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

Award Number: R01ES038206
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/04/2026
PERIOD OF PERFORMANCE END DATE: 04/03/2030

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $2,864,424 )
2026	2026	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Environmental Health	000	1	4/2/2026	NEW	$2,864,424
														Subtotal = $2,864,424

Grand Total All Awards = $2,864,424

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

Award Number: R01ES038206

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/04/2026

PERIOD OF PERFORMANCE END DATE: 04/03/2030

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