# Prenatal maternal obesity and neurodevelopment: The mediating role of the microbiome and metabolome

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $710,874

## Abstract

Project Summary
Impaired emotion regulation (ER) is a risk factor for a wide range of neuropsychiatric conditions and safeguarding
its development could have important implications on mental health. Pre-pregnancy obesity has long been
associated with indicators of impaired ER in children – e.g., elevated mood symptoms, increased negative
emotional intensity, and increased rates of psychiatric disorders with ER deficits such as depressive and anxiety
disorders. Despite these well documented associations, mechanistic studies in humans that link pre-pregnancy
obesity with offspring ER development are scarce. Our proposal aims to address this research gap. We will
examine the overarching hypothesis that pre-pregnancy maternal obesity negatively influences offspring ER
development through its effects on the maternal gut microbiome and metabolome. Our innovative design
includes longitudinal assessments of the maternal microbiome and metabolome, repeated assessments of ER-
related brain systems in the offspring using fetal and infant MRI scans, and behavioral assays of ER in the
offspring through the first 24 months of life. Using these multimodal assessments and longitudinal design, we
will test whether (a) the maternal gut microbiome during gestation is influenced by maternal obesity; (b) the
maternal gut microbiome is associated with maternal metabolites within tryptophan and tyrosine metabolic
pathways; and (c) maternal metabolites in turn correlate with ER development measured with brain (fetal and
infant MRI) and behavioral correlates. Our study is uniquely positioned to address these aims leveraging an
ongoing human birth cohort study (HOPE cohort, supported by Duke University) of mother-infant dyads enriched
for obesity (50% of enrollees with pre-pregnancy BMI>=30, confirmed by medical record). The HOPE cohort
includes an extensive battery of biospecimens and clinical/demographic measures with pregnant women
enrolled during the first trimester gestation and their children followed into the first few years of life. With over 1
million children born yearly in the US to mothers who experienced pre-pregnancy obesity, the ER developmental
impact of pre-pregnancy obesity is a substantial and mounting concern – and disproportionately impacts low
income and minoritized populations. Mechanistic research in humans that links pre-pregnancy obesity with
offspring ER development and psychiatric risk is critical to advancing prevention efforts.

## Key facts

- **NIH application ID:** 10810401
- **Project number:** 1R01MH133313-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jonathan E Posner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $710,874
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810401

## Citation

> US National Institutes of Health, RePORTER application 10810401, Prenatal maternal obesity and neurodevelopment: The mediating role of the microbiome and metabolome (1R01MH133313-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10810401. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*