(P27-017-24) Gut Microbial Pathways Associated With Proton Pump Inhibitor Use in Boston-Area Puerto Rican Adults

Objectives: Proton pump inhibitors (PPIs) are used to treat gastrointestinal (GI) disorders, and are one of the most highly utilized medications worldwide; however, there are several side effects attributed to use. Change in gastric acidity by PPIs is associated with gut microbial changes. Previous work shows high PPI use in the Boston-Puerto Rican Health Study (BPRHS) participants. In addition, enrichment of stool-derived Streptoccous anginosus, S. salivarius and S. parasanguinis  among PPI users was observed. Building on these findings, we sought to further examine microbial pathways associated with PPI use.

Methods: The BPRHS is a longitudinal cohort that enrolled Puerto Rican adults at baseline (1499) through wave 4 (~12.7y). Our analysis included 309 participants with self-collected stool samples that underwent metagenomic profiling. PPl use was self-reported and classified as any use (yes/no) in the past 30d. Cross-sectional associations between gut microbial pathways and PPI use were examined including 1) differentially abundant microbial pathways using Microbiome Multivariable Associations with Linear Models (MaAsLin2), 2) discriminative classification using random forest (RF), and 3) correlation between gut microbial taxa and pathways enriched with PPI use.

Results: Among 309 participants (68.8y ± 7.3y; female 74.6%), 112 (36.2%) self-reported PPI use. After adjusting for relevant covariates, we observed an enrichment of several pathways including fructan (β= 2.01, FDR P = 0.01), and butanediol (β= 1.81, FDR P = 0.02) biosynthesis among PPI users. Pathway-based RF classifier discriminated PPI users with mean ROC 0.67 (± 0.07). S. salivarius and S.parasanguinis were correlated with fructan biosynthesis (rho= 0.97 and 0.76, respectively) and butanediol biosynthesis (rho= 0.78, and 0.75, respectively).

Conclusions: Among PPI users, there was an observed enrichment of gut microbial pathways, including fructan biosynthesis, correlated with S. salivarius and S. parasanguinis, suggesting changes in microbial pathways associated with prebiotic fiber hydrolysis in response to gastric pH changes. Further, it is reported that Streptococci may synthesize butanediol and 2,3-butanedione which may harm host tissue by immune mediated and other synergistic mechanisms, thus impacting health.

Funding Sources: NIH P50HL105185 P01AG023394 R01AG055948