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Role of the gut microbiome in pesticide-induced effects on child neurodevelopment

Award Number: R01ES031322
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: 02/17/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Role of the gut microbiome in pesticide-induced effects on child neurodevelopment - SUMMARY Pesticides are pervasive in our environment, and have accumulated in drinking water reserves serving millions of people worldwide, causing growing concern since the potential adverse health effects are not fully understood. In 2017 alone, the world used about 6.8 million tons of pesticides, of which the world's largest usage is in China and the United States. More recently it has been discovered that pesticides have strong effects on microbial communities, extinguishing entire clades while promoting growth in others. Shifts in microbial composition have been associated with brain development, mood and behavior suggesting a strong link between the gut and the brain. We hypothesize that there may exist an unappreciated microbiome component to the adverse health effects of pesticide exposure. In this proposal, we will use a comprehensive approach to identify the microbial components of pesticide susceptibility to neurodevelopmental delay. Specifically, in Aim 1 we will investigate the impact of prenatal exposure to 11 targeted pesticides on child neurodevelopment in a large well-defined human Mother and Child Microbiome Cohort (MCMC) consisting of 3000 mother and child pairs. Study participants are currently followed up regularly until the children reach 4 years of age. Comprehensive artificial intelligence analysis of pesticide exposure and children's early neurodevelopment data will identify key pesticides that negatively impact child development. In Aim 2, we hypothesize that prenatal exposure to pesticides can shift the composition of the GM and subsequently lead to abnormal neurodevelopment. We will integrate the child gut microbiome data with maternal pesticide exposure during pregnancy and child neurodevelopment data to investigate the impact of prenatal exposure to targeted pesticides on child gut microbiome and development. This Aim will identify specific gut bacteria or clades associated with child neurodevelopment. In Aim 3, we will use conventional and germ-free mouse models to elucidate mechanisms by which pesticide exposure can affect the gut microbiome and behavior. Conventionally housed pregnant mice will be exposed to pesticides and the gut microbiome and behavior (anxiety, memory, motor performance, social interaction) will be analyzed in their offspring. Also, germ-free mice will be colonized with specific bacteria or bacterial clades to study the causality of the impact of the GM on behavior. The long-term implications for human health are significant – it may be possible to increase tolerance/robustness to pesticide exposure by providing sensitive individuals with probiotics that have select degradation pathways. Moreover, this understanding is important in order to formulate novel preventive strategies including educating health practitioners, families, and public health providers and organizations regarding the potential risks of environmental exposures.


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: 2024 ( Subtotal = $283,200 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Environmental Health	000	5	3/11/2024	NON-COMPETING CONTINUATION	$283,200
2024	2024	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Environmental Health	001	5	8/14/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $283,200

Issue Date FY: 2023 ( Subtotal = $283,200 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Environmental Health	000	4	3/20/2023	NON-COMPETING CONTINUATION	$283,200
														Subtotal = $283,200

Issue Date FY: 2022 ( Subtotal = $283,200 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Environmental Health	000	3	12/13/2021	NON-COMPETING CONTINUATION	$283,200
														Subtotal = $283,200

Issue Date FY: 2021 ( Subtotal = $281,700 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Environmental Health	000	2	1/6/2021	NON-COMPETING CONTINUATION	$281,700
														Subtotal = $281,700

Issue Date FY: 2020 ( Subtotal = $282,150 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Environmental Health	000	1	2/17/2020	NEW	$282,150
														Subtotal = $282,150

Grand Total All Awards = $1,413,450

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Role of the gut microbiome in pesticide-induced effects on child neurodevelopment

Award Number: R01ES031322

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: 02/17/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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