# Project 3: Interactions between microbial metabolites, airway pathogens and airway epithelial cell function

> **NIH NIH U19** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $294,538

## Abstract

PROJECT SUMMARY
 The early life environment modifies the risk for childhood allergic diseases, wheezing illnesses, and asthma,
and these diseases are less common in children who grow up on farms. Accordingly, in our studies of the
Wisconsin Infant Study Cohort ("WISC," funded by the AADCRC program), reductions in atopic dermatitis and
respiratory illnesses were related to the intensity of farm exposures during the prenatal and early postnatal
periods. Notably, allergies and asthma are rare in children in traditional agrarian (TA) settings (e.g., Amish
communities) with intense farm exposures. Early life microbial exposures and colonization are likely to contribute
to health benefits by promoting epithelial cell function and immune development. Certain commensal microbes
such as Corynebacterium sp. and Dolosigranulum pigrum are inversely associated with bacterial respiratory
pathogens and reduce the risks of viral wheezing illnesses and exacerbations of childhood asthma.
 These findings suggest that airway microbiomes of TA and healthy farm children will be a rich source
of microbes that can inhibit viral and bacterial pathogens, increase epithelial integrity, and prime anti-
pathogen responses. To test this hypothesis, we have established in vitro models of cultured airway epithelial
cells to determine mechanisms for interactions between airway bacteria, viral infections, and epithelial cell
composition and function. Our preliminary data indicate that TA children have microbiome community structures
enriched for "protective" commensal bacteria with distinct genetic features. Finally, we used single-cell
transcriptomics to identify characteristics of airway epithelial cells that are highly susceptible to infection with
rhinoviruses (RV), which commonly cause wheezing illnesses during childhood.
 This project will test for interactions between airway commensal bacteria, airway pathogens, and epithelial
cells. First, we will screen commensal bacteria from healthy TA and farm children for metabolites that inhibit viral
and bacterial pathogens. Second, we will culture and analyze nasal airway epithelial cells from TA, farm, and
non-farm children to determine whether environmental exposures lead to group-related differences in cell
composition, antiviral responses, and synthesis of antimicrobial peptides. Finally, we will analyze effects of
selected bacterial metabolites from TA and farm children on cultured airway epithelial cells to determine whether
they exert beneficial effects on anti-pathogen responses and inhibit T2 inflammatory pathways.
 The results of these studies could lead to new therapeutic approaches to bring some of the health benefits
associated with farm exposures to all children.

## Key facts

- **NIH application ID:** 10813835
- **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:** $294,538
- **Award type:** 5
- **Project period:** 2013-02-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813835

## Citation

> US National Institutes of Health, RePORTER application 10813835, Project 3: Interactions between microbial metabolites, airway pathogens and airway epithelial cell function (5U19AI104317-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10813835. Licensed CC0.

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