# Maternal gut microbiota in fetal programming of neurodevelopment and related disorders

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $538,938

## Abstract

Project Summary
Social interaction is fundamental to the most universal of human experiences, such as family life, business, and
romance; however, social dysfunction is a debilitating hallmark of major neurodevelopmental disorders, including
autism and schizophrenia. Despite significant advances, the mechanisms underlying social dysfunction and
other core behavioral symptoms associated with neurodevelopmental disorders remain elusive and interventions
limited. There is growing consensus in support of a ‘two hit’ hypothesis for neurodevelopmental disorders, in
which a secondary environmental factor initiates abnormal developmental programming that contributes to
behavioral dysfunction in genetically predisposed individuals. Among environmental factors, diet is a leading
factor contributing to host disease susceptibility. Notably, diet is the chief determinant of host gut microbiome
composition. Through modulation of host immune function, and even the brain and behavior, the gut microbiome
is emerging as a major influence on host health and well-being. Disruption, or ‘dysbiosis,’ of the gut microbiome
is, in turn, associated with several common inflammatory disorders, including inflammatory bowel disease and
metabolic syndrome. Dysbiosis is also observed in neuropsychiatric patient populations, who have a high rate
of gastrointestinal symptom comorbidity; yet, the relationship between dysbiosis of the gut microbiome and
neurodevelopmental or other neuropsychiatric disorders is poorly understood. In this project, we will determine
if maternal high-fat diet (MHFD)-induced dysbiosis of the gut microbiome during pregnancy contributes to
descendant neurobehavioral dysfunction and the underlying mechanisms. Previously, we reported that MHFD
induces dysbiosis of the male offspring gut microbiome as well as social dysfunction and underlying deficits in
synaptic plasticity in the social reward circuit. Recently, we identified a sexually dimorphic effect of MHFD on
offspring behavior–stronger social deficits are evident in males versus females–however, we observed dysbiosis
of both the male and female MHFD offspring gut. We reasoned that if the maternal gut microbiome is causally
related to offspring social dysfunction, then enduring dysbiosis of the female MHFD offspring gut microbiome in
the F1 generation may be sufficient to impair neurodevelopment and behavior in F2 males. Indeed, we observed
robust social dysfunction in male, but not female, F2 offspring. Here, we will test the hypothesis that HFD-induced
dysbiosis of the maternal gut microbiome drives abnormal fetal programming in F1 offspring that underlies social
dysfunction in both F1 and F2 males. In Aim 1, we will ask how HFD/MHFD affects remodeling of the P/F1
maternal gut microbiome during pregnancy. In Aim 2, we will determine the effects of HFD/MHFD on maternal
immune function, fetal immune imprinting, and the embryonic brain. In Aim 3, we will determine if modulation of
the maternal gut micro...

## Key facts

- **NIH application ID:** 10907608
- **Project number:** 5R01HD109780-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Shelly A Buffington
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $538,938
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907608

## Citation

> US National Institutes of Health, RePORTER application 10907608, Maternal gut microbiota in fetal programming of neurodevelopment and related disorders (5R01HD109780-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10907608. Licensed CC0.

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