Anti-Acid Drug Treatment Induces Changes in the Gut Microbiome Composition of Hemodialysis Patients

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.

Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease

“… 61 Many drugs have documented impact on gut microbiota composition. 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 For example, phosphate binders can affect gut microbiota by impairing vitamin and phosphate absorption. 62 Besides affecting microbiota, calcium‐based phosphate binders may further increase the risk of extra‐skeletal calcifications by inducing a rise in serum calcium levels or reducing intestinal absorption of vitamin K2.…”

“…Chronic kidney disease and its frequent comorbidities leads to polypharmacy (defined as the continuous use of five or more medications per day) in 80% of patients, of whom 20% use >10 different medications per day 61 . Many drugs have documented impact on gut microbiota composition 62‐69 . For example, phosphate binders can affect gut microbiota by impairing vitamin and phosphate absorption 62 .…”

“…The frequent use of antibiotics by CKD patients does not only impact the target pathogen but also commensal gut bacteria 63 . Proton‐pump inhibitors (PPI), another class of medications commonly used by CKD patients, have been associated with important changes in gut microbiome because of long‐term reduction of gastric acid secretion and hypochlorhydria 65‐67 . Finally, immunosuppression therapy after kidney transplantation can induce profound alterations in gut microbiota composition 65,68 …”

“…63 Proton-pump inhibitors (PPI), another class of medications commonly used by CKD patients, have been associated with important changes in gut microbiome because of long-term reduction of gastric acid secretion and hypochlorhydria. [65][66][67] Finally, immunosuppression therapy after kidney transplantation can induce profound alterations in gut microbiota composition. 65,68 Interestingly, deregulations in gut microbiota may contribute to vascular and bone disease in CKD patients (the 'gut-vascular-bone axis'), among others through a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, an altered intestinal barrier function and impaired vitamin K status.…”

Gastric acid suppressants and cognitive decline in people with or without cognitive impairment

“… 27 Anticholinergic burden may explain the association between H2RA use and cognitive decline particularly among those with loss of cholinergic synapses in MCI and AD. Also, PPIs and H2RAs were suggested to have differential effects on gut microbiome, 46 which might be explored as a mediator. As a limitation, data on the microbiome and H. pylori infection were not available in the dataset precluding subgroup analyses for different indications.…”