# Influence of the perinatal microbiome on asthmatic phenotypes: associations with early life immune profiles

> **NIH NIH F30** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $43,862

## Abstract

PROJECT ABSTRACT
 The early life microbiome influences the development of atopic diseases, including asthma. Mechanistic
explanations for this influence include interactions of the gut microbiota with pattern recognition receptors of
the innate immune system, modulation of enzymes and transcription factors by bacterial metabolites, and
broad epigenetic alterations. While several studies have established influences of the gut microbiome on atopic
disease, it is becoming evident that other microbial sources can contribute to atopy. For example, we recently
demonstrated that cord blood microbiota contributes to asthmatic phenotypes, while studies from others have
also uncovered associations of the airway microbiome and the breast milk microbiota with atopic disease. Still,
the relative contributions and relationships of different microbiome compartments, as well as the mechanisms
by which they influence atopic priming, remain unclear. We propose a data-driven approach to: (1) determine
the influence of multiple compartments of the neonatal microbiome on development of asthmatic phenotypes,
and (2) characterize immune pathway alterations that prime asthmatic phenotypes and associate with
microbiome features.
 In Aim 1, we will characterize the microbiota of cord blood, gut, and maternal breast milk, and compare
these between infants who develop asthmatic phenotypes versus those who do not. Specifically, we will collect
cord blood at birth, and maternal breast milk as well as the child’s fecal samples at 1-month follow-up for
microbiome analyses. Microbiome profiles will be compared between subjects who exhibit the outcome metric
of repetitive wheeze at 1 year of age versus those who do not, and predictive models of outcome will be
created based upon taxonomic features. These results will reveal previously unexamined relationships
between multiple neonatal microbiome compartments and the development of asthmatic phenotypes.
 In Aim 2, we will characterize early life immune differences using transcriptomics and cytokine profiles
in asthmatic phenotypes, and elucidate immune alterations as a function of epigenetic perturbation and
microbiome composition. Specifically, mononuclear cells from cord blood and peripheral blood of infants will be
stimulated to activate T cells, and then we will compare resultant transcriptomic features and cytokine profiles
between infants who develop asthmatic phenotypes versus those who do not. We will further determine the
effects of epigenetic perturbation using a histone deacetylase inhibitor that is under investigation as a
therapeutic for asthma. Finally, in order to elucidate common pathways altered by HDAC inhibition and
microbial exposures, we will correlate immune features that are altered by HDAC inhibition with microbiome
features determined to be predictive of asthmatic phenotypes.
 In summary, we plan to elucidate the interplay of genes and environment that prime asthmatic
phenotypes.

## Key facts

- **NIH application ID:** 10690597
- **Project number:** 5F30HD102093-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Yishin Chang
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $43,862
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-05-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690597

## Citation

> US National Institutes of Health, RePORTER application 10690597, Influence of the perinatal microbiome on asthmatic phenotypes: associations with early life immune profiles (5F30HD102093-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10690597. Licensed CC0.

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