# Project 2: Relating the functional capacities of the GI and nasal microbiomes to immune development in children from traditional and modern exposures

> **NIH NIH U19** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $328,512

## Abstract

PROJECT SUMMARY
 The prevalence of allergic disease has risen drastically worldwide since the 1980s, disproportionately
affecting racial minority and young children. Allergic diseases, including asthma, are disorders of the immune
system, which is shaped by pre- and postnatal exposures, particularly by early life microbial exposures and
colonization in the developing infant. There is a critical need to understand the impact of microbial colonization
and their functional capacity in early life and the mechanisms by which they regulate the development of healthy
immune systems. Notable exceptions to the increasing prevalence of allergic diseases include children living
on dairy farms, and particularly Amish families, who follow a traditional agrarian (TA) lifestyle, as increased farm
exposures or diverse microbes, have been associated with protection against allergic disease.
We will test the overall hypothesis that gut and airway microbes and products influence local and distal
immunological responses that regulate respiratory allergy and infections. This project will analyze longitudinally
collected blood, stool and nasal samples from the TA, farm, and non-farm groups (WISC+, from Project I) to
identify differences in the functional capacity of the microbiomes of WISC+ children. To accomplish this goal, we
will perform metagenomic, meta-transcriptomic and metabolomics on longitudinal samples from the WISC+
study. We will then perform an integrative analysis of these data together with the gene expression and DNA
methylation (DNAm) data from Project I to identify relationships between the gut and airway microbiomes,
immune development and the expression of respiratory illnesses and allergic sensitization. Finally, we will
analyze data from the MARI study to identify microbial genes associated with the outcomes of natural respiratory
infections (Project I, Aim 2). We will assess group differences in the baseline nasal microbial genetics and
functional capacities of TA children vs. suburban children without asthma vs. suburban children with asthma
(MARI) and compare baseline microbial gene expression to host cell gene transcription, DNAm and the number
and severity of respiratory illnesses. These experiments in WISC+ and MARI will also provide a list of “select
microbes” that are increased in abundance in the farm and TA groups and have genetic features or predicted
metabolites linked to low rates of illness and allergic sensitization, which will be provided to investigators in
Project III. This will allow us to identify and select bacteria/metabolites based on their association with the
development of vigorous immune responses in farming environments. Information gained from the integration of
multi-omic data outlined in this proposal will lead to evidence-based selection of candidate bacteria for the next
generation of probiotics, secondary metabolites that can inhibit pathogenic bacteria or viruses, or modulate host
epithelial or immune cells to ...

## Key facts

- **NIH application ID:** 10813829
- **Project number:** 5U19AI104317-12
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Irene M Ong
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $328,512
- **Award type:** 5
- **Project period:** 2013-02-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813829

## Citation

> US National Institutes of Health, RePORTER application 10813829, Project 2: Relating the functional capacities of the GI and nasal microbiomes to immune development in children from traditional and modern exposures (5U19AI104317-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10813829. Licensed CC0.

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