# Gut-brain dysfunction following combined prenatal stressors: relevance for autism

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $104,861

## Abstract

SUMMARY OF WORK
This is a diversity supplement application for the following awarded project: Gastrointestinal issues
are extremely common in neurodevelopmental disorders like autism spectrum disorder (ASD), and
alterations of the gut microbiome and intestinal epithelial barrier have been reported in recent
studies. Environmental toxicant exposures early in life are increasingly implicated in
neurodevelopmental disorders such as ASD, including air pollution. There is strong evidence that
particulate matter (PM) in air pollution significantly impacts the gut microbiome and gut function of
directly-exposed humans and rodents. Less characterized is if PM exposure to pregnant females
alters the gut microbiome of offspring, though this is likely given evidence that the maternal gut
microbiome sets the trajectory of the newborn microbiome, especially with a vaginal delivery. To
study the impact of environmental pollutants on autism-like behaviors in mice, we developed a
novel model combining prenatal diesel exhaust particle (DEP) exposure throughout pregnancy
with maternal stress (MS) during the last trimester of gestation. Maternal stress is linked to autism
in several recent studies, which may be most harmful for populations made vulnerable by other
factors. We have demonstrated that combined prenatal DEP + MS produce striking communication
and social deficits early in life, and persistent cognitive deficits and increased anxiety into
adulthood, in male but not female offspring. Our preliminary data also show significant changes in
the composition of gut bacteria and gut structural changes in male offspring exposed prenatally to
DEP/MS compared to unexposed controls. Our goal is to test the hypothesis that gut microbiome
changes in pregnant dams following combined environmental exposures are transmitted to
newborn offspring and underlie the persistent behavioral abnormalities. Together these studies
will: (1) fully characterize the impact of prenatal environmental toxicant (DEP) exposure on
maternal and offspring microbiome development, (2) ascribe causality among microbiota changes,
gut epithelial structure/function and inflammation, and behavioral abnormalities in offspring, and
(3) establish the critical window(s) in which microbiome changes in offspring can be prevented or
reversed using interventions at birth vs. post-weaning. If successful they will significantly advance
our understanding of the emergence and causal link between gut dysbiosis and behavioral/brain
dysfunction in devastating disorders such as autism, and the role of environmental toxins in
inducing these changes, as well as suggest a potential therapeutic option and window for
treatment.

## Key facts

- **NIH application ID:** 10533404
- **Project number:** 3R01ES033056-02S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Staci D Bilbo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $104,861
- **Award type:** 3
- **Project period:** 2021-04-07 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10533404

## Citation

> US National Institutes of Health, RePORTER application 10533404, Gut-brain dysfunction following combined prenatal stressors: relevance for autism (3R01ES033056-02S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10533404. Licensed CC0.

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