studying rats at a frailer age (104-week-old, equal to 2-year-old rats, approximately 80 years in humans) and by estimating changes in the concentrations of microbial products. The present study investigated the level of butyrate in four intestinal regions, the duodenum, jejunum, ascending and descending colon, making this the first study to measure the PPI-induced changes in butyrate concentration in diverse regions of the small and large intestines
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