# The effects of a wild gut microbiome on mucosal immunity and disease

> **NIH NIH F30** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $50,520

## Abstract

Project Summary
The gut microbiota has a fundamental role in the development and stability of the host immune
system. Colonization by certain bacteria, and even individual species, can alter the course of
many infectious and inflammatory diseases. Our understanding of the immune consequences of
colonization by members of the gut microbiota is based primarily on laboratory mouse models.
Although this conventional approach has enabled detailed mechanistic studies on the immune
system, laboratory mice may not reflect the more complex diseases of humans and free-living
mammals in a natural environment. Here we present the use of a unique outdoor facility that
allows us to adapt established mouse models to study disease risk in a more natural environment.
Our preliminary data suggests that introduction of laboratory C57BL/6 mice to our facility
increases the presence and function of key immune cell populations coincident with microbiome
changes. The increase in circulating neutrophils and CD4+/CD8+ memory cells, reduction in naive
T cells, and increased expression of costimulatory molecules on antigen presenting cells, all
occurs in the absence of viral, bacterial or parasitic pathogen exposure. Detailed mechanistic
study of how a natural microbiota alters mucosal immunity and contributes to disease risk has yet
to be investigated. We therefore propose that gut wild microbiota enhances local innate immune
activation and promotes the host immune response towards a proinflammatory state. To test this
hypothesis, we propose three aims: 1) define the effect of the wild microbiota on T cell polarization
in the gut, 2) determine the role of the inflammasome in the enhanced immunity mediated by the
wild microbiota, and 3) determine whether Nod2−/− mice display immune dysregulation when
exposed to wild microbiome. Altogether, these studies would elucidate novel host-microbe
interactions and may provide innovative insight into how genetic susceptibility can contribute to
the development and maintenance of disease.

## Key facts

- **NIH application ID:** 9959183
- **Project number:** 5F30DK122698-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Frank Yeung
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2019-06-14 → 2022-06-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959183

## Citation

> US National Institutes of Health, RePORTER application 9959183, The effects of a wild gut microbiome on mucosal immunity and disease (5F30DK122698-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9959183. Licensed CC0.

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