Untargeted Metabolomics Profiling of a PFAS-Exposed Flemish Population.

Area of Science:

• Environmental Health
• Metabolomics
• Toxicology

Background:

• Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants with widespread human exposure.
• Concerns exist regarding the long-term metabolic health effects of PFAS accumulation.
• This study investigates PFAS-associated metabolic alterations in a population near a production facility.

Purpose of the Study:

• To characterize serum metabolic and lipidomic alterations in a Flemish population exposed to PFAS.
• To identify specific metabolites and metabolic pathways affected by high PFAS exposure.
• To explore a potential metabolic signature for PFAS exposure.

Main Methods:

• Untargeted metabolomics and lipidomics on serum samples from 82 adults.
• Stratification into high-exposure (median 162.0 ng/mL PFAS) and low-exposure (median 7.2 ng/mL PFAS) groups.
• Analysis using four LC-HRMS platforms and statistical comparisons.

Main Results:

• 38 metabolites were significantly altered between exposure groups.
• High PFAS exposure showed increased phosphatidylglycerols (PG), phosphatidylinositols, phosphatidylethanolamines (PE), and triacylglycerols (TG), and decreased sphingomyelins.
• Perturbations in glycerophospholipid and sphingolipid metabolism were observed; a five-metabolite panel demonstrated moderate discrimination (AUC=0.753).

Conclusions:

• PFAS exposure is associated with coordinated changes in serum lipid metabolism.
• A small panel of five metabolites may serve as a complementary biomarker for PFAS biological effects.
• Further research can utilize these findings to understand PFAS-related metabolic disruption.