Abstract
Anti-acid drugs, proton pump inhibitor (PPI) and histamine-2 blocker (H2-blocker), are commonly prescribed to treat gastrointestinal disorders. These anti-acid drugs alter gut microbiota in the general population, but their effects are not known in hemodialysis patients. Hence, we investigated the microbiota composition in hemodialysis patients treated with PPIs or H2-blocker. Among 193 hemodialysis patients, we identified 32 H2-blocker users, 23 PPI users, and 138 no anti-acid drug subjects. Fecal samples were obtained to analyze the gut microbiome using 16S RNA amplicon sequencing. Differences in the microbial composition of the H2-blocker users, PPI users, and controls were assessed using linear discriminant analysis effect size and the random forest algorithm. The species richness or evenness (α-diversity) was similar among the three groups, whereas the inter-individual diversity (β-diversity) was different between H2-blocker users, PPI users, and controls. Hemodialysis patients treated with H2-blocker and PPIs had a higher microbial dysbiosis index than the controls, with a significant increase in the genera Provetella 2, Phascolarctobacterium, Christensenellaceae R-7 group, and Eubacterium oxidoreducens group in H2-blocker users, and Streptococcus and Veillonella in PPI users. In addition, compared to the H2-blocker users, there was a significant enrichment of the genera Streptococcus in PPI users, as confirmed by the random forest analysis and the confounder-adjusted regression model. In conclusion, PPIs significantly changed the gut microbiota composition in hemodialysis patients compared to H2-blocker users or controls. Importantly, the Streptococcus genus was significantly increased in PPI treatment. These findings caution against the overuse of PPIs.
Highlights
The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host
The H2 -blocker users were more likely to be male than pump inhibitor (PPI) users or controls, with the control group having a higher blood phosphate level and single pool Kt/V than H2 -blocker users or PPI users
Regarding the random forest model predicted specific taxa, there was increased S. salivarius species, genus Streptococcus, and family Streptococcaceae in PPI users compared to H2 -blocker users or controls
Summary
The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Long-term anti-acid drugs have been found to be associated with several adverse events, such as osteoporosis, fracture, hypomagnesemia, vitamin B12 deficiency, iron deficiency anemia, CKD, dementia, and pneumonia [5,6]. PPIs have been associated with an increased risk of mortality [7], major adverse cardiovascular events [8], vascular calcification [9], and hip fracture [3] in patients with kidney disease. The long-term reduction of gastric acid secretion by PPIs was suggested to decrease gut microbial richness, alter the composition of both gastric and intestinal microbiota, and increase oral bacteria and potentially pathogenic bacteria [10,11]. Studies have suggested profound changes in PPI users’ gut microbiota in the general population, this has not been investigated in ESRD patients. Our study aimed to evaluate the influence of two antiacid drugs (H2 -blocker and PPI) on the fecal microbiome in hemodialysis patients
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