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The Ability of Glyphosate to Impair Metabolic Homeostasis Via the Gut Microbiome and Metabolites

Award Number: R01ES033993
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: 09/21/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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The Ability of Glyphosate to Impair Metabolic Homeostasis Via the Gut Microbiome and Metabolites - PROJECT SUMMARY The prevalence of obesity and diabetes continue to rise unabated in the United States, creating a grave social and economic burden. Although development of these diseases is multi-faceted and complex, there is accumulating evidence for the impact of environmental chemical exposures on metabolic homeostasis. Currently, glyphosate is the most commonly used herbicide in the United States, however, to date, no studies have ever assessed whether glyphosate exposure impacts the development of obesity and diabetes. Thus, the long-term goal of this project is to better understand how recent and current pesticide usage can impact long-term metabolic homeostasis. Glyphosate targets the shikimate pathway found in plants, and not mammals, leading to the assumption of its general safety. However, glyphosate can also target bacteria, and glyphosate exposure results in an altered gut microbiome profile. Despite the fact that previous pesticides are associated with metabolic disease, and that glyphosate is known to alter the gut microbiota which can impact energy and glucose homeostasis, no study has ever examined whether exposure to glyphosate can result in development of obesity and/or diabetes. One of the main roles of the gut microbiota is bile acid metabolism, and studies suggest that alterations in bile acid signaling represent a plausible link between the gut microbiota and regulation of metabolic homeostasis via changes in Farnesoid X receptor (FXR) signaling. These facts, coupled with our preliminary data, led to the hypothesis that exposure to glyphosate shifts the gut microbiome, leading to altered intestinal bile acid signaling that contributes to impairments in energy and glucose homeostasis. This hypothesis will be tested in 3 aims: 1) assess if exposure to glyphosate during different developmental timepoints promotes metabolic dysfunction in male and female mice on a chow or high-fat diet, 2) determine the role of the gut microbiome in the effects of glyphosate exposure on metabolic homeostasis, and 3) identify the impact of altered bile acid signaling via glyphosate exposure in impaired metabolic homeostasis. The proposed study will be the first ever to provide mechanistic insight of the effects of glyphosate exposure on metabolic homeostasis. This proposal will provide valuable data leading to further research examining how environmental pesticide usage can affect human health, and possibly identify microbial targets to offset the detrimental effects of environmental chemical use.


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: 2025 ( Subtotal = $385,000 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Environmental Health	001	4	8/4/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$385,000
2025	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Environmental Health	000	3	8/4/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Environmental Health	002	3	8/27/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $385,000

Issue Date FY: 2024 ( Subtotal = $383,750 )
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Environmental Health	000	3	7/16/2024	NON-COMPETING CONTINUATION	$383,750
														Subtotal = $383,750

Issue Date FY: 2023 ( Subtotal = $343,625 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Environmental Health	000	2	7/25/2023	NON-COMPETING CONTINUATION	$343,625
														Subtotal = $343,625

Issue Date FY: 2022 ( Subtotal = $343,625 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Environmental Health	000	1	9/21/2022	NEW	$343,625
														Subtotal = $343,625

Grand Total All Awards = $1,456,000

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The Ability of Glyphosate to Impair Metabolic Homeostasis Via the Gut Microbiome and Metabolites

Award Number: R01ES033993

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: 09/21/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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