Impact of Proton-Pump Inhibitor Use on Gut Microbiota Composition and Other Markers of Health in Older Adults

Abstract

The composition and diversity of the gut microbiota interact with the host immune system to prevent infection and limit accumulation of pathogen-related toxins. Proton-pump inhibitors (PPIs) may affect the gut microbiota by directly targeting bacterial proton pumps and/or affecting the microenvironment of the flora; however, the extent to which PPIs alter gut microbiota composition and other markers of health is unknown. This was a prospective study of healthy volunteers from San Antonio, TX from June to November 2016. Included subjects were ≥60 years old and had no recent use of medications known to affect the gut microbiota. Participants provided a blood and stool sample at baseline, completed a 14-day course of omeprazole 20mg daily, then provided a follow-up blood and stool sample. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via Mothur’s Bayesian classifier and referenced to the Greengenes database. OTU richness and Shannon diversity were compared between samples using the Wilcoxon signed rank test. Abundance-weighted sample differences were calculated using the Bray-Curtis dissimilarity. PERMANOVA was used to assess the impact of PPI use on β diversity. Systemic inflammatory markers (interleukin [IL]-6, IL-10, and tumor necrosis factor [TNF]-alpha) and insulin-like growth factor (IGF-1) were analyzed using ELISA and compared using the paired t-test. A total of 24 subjects completed the study (mean age 71 years; 63% female). OTU richness (P = 0.32) and Shannon diversity (P = 0.28) were similar between pre- and post-PPI samples. PPI use was associated with significantly lower abundance of Actinobacteria, Lachnospiraceae, Erysipelotrichaceae, and Bifidobacteriaceae. Β diversity was significantly associated with PPI use (P < 0.0001). PPI use was associated with a significant increase in mean IL-10 (5.7 vs. 4.7, P = 0.0385) and decrease in mean IGF-1 (87.5 vs. 94.8, P = 0.0185), while TNF-alpha (1.4 vs. 1.4, P = 0.9180) and IL-6 (4.6 vs. 3.4, P = 0.0808) were statistically similar between groups. Short-term, over-the-counter PPI use was associated with significant changes in gut microbiota composition and other markers of health in older adults. All authors: No reported disclosures.