# Microbiota-dependent early life programming of gastrointestinal motility

> **NIH NIH F30** · UNIVERSITY OF CHICAGO · 2021 · $51,036

## Abstract

PROJECT SUMMARY/ABSTRACT
This project investigates the role of the early life gut microbiota in the development of the enteric nervous
system, which controls gastrointestinal (GI) motility. As the most common reason for referral to a
gastroenterologist, chronic motility disorders such as irritable bowel syndrome (IBS) cost the nation an
estimated $30 billion annually and reduce quality of life for millions of Americans. Though motility disorders are
generally first diagnosed and then managed in adulthood, retrospective patient accounts and several other
lines of evidence implicate early life microbiota-enteric nervous system (ENS) interactions in adult dysmotility.
Despite this evidence, however, no studies to date have mechanistically interrogated how disruptions to the gut
microbiota during early life influence the severity and reversibility of chronic dysmotility. However, our
preliminary data suggest the presence of a critical window of postnatal development, in which metabolites
produced by gut microbes affect Wnt signaling extracellular matrix (ECM) structures in the adult ENS and have
long-term implications for host motility. These findings lead us to hypothesize that 1) disruption or depletion of
gut microbes during a critical window of postnatal development impairs adult GI motility, and 2) these effects
are partially mediated by butyrate-induced epigenetic regulation of Wnt signaling affecting ENS maturation and
are limited after critical period closure by perineuronal net (PNN)-like ECM structures.
We will interrogate these hypotheses using controlled microbial manipulations at several developmental stages
in gnotobiotic and conventionally raised mouse models, coupled with functional motility assays, innovative
multiscale imaging modalities, and single cell transcriptomics and epigenomics. The proposed studies form an
integral part of a fellowship training plan, which takes advantage of state-of-the-art research facilities at the
University of Chicago Digestive Diseases Research Core Center, as well as the expertise of collaborators at
the University of Chicago, Argonne National Laboratories, and the Mayo Clinic. The collective resources and
expertise to be utilized in this training plan not only will be instrumental for the applicant's development as a
future physician-scientist, but will also provide insights into the fundamental significance of environmental
disturbances during development, and the relevance of such disturbances for GI health. We anticipate that
imprinting processes early in life may be reprogrammed by restoring key developmental factors, depending on
the age at which intervention occurs. Such insights will be critical for the prevention of motility disorders and for
developing effective therapies for the millions of patients whose quality of life is harmed by chronic dysmotility.

## Key facts

- **NIH application ID:** 10235548
- **Project number:** 1F30DK126309-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Mary Frith
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 1
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235548

## Citation

> US National Institutes of Health, RePORTER application 10235548, Microbiota-dependent early life programming of gastrointestinal motility (1F30DK126309-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10235548. Licensed CC0.

---

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