# Conserved Fetal Epigenomic and Metagenomic Signatures in a Primate Model of Maternal Obesity

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $645,963

## Abstract

Given the growing body of evidence that many (if not the vast majority) of chronic, non-communicable
disease have their origins in fetal life, understanding the in utero factors that impact fetal metabolism and
development are among the most important public health issues of our time. During the initial grant period, we
generated and published considerable data which (together with others work) collectively suggest that fetal
(re)programming of metabolic and developmental gene expression pathways occur via stable modification of
not only the epigenome, but the metagenome (e.g., the microbial community genetic repertoire). In the current
renewal, we propose a series of experiments that will considerably advance these findings.
 Why study the microbiome in our non-human primate model? Employing our non-human primate model,
we were the first to demonstrate that a high fat diet, and not obesity per se, drives both maternal and offspring
microbial dysbiosis. For several years we have developed and employed metagenomics to characterize the
early human developmental microbiome, and observed variation in its community membership and their
function by virtue of multiple factors. However, given the inherent confounding of human cohorts, it remains
unknown what the relative impact of maternal diet is on the early offspring microbiome, and whether this is
driven by host epigenomic modifications. Moreover, how this leads to lifelong metabolic disease is unknown.
 Based on our published and preliminary data from the initial grant period, our central hypothesis is that
under conditions of maternal high fat diet exposure in gestation and lactation, the offspring hepatic and
hypothalamic epigenome and the establishing microbiome undergo a series of highly predictive modifications.
These modifications result in meaningful functional alterations to the offspring metabolome as well as
transcriptome, resulting in both metabolic disturbances as well as behavioral modifications. While these
offspring modifications are not readily modifiable with an improved diet post-weaning, reversion of the dams
onto control diet just prior to pregnancy is largely restorative to her offspring. In order to prove this hypothesis,
we will execute four essential aims in our primate cohort. The net result of the completion of these aims will be
to first establish the conserved alterations to the fetal and juvenile gut and oral microbiome, alongside full
spectral metabolomics, to identify the stable and lasting metabolic (both host and bacterial) footprint of
maternal high fat diet exposure. By integrating our existing epigenomics data with the derived metagenomics
data, we will be able predict how these microbiome and metabolome variations in turn influence fetal and
offspring metabolic outcomes and phenotypic traits. After having spent over a decade establishing and
molecular characterizing the current NHP model, we are uniquely poised to now undertake complex integration
of our derived ...

## Key facts

- **NIH application ID:** 9991796
- **Project number:** 5R01DK089201-09
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Kjersti Marie Aagaard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $645,963
- **Award type:** 5
- **Project period:** 2012-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991796

## Citation

> US National Institutes of Health, RePORTER application 9991796, Conserved Fetal Epigenomic and Metagenomic Signatures in a Primate Model of Maternal Obesity (5R01DK089201-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991796. Licensed CC0.

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