Environmental PFAS alter microbial function, impair host metabolism, and drive disease progression

About This Grant

ABSTRACT Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants known for their widespread use and adverse effects on human health (e.g., metabolic disease, cancer). Early-life exposure to PFAS is of particular concern as developmental periods are a critical window of vulnerability during which disruptions to the gut microbiota and host metabolism can have long-lasting consequences. Infants and young children are exposed to PFAS through breast milk, formula, and contaminated food or water. Despite the recognition that many environmental pollutants influence the gut microbiota, there is a lack of research assessing PFAS-induced microbiome toxicity using quantifiable and biologically meaningful endpoints. Further, given the essential connection between the host and microbiome, there is a critical need to study the impact of PFAS on the physiology and function of gut microbes and the resulting effects on host health. The proposed studies will address these gaps by elucidating the mechanisms by which PFAS influences host-microbiome interactions. The central hypothesis of this grant is that gut microbes modify PFAS toxicokinetics and mediate PFAS- associated health outcomes via the disruption of host-microbe homeostasis. Herein we present a paradigm- shifting view of bacterial-mediated mechanisms of PFAS toxicity. Two specific aims will test this hypothesis: Specific Aim 1 will evaluate the effects of PFAS on diverse gut microbes to understand microbial toxicity, bioaccumulation, and adaptation in microbial species key to health. For Specific Aim 2, mouse models will be used to determine how early-life PFAS exposure disrupts the host-gut microbiome axis leading to metabolic disorders in adulthood. Our interdisciplinary team combines expertise in perfluorinated chemical toxicology, microbiology, metabolomics, and biostatistics. To comprehensively study how PFAS exposure is linked to detrimental health outcomes, our studies use state-of-the-art technologies (e.g., metagenomics, metabolomics) to explore microbial toxicity and the broader effects of environmental chemicals on gut microbiome and its community structure and function. Results from the proposed studies will provide new and impactful data that will provide for more personalized risk assessment frameworks and support the development of microbiome- centered therapeutic strategies to mitigate the health impacts of PFAS.