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Arsenic, the Microbiome & Health Outcomes: Mechanisms to Methods of Intervention

Award Number: R01ES033988
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: 12/07/2022
PERIOD OF PERFORMANCE END DATE: 10/31/2027

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Arsenic, the Microbiome & Health Outcomes: Mechanisms to Methods of Intervention - ABSTRACT The gut microbiome is directly impacted by metals exposure and changes in the gut microbiome affect downstream health. An individual’s microbiome also modifies the health effects of toxicants such as arsenic by transforming them into potentially more or less harmful substances. Thus, understanding the impacts of arsenic on the microbiome, and vice versa, is key to achievable prevention and interventions to mitigate the risk of arsenic to human health – a key goal of the NIEHS. Our team’s prior work using the New Hampshire Birth Cohort Study, with ongoing enrollment and a projected size of 3,000 mother-infant dyads, identified an impact of toxic metals on the developing microbiome during the critical window of 0–3 years of age, when microbes are required for immune development. Specifically, our team showed both a sex-specific dysbiosis and a depletion of the immune-training microbe Bacteroides in arsenic-exposed infants/children. Importantly, this work revealed associations between arsenic exposure, changes in the microbiome, and early immune-mediated health outcomes, including respiratory disease. Our team’s recent work indicates a gut-lung link for arsenic-exposed infants depleted for Bacteroides, thus strongly supporting the hypothesis that gut microbiome composition is a key driver of airway health. This project will test the hypothesis that in the sensitive early-life window (0–3 years), when the developing immune system requires interaction with microbes, arsenic affects the developing microbiome, resulting in a paucity of Bacteroides and its secreted metabolites and ultimately associating with increased inflammation and risk of respiratory diseases such as wheeze, upper respiratory tract infection, and pneumonia later in life (out to 12 years of age). AIM 1. Test the hypotheses, using the longitudinal NHBCS and novel bioinformatic tools, that (i) early-life As exposures via food/water are related to sex-specific perturbations in the intestinal microbiome and (ii) the early- life intestinal microbiome modifies or mediates the effects of As exposure on respiratory health outcomes. AIM 2. Test the hypothesis that As enhances secretion of IL-8 from intestinal epithelia due to lack of a key Bacteroides-secreted short chain fatty acid, propionate, ultimately resulting from changes in the epigenome. AIM 3. Test the hypothesis that add-back of Bacteroides can reverse the effect of Bacteroides-depleted stool in a mouse model, thus serving as a proof-of-concept for probiotic interventions.


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 = $387,254 )
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Environmental Health	000	4	1/14/2026	NON-COMPETING CONTINUATION	$387,254
														Subtotal = $387,254

Issue Date FY: 2025 ( Subtotal = $387,254 )
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Environmental Health	000	3	11/26/2024	NON-COMPETING CONTINUATION	$387,254
														Subtotal = $387,254

Issue Date FY: 2024 ( Subtotal = $386,670 )
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Environmental Health	000	2	10/20/2023	NON-COMPETING CONTINUATION	$386,670
														Subtotal = $386,670

Issue Date FY: 2023 ( Subtotal = $401,471 )
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Environmental Health	000	1	12/7/2022	NEW	$401,471
														Subtotal = $401,471

Grand Total All Awards = $1,562,649

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Arsenic, the Microbiome & Health Outcomes: Mechanisms to Methods of Intervention

Award Number: R01ES033988

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: 12/07/2022

PERIOD OF PERFORMANCE END DATE: 10/31/2027

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