Title of Project: Early-Life Metal Exposure and the Gut Microbiome and Metabolome in Childhood
Principal Investigator (MPI): Shoshannah Eggers, PhD, Manish Arora, BDS, MPH, PhD, FICD
Co-Investigators: Chris Gennings, PhD; Christine Austin, PhD; Jeremiah Faith, PhD; Douglas Walker, PhD; Robert O. Wright, MD, MPH
Project Period: January 18, 2021 – January 17, 2022
Pilot Award Amount: $70,000
Abstract: There is increasing recognition of the importance of the human microbiome in health and disease, yet little is known about the effects of environmental toxicant exposures on the development of the microbiome. Early life exposures to metals may program the composition and function of the gut microbiome into childhood, and affect downstream health and development through childhood and the life-course. The purpose of this study is to lay the foundation for a large study on the effects of early life mixed metal exposure on the gut microbiome in childhood, and assess the association between the metal-associated gut microbiome and metabolome. We will leverage the ongoing birth cohort, Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS). Deciduous teeth and blood samples have been collected and analyzed to measure time resolved exposure to multiple metals from the second trimester in utero, through 10yearsold. Stool samples are being collected from participants between 9-11years. Additional demographic data have also been collected. This proposal will fund the analysis of the gut microbiome in stool samples using whole genome shotgun sequencing (n=200), and stool metabolomics in a subset of samples (n=60). Tooth and blood metal exposure data will be linked to the microbiome data to estimate the effects of early-life and childhood metal exposure on the composition and function of the gut microbiome and metabolome in childhood. The proposed project will generate novel evidence in support of future larger grants, and provide valuable insight into the relationship between early-life mixed metal exposures and the gut microbiome in childhood, identifying critical windows of exposure to target in future policies and interventions.
Title of Project: A longitudinal exposomic analysis of breastmilk to determine associations between persistent pollutants, the microbiome and metabolites
Principal Investigator (PI): Ryan Walker, PhD
Co-Investigators: Dania Valvi, PhD; Doug Walker, PhD; Chris Gennings, PhD
Project Period: January 18, 2021 – January 17, 2022
Pilot Award Amount: $25,000
Abstract: Human breastmilk is a complex source of nutrition and is a critical components of growth and development. Exposure, via breastmilk, to persistent organic pollutants (POPs) [specifically perfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDE)] during a critical window of early life developmental programming could have lasting effects on future child health outcomes. Given that early chemical exposure and the development of the infant gut microbiome co-occur during a critical window of infant development, the relationships between POPs, bacteria, and metabolites present in breastmilk merit study. To date no studies have assessed the effect of accumulated PFAS and PBDE exposure in breastmilk on the breastmilk microbiome and its metabolites. We propose to leverage a pre-existing prospective birth cohort study and utilize banked maternal breastmilk samples from a subset of 22 participating mothers. We aim to determine 1] POP levels in prospectively collected breastmilk samples, 2a] if POPs in breast milk are associated with breastmilk microbiome and 2b] if POPs in breastmilk are associated with breastmilk metabolites. We will use untargeted high-resolution mass spectrometry (GC and LC-HRMS) to measure concentrations of known and uncharacterized POPs, annotate breastmilk metabolites and use targeted sequencing of the bacterial DNA to identify changes to breastmilk microbiota across time. To test relationships between chemicals, metabolites and bacteria, we will use weighted quantile sum (WQS) regression with a random subset ensemble step to construct a weighted index of quantile-scored breast milk metabolites or bacteria as related to individual breastmilk PFASs. This pilot proposal will demonstrate feasibility in applying untargeted exposomics to breastmilk, an understudied component of human development. Results from this pilot study will inform a planned R01 proposal with a larger cohort, with repeated breastmilk samples and child outcome measures, to comprehensively study for the first time a breastmilk exposome-microbiome-metabolome link and its association with child health outcomes.
Title of Project: Community-Led Investigation of Air Quality and Environmental Injustice in Proximity to Two Waste Transfer Stations in Jamaica, Queens
Principal Investigator (MPI): Maida P. Galvez, MD, MPH; Luz Guel; Andrea Scarborough; Dawn Roberts Semple, Ph.D; Rebecca Bratspies
Co-I: Danielle Dubno-Hammer
Project Period: January 18, 2021 – January 17, 2022
Pilot Award Amount: $25,000
Abstract: When Mayor Giuliani closed the Fresh Kills landfill on Staten Island in the late 1990s, Southeast Queens found itself hosting a growing cluster of private waste transfer stations to process and export garbage to out-of-state landfills. Without a plan to deal with the massive flow of daily trucked trash, the city allowed these heavy industrial facilities to locate in close proximity to homes, parks, and schools in predominantly Black and Brown residential neighborhoods, such as Jamaica, Queens. Residents who live near the two waste transfer stations experience foul odors, diesel exhaust, waste blowoff and leachate, noise, and disruption from these facilities and trucks on a daily basis. In summer, the stench emanating from these waste transfer stations is so unbearable that residents are unable to use their backyards or open their windows. These waste transfer stations are legally obligated to comply with permit restrictions crafted to prevent them from negatively impacting the health and welfare of those living adjacent to the facility. Community science is a novel approach used to address sources of local pollution by in powering community members to lead research that directly affects their community. This pilot project will bring together scientists, community members, and lawyers for an interdisciplinary research collaboration to: 1) build capacity of frontline communities to identify and analyze the frequency and severity of permit violations by providing them with training to lead research, and utilize crowd-sourcing tools to document odor concerns and PM2.5 measurements within a one-mile radius of the stations; 2) inpower residents to use findings to recommend modifications that promote the use of best practices in the facilities’ siting, design, and operation. This project will enable the community to mobilize innovative strategies to ensure proper management of the waste facilities, which will improve their health and quality of life.
