# Integrating the genome, metabolome, and microbiome for childhood asthma: Risk and endotypes

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $109,350

## Abstract

PROJECT SUMMARY
Childhood asthma is the most common chronic respiratory condition in the U.S. While
epidemiological studies have identified risk factors (e.g., severe bronchiolitis) for childhood
asthma, the underlying mechanisms of asthma development (and its different phenotypes)
remain poorly understood. This major knowledge gap has hindered efforts to develop asthma
prevention strategies. The 35th Multicenter Airway Research Collaboration (MARC-35) study
(U01AI087881; Camargo, PI) is an ongoing 17-center cohort study that enrolled 921
hospitalized infants with bronchiolitis (median age, 3 months) during 2011-2014. In this
racially/ethnically- and geographically-diverse cohort, investigators have collected high-quality
biospecimens, including nasopharyngeal airway and blood samples at the index hospitalization.
Follow-up data include biannual parent interviews, medical record reviews, and in-person exam
at age 6 years, with ~80% follow-up to date. The present K01 project would extend this large
well-characterized bronchiolitis cohort by integrating genome, metabolome, and microbiome
(both 16S rRNA gene and metagenomic sequencing) data, which will not only elucidate the
mechanisms of incident asthma but also identify its endotypes. In Aim 1, we will determine the
integrated relationships of host genome and nasopharyngeal airway metabolome in infancy with
asthma development by age 6 years. In Aim 2, we will determine the integrated relationships of
host genome and nasopharyngeal airway microbiome (both structure and function) in infancy
with the risk of developing asthma by age 6 years. Finally, in Aim 3, we will identify clinically-
relevant endotypes of childhood asthma by integrating clinical, immunological (e.g., specific IgE,
25OHD, cytokines), and multi-omics data (i.e., host genome, serum metabolome, and airway
microbiome) at age 6 years. Our pilot data provide compelling support to the proposed work.
This K01 project will provide a unique opportunity to define the pathobiology of incident asthma
through examining the integrative role of genome, metabolome, and microbiome. Furthermore,
we will also define childhood asthma endotypes by leveraging multi-omics data in the
comprehensively-phenotyped MARC-35 cohort. These findings will lead to the development of
endotype-specific prevention strategies for asthma (e.g., through modulation of metabolism
pathways and microbiome) during early childhood. The mentoring team consists of NIH-funded
researchers with international expertise in all relevant fields. The study matches well with the
2017 NIAID Strategic Plan, which both ultimately aim to prevent allergic diseases, such as
asthma.

## Key facts

- **NIH application ID:** 10766244
- **Project number:** 5K01AI153558-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Zhaozhong Zhu
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $109,350
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10766244

## Citation

> US National Institutes of Health, RePORTER application 10766244, Integrating the genome, metabolome, and microbiome for childhood asthma: Risk and endotypes (5K01AI153558-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10766244. Licensed CC0.

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