The Potential Mediating Role of the Gut Microbiome and Metabolites in the Association Between PFAS and Kidney Function in Young Adults: A proof-of-concept study
Abstract
Background: Chronic kidney disease (CKD) affects over 10% of the global population and can lead to kidney failure and death. Exposure to per- and polyfluoroalkyl substances (PFAS) are associated with increased risk of CKD, yet studies examining the potential mechanisms linking PFAS and kidney function are lacking. We aimed to examine longitudinal associations of PFAS exposure with kidney function, and test if associations were mediated by altered gut bacterial taxa or plasma metabolites using a multi-omics mediation analysis. Methods: Seventy-eight young adults from the Children’s Health Study were included in this longitudinal cohort study. At baseline, seven plasma PFAS and untargeted plasma metabolomics were measured using liquid chromatography/mass-spectrometry. Baseline gut bacterial abundance was characterized using 16S rRNA sequencing and examined at the genus level. At follow-up, serum creatinine and cystatin C concentrations were quantified to estimate glomerular filtration rate (eGFR). High-dimensional multi-omics analyses were conducted to assess the association between baseline PFAS exposure with follow-up eGFR, mediated by gut microbiome and circulating metabolite levels. Results: PFAS burden score, a variable developed to estimate exposure to chemical mixtures, was associated with kidney function. Each standard deviation increase in baseline PFAS burden score was associated with a 2.4% lower eGFR at follow-up (95% CI:[0.1%,4.8%]). Following high-dimensional…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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