# Microbiomic Mechanisms of Association between Childhood Social Determinants and Young-Adult Subclinical CVD

> **NIH NIH R03** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2022 · $78,657

## Abstract

PROJECT SUMMARY/ABSTRACT
Childhood exposure to adverse social determinants of health (SDoH) is highly prevalent in contemporary youth
and is linked in a dose-dependent manner with adult cardiovascular disease (CVD) rates. Metabolic and immune
dysfunction are thought to be involved, but many questions remain as to how SDoH get `under the skin' to
activate biological pathways leading to CVD. The human microbiome may be a key mediator of SDoH-CVD
associations and related disparities, but research in this area is sparse. Small studies indicate that the gut
microbiome varies across socioeconomic levels and can be modified by housing environments, social
connectedness, and psychosocial stress. Separately, experimental data demonstrate causal roles for the
microbiome in host immune function, metabolism, and atherosclerosis. However, lack of comprehensive data on
SDoH, the microbiome, and CVD phenotypes in disadvantaged populations is a critical barrier to understanding
potential links. Our long-term goal is to develop strategies to reduce the burden of SDoH-related CVD in
disadvantaged populations. The objective of the current proposal is to establish a biorepository and generate
pilot and feasibility data for a near-term R01 proposal in which we will aim to comprehensively assess
associations between early-life SDoH, the gut microbiome, and CVD risk indicators in young adults and further
examine causal mechanisms in a gnotobiotic mouse model. We propose an ancillary study of >1000 young
adults in the Fragile Families Study (FFS). FFS enrolled newborns in large US cities from 1998-2000, with
oversampling of infants born to unmarried, racial/ethnic minority, immigrant, and low-income parents.
Comprehensive, detailed SDoH, psychological, and behavioral data have been collected at birth and ages 1, 3,
5, 9, and 15 years, as well as genotype and genome-wide DNA methylation at ages 9 and 15 years. The NHLBI-
funded (R01 HL149869) examination at age 22 years will include similar measures plus detailed CVD risk factor
data and state-of-the-art carotid artery imaging to detect early atherosclerosis. For the current R03, we propose
to establish a gut microbiome repository from FFS participants, including stool DNA for shotgun metagenomic
analysis and fresh stool samples for gnotobiotic experiments, and to generate preliminary data through the
following Specific Aims: (1) Identify associations of early-life SDoH with the young-adult gut microbiota, and (2)
Identify gut microbiota variables associated with young-adult subclinical CVD, CVD risk factors, and epigenetic
age, in a subset of N=95 FFS participants, to inform design of the subsequent R01 proposal. The biospecimens
and data resulting from the proposed project will directly support successful transition of the PI to independent
funding, building on her K23-funded study of the gut microbiome as a contributor to CVD risk in early life. The
science proposed in the subsequent R01 will substantially advance our...

## Key facts

- **NIH application ID:** 10425095
- **Project number:** 1R03HL162767-01
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Amanda K Marma
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $78,657
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425095

## Citation

> US National Institutes of Health, RePORTER application 10425095, Microbiomic Mechanisms of Association between Childhood Social Determinants and Young-Adult Subclinical CVD (1R03HL162767-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10425095. Licensed CC0.

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