# Identification of Early Metabolomic and Immune Endotypes of Allergy and Asthma: An Integrated Multiomics Approach

> **NIH NIH K01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $161,835

## Abstract

PROJECT SUMMARY