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.

Autor: Hampson HE; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Li S; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Walker DI; Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Wang H; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Jia Q; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Rock S; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Costello E; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Bjornstad P; UW Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA, USA; Section of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA., Pyle L; Section of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA., Nelson J; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Gilliland FD; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Chen Z; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Aung M; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Chatzi L; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Conti DV; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Alderete TL; Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Goodrich JA; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: jagoodri@usc.edu.
Jazyk: angličtina
Zdroj: The Science of the total environment [Sci Total Environ] 2024 Dec 01; Vol. 954, pp. 176519. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1016/j.scitotenv.2024.176519
Abstrakt: 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) is associated with increased risk of CKD, yet studies examining the mechanisms linking PFAS and kidney function are lacking. In this exploratory study, we examined longitudinal associations of PFAS exposure with kidney function, and tested 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 mediation analyses with the microbiome and circulating metabolites, a joint component (characterized by reduced Lachnospiraceae and 17b-estradiol and increased succinate, retinoate and dodecanoic acid) and a metabolite component (characterized by increased hypotaurine and decreased D-pinitol and ureidopropionate) mediated 38 % and 50 % of the effect between PFAS burden score and eGFR, respectively.
Conclusion: Our proof-of-concept analysis provides the first evidence that reduced short-chain fatty acid-producing bacteria and anti-inflammatory metabolites may link PFAS exposure with impaired kidney function. This study raises the possibility of future targeted interventions that can alter gut microbiome or circulating metabolite profiles to prevent PFAS induced kidney damage.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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