Abstract MP45: Proton Pump Inhibitors Increase Pathobiont Species in the Gut Microbiome: Findings from the Baltimore Longitudinal Study of Aging

Background: Proton pump inhibitors (PPIs) have been linked to increased risk of heart and kidney disease, but causal mechanisms remain to be elucidated. Cross-sectional studies have linked PPI use with higher pathobiont bacteria (e.g., Streptococcus ) in the gut microbiome. Here, we aimed to examine the effects of PPIs on the gut microbiome through new-user target-trial emulation. Methods: We included participants from the Baltimore Longitudinal Study of Aging who had ≥2 visits with microbiome data, were ≥60 years old, not on antibiotics, and not on PPIs at baseline. New users were defined as those who initiated PPIs within 2 follow-up visits, while eligible controls reported no PPI use. We matched each new PPI user to 2 non-user controls using a nearest neighbor algorithm and propensity scores based on baseline age, sex, race, ever smoking, history of gastrointestinal conditions (ICD-9 530), obesity, and antidiabetic medication use. We evaluated PPI-related changes in microbial diversity and in the relative abundance (RA) of selected bacteria with ANCOVA and estimated the average treatment effect in the treated using g-computation of marginal effects. Results: After matching each of the 16 new PPI users to 2 non-users, selected from 403 eligible controls, there were no differences in baseline covariates by treatment group. Participants were, on average, 75.5 years old, 60.4% female, and 79.2% white. Mean follow-up was 716.3±251.7 days. By follow-up, PPI initiation non-significantly increased gut microbiome richness by 6.9 species (95% CI: -0.9—14.6) compared to no initiation (Figure). PPI initiation was associated with change in several bacteria in the gut, including the oral pathobionts Streptoccocus parasanguinis and S. salivarius , whose RA were respectively increased by 0.7% (0.02–1.2%) and 3.7% (0.7–6.8%) in the PPI initiators vs controls. Conclusion: PPI initiation increased several pathobiont species in the gut, including Strepcococci spp. commonly found in the oral microbiome and linked to cardiovascular disease.