PFAS May Affect Kidneys via Gut Microbes, Blood Metabolites

TOPLINE:

Greater exposure to per- and polyfluoroalkyl substances (PFAS) is linked to reduced kidney function in young adults, mediated by changes in the gut microbiome and metabolites, including reduced anti-inflammatory bacteria and metabolites.

METHODOLOGY:

• Exposure to PFAS is associated with an increased risk for chronic kidney disease, yet studies examining the mechanisms linking PFAS to kidney function are lacking.
• This exploratory study aimed to examine the association of PFAS exposure with kidney function and test if these associations were mediated by altered gut microbiome or plasma metabolites in 78 young adults (mean age, 20 years; 53% women; 56% Hispanic) with overweight or obesity in early adolescence, who were at high risk for metabolic disease.
• Blood samples were collected at baseline and at 4-year follow-up. Baseline levels of seven PFAS and 367 plasma metabolites were measured and selected for analysis. A PFAS burden score was calculated to assess the cumulative exposure.
• The primary outcome was the estimated glomerular filtration rate (eGFR) at follow-up, calculated using serum creatinine and cystatin C measurements from the 4-year follow-up.
• The relative abundance of gut microbiota taxa was quantified from participant stool samples at baseline. Omics features were selected for high-dimensional mediation analysis, both by a p-value threshold of 0.05 and by having different directions of association, such as positively linked to a PFAS and negatively linked with eGFR.

TAKEAWAY:

• Each SD increase in the baseline PFAS burden score was associated with a 2.4% lower eGFR at follow-up (95% CI, −4.8% to −0.1%).
• A protective component with five joint gut microbiome and metabolite factors mediated 38% of the effect between the PFAS burden score and eGFR, when adjusted for confounders.
• A protective component of five individual metabolite factors mediated 50% of the effect between the PFAS burden score and eGFR, after adjustment for covariates.
• The study suggests reduced short-chain fatty acid–producing bacteria and anti-inflammatory metabolites, as well as increases in inflammatory metabolites, may link PFAS exposure with impaired kidney function.

IN PRACTICE:

“Together, these results provide evidence suggesting that the associations of PFAS exposure on kidney function may be mediated by alterations in gut microbial taxa and metabolic profiles in young adults,” the authors wrote. “Therefore, the interplay between the gut microbiome and metabolites may be contributing to the mediating effects of PFAS exposure on decreased kidney function.”

SOURCE:

The study was led by Hailey E. Hampson, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles. It was published online in Science of the Total Environment.

LIMITATIONS:

The study’s sample size was relatively small and consisted of young adults with overweight or obesity, which may affect the generalizability of the findings. The gut microbiome data of some participants were missing, requiring imputation, which could have introduced bias. Additionally, data on the exposure (PFAS) and mediators (gut microbiome and metabolites) were collected at the same timepoint, which may have affected the causal interpretation of the results. The assessment of eGFR as an indicator of kidney function has some limitations. More studies are needed to validate results in larger samples and other populations, to examine the mechanisms of action, and to determine if modifying the gut microbiome may alter PFAS-induced kidney damage.

DISCLOSURES:

This study was supported by the National Institute of Environmental Health Science. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.