Title of Project: Characterizing critical windows of developmental metal mixture effects to kidney development and maturation using transgenic zebrafish
Principal Investigator (MPI): Weibin Zhou, PhD and Alison Sanders, PhD
Co-Investigators: Chris Gennings, PhD; Jaime Chu, PhD
Period: January 18, 2021 – January 17, 2022
Pilot Award Amount: $25,000
Abstract: The zebrafish is a valuable vertebrate model for developmental kidney research. A majority of prior work has focused on the zebrafish pronephros, which comprises only two nephrons and is structurally simpler than the mesonephros of adult fish and the metanephros of humans and other mammals. To evaluate the zebrafish system for more complex studies of kidney development and maturation following toxicant-induced injury, we will investigate the development and post-injury response of the mesonephros in zebrafish Danio rerio. We will examine kidney developmental effects of toxic metals using population-relevant doses. Our population-based preliminary data show that common environmental chemicals such as arsenic (As), lead (Pb), cadmium (Cd), chromium (Cr), and lithium (Li) influence kidney function as early as adolescence, and potentially play a role in early onset of CKD. However, a comprehensive analysis of the effects of chemical toxicant mixtures on kidney development and function throughout the life course remains unknown. Here, we propose to expand prior work to test our hypothesis that developmental nephrotoxicant mixtures, during critical windows of mesonephric kidney development (equivalent to metanephric development in the 2nd and 3rd trimester in humans) program altered histology, gene expression, and functional measures in the developing kidney. We hypothesize that metal mixtures disrupt key genes involved in nephron development as well as glomerular and tubular formation injury and alter glomerular and tubular regeneration following injury. Our team comprises expertise in metals toxicology (mPI Sanders and co-I Chu), zebrafish developmental biology (mPI Zhou and co-I Chu), and chemical mixtures risk assessment and biostatistics (co-I Gennings). Our findings will provide critical preliminary data and demonstrate capacity to succeed as a transdisciplinary team for future mechanistic and translational R01 proposals.
Title of Project: Determining exposure to mixtures of per- and polyfluoroalkyl substances and its association with gestational diabetes in an ethnically diverse U.S. population
Principal Investigator: Damaskini Valvi, MD, MPH, PhD & Syam Andra, PhD
Co-Investigators: Rosalind J Wright, MD, MPH; Elena Colicino, PhD
Project Period: January 18, 2021 – January 17, 2022
Pilot Award Amount: $25,000
Abstract: Per- and polyfluoroalkyl substances (PFASs) are chemicals used in a wide range of consumer products. Previous evidence supports an association of PFASs exposures with impaired glucose tolerance and gestational diabetes, among other adverse health outcomes. However, underlying mechanisms are not fully understood, and previous studies have focused on few PFASs while the average population is possibly exposed to hundreds of P FASs. Moreover, minority racial groups that may be disproportionally affected by PFASs exposures are underrepresented in the literature. Therefore, we propose to leverage the unique resources of the ethnically diverse U.S. mother-child cohort study ‘Programming of Intergenerational Stress Mechanisms’ (PRISM) to characterize the PFASs mixture in serum of pregnant women (Aim 1) and its association with impaired glucose tolerance during gestation (Aim 2a). We will further examine maternal inflammation as a mechanism of PFASs toxicity in pregnancy (Aim 2 b). For Aim 1, we propose to: (a) use our proficiency test -validated, low -volume and high -sensitive targeted liquid chromatography-tandem mass spectrometry (LC -MS) assay for absolute quantification, and (b) develop a new, cost -efficient, untargeted low -resolution LC-MS assay that can screen up to 1 00 PFAS suspects, providing the most comprehensive characterization of PFASs in human serum up to date. Subsequently in Aim 2, we will evaluate the associations of individual PFASs and the PFASs mixtures with maternal health outcomes (i.e. impaired glucose tolerance and inflammation) using a state -of-the- art statistical approach for analyzing exposure mixtures that accounts for both additive and multiplicative effects between individual PFASs. Findings will support a planned R01 submission that aims to leverage the data -rich PRISM mother-child cohort resource to advance the knowledge about the effects of classical and emerging PFASs and the PFASs mixture in pregnant women by providing a comprehensive characterization of PFASs exposure and potential mechanisms of toxicity using innovative ‘omics’ biomarkers.