Abstract Body: 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.