# Interactions Between the Microbiome, Immunity and Respiratory Health in Traditional Agrarian and Suburban children

> **NIH NIH U19** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $1,407,863

## Abstract

PROJECT SUMMARY
 Asthma is an immune-mediated disorder, and early life allergic sensitization (T2 inflammation) and
respiratory illnesses are the most common precursors to the development of lifelong asthma. With over 300
million patients affected worldwide, asthma is a significant health care burden and a lifelong illness for most
individuals. New information is needed to design preventive treatments, and answers may come from studying
children who grow up in farming or traditional agrarian (TA) environments, who have intense and unique microbial
exposures and are much less likely to develop allergic diseases and asthma. We hypothesize that TA microbial
exposures and colonization promote immune development and airway epithelial cell functions to reduce
the risks of respiratory illnesses, allergies and asthma.
 To test this hypothesis, we started the Wisconsin Infant Study Cohort (WISC) in 2013 and added a cohort of
TA families in 2018 to determine mechanisms for protection against allergic diseases and asthma. We find that
Wisconsin farm children have distinct gastrointestinal and nasopharyngeal microbiome features and unique gene
expression patterns in nasal airway epithelial cells at age 2 years. These findings correspond with lower rates of
atopic dermatitis, often a precursor to asthma and respiratory illnesses. The differences in immune and microbial
signatures are even more pronounced in TA children. The microbiota in TA children's stool and nasal secretions
are enriched for commensals that may promote immune development and reduce rates of allergic diseases and
respiratory illnesses. Notably, the bacterial species identified in the TA samples contain genes distinct from those
found in samples from the farm and non-farm children. We therefore propose that TA bacteria of the GI tract and
airways and their metabolites are mediators of protection from allergic diseases and will be a rich source to
determine the mechanistic pathways that promote health.
 To test our overall hypothesis, we propose three highly interactive projects. Project I will determine how TA
children differ in immune development, nasal airway epithelial cell profiles, and clinical outcomes related to
respiratory illnesses and allergic diseases. Project II will evaluate how TA children's distinct microbiota and
their metabolites relate to their unique patterns of immune development and the resulting clinical outcomes.
Project III will use in vitro models of airway epithelial cells to determine the mechanisms of TA microbial
metabolites that inhibit viral and bacterial pathogens and modify the immune and inflammatory responses of
airway epithelial cells.

## Key facts

- **NIH application ID:** 10813825
- **Project number:** 5U19AI104317-12
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** James E. Gern
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,407,863
- **Award type:** 5
- **Project period:** 2013-02-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813825

## Citation

> US National Institutes of Health, RePORTER application 10813825, Interactions Between the Microbiome, Immunity and Respiratory Health in Traditional Agrarian and Suburban children (5U19AI104317-12). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10813825. Licensed CC0.

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