Per- and polyfluoroalkyl substances (PFAS) are persistent environmental chemicals widely detected in human populations and are associated with multiple adverse health outcomes, including metabolic disorders, liver dysfunction, cardiovascular disease, and immune dysregulation. Due to their strong protein binding and resistance to degradation, effective strategies to reduce internal PFAS burden in humans remain limited.
Emerging evidence suggests that the gut microbiota may play a critical role in xenobiotic metabolism and elimination, particularly through modulation of bile acid metabolism and enterohepatic circulation. However, population-based evidence linking gut microbiota composition, hepatic-intestinal cycling, and PFAS excretion in humans is currently lacking.
This project aims to investigate whether variation in gut microbiota-related traits is associated with differences in PFAS elimination and circulating PFAS levels, and whether modulation of the gut-liver axis may represent a potential pathway to reduce PFAS-related disease risk.
The primary research questions are:
Are gut microbiota-associated metabolic traits linked to circulating PFAS concentrations in the general population?
Do markers of enterohepatic circulation and liver function mediate the relationship between gut microbiota-related factors and PFAS burden?
Is reduced PFAS burden associated with lower risk of PFAS-related adverse health outcomes?
Using UK Biobank data, this study will integrate biomarker data, liver-related phenotypes, dietary and metabolic indicators, and health outcomes to explore population-level associations and potential mediating pathways. The scientific rationale is to identify modifiable biological mechanisms involved in PFAS elimination, providing an evidence base for future microbiota-targeted or dietary interventions aimed at reducing PFAS exposure and its health consequences.
