Metabolic, Microbiome and Toxicant-Related Interactions (MATRIX)

EPA Grant Number: R836153C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R836153
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Center for Children’s Health, the Environment, Microbiome, and Metabolomics’ Center
Center Director: McCauley, Linda
Title: Metabolic, Microbiome and Toxicant-Related Interactions (MATRIX)
Investigators: Jones, Dean P. , Corwin, Elizabeth , Li, Shuzhao
Institution: Emory University
EPA Project Officer: Louie, Nica
Project Period: September 1, 2015 through August 31, 2019
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text |  Recipients Lists
Research Category: Health , Children's Health

Objective:

The overall goal of this project is to characterize the complex interactions of pre- and postnatal environmental toxicant exposures, microbiome composition, and associated metabolic pathways that underlie the development of preterm birth and neurodevelopmental delay.

Specific Aim 1: Characterize the metabolites and metabolic pathways that associate with preterm birth and neurodevelopmental delay.

Specific Aim 2: Characterize the metabolites and pathways that correlate with the maternal prenatal microbiome, maternal prenatal and infant postnatal environmental toxicant exposures, and the infant microbiome and neurodevelopmental delay.

Approach:

This project leverages the combined expertise of the members of this Center with the resources of two pillar studies – the recently initiated 5-year study assessing the maternal prenatal microbiome as predictive of birth outcomes in a large and socioeconomically diverse cohort of pregnant African American (AA) women; and the analytic and bioinformatic resources of Emory University’s NIH-funded Human Exposome Research Center (HERCULES) – in order to characterize the complex interactions of pre- and postnatal environmental toxicant exposures, microbiome composition, and associated metabolic pathways that underlie the development of two serious child health conditions, preterm birth and neurodevelopmental delay. 

This project will advance the science in this area by characterizing the following for 300 AA mother-infant pairs derived from the Parent Study: (1) the metabolites and metabolic pathways that associate with preterm birth and neurodevelopmental delay, and (2) the metabolites and pathways that correlate with the maternal prenatal microbiome (data from the Parent Study), maternal prenatal and infant postnatal environmental toxicant exposures (data from Project 1), and the infant microbiome and neurodevelopmental delay (data from Project 2). By unraveling these complex relationships, this project will contribute to the ability to predict these adverse outcomes and appropriately target preventive therapies.

Rationale:

Most complex health conditions do not have a single etiology, but rather develop from exposure to multiple exogenous and endogenous factors that interact to influence individual susceptibility. Failure to consider these multiple and complex interactions reduces the ability of health care providers to accurately predict the occurrence of disease and appropriately target preventive therapies.

Preterm birth and neurodevelopmental delay carry lifelong consequences for children and their families. Neither the occurrence of preterm birth nor neurodevelopmental delay is equally distributed within the US population. The incidence of preterm birth in Caucasian infants is 1:10, whereas it is 1:6 for AA infants, resulting in more than 30,000 AA infants born preterm each year in the United States. Neurodevelopmental delay is likewise more common in AA children, and racial disparities in neurodevelopmental delay persist or worsen across development, even when accounting for socioeconomic status and rates of preterm birth. Also more common among AA families are exposures to environmental toxicants, maternal prenatal infections and inflammation, and chronic stress – all independent risk factors for preterm birth and neurodevelopmental delay. Most recently, race-related differences in the vaginal microbiome have been identified as well, with AA women harboring vaginal microbial communities associated with higher risk of infection. Research to uncover the interactions between these factors and to identify the underpinning molecular pathways has barely begun. 

Publications and Presentations:

Publications have been submitted on this subproject: View all 10 publications for this subprojectView all 41 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 1 journal articles for this subprojectView all 6 journal articles for this center

Progress and Final Reports:

2016 Progress Report
2017 Progress Report


Main Center Abstract and Reports:

R836153    Center for Children’s Health, the Environment, Microbiome, and Metabolomics’ Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836153C001 Characterizing Exposures and Outcomes in an Urban Birth Cohort (CHERUB)
R836153C002 Microbiome, Environment, and Neurodevelopmental Delay (MEND)
R836153C003 Metabolic, Microbiome and Toxicant-Related Interactions (MATRIX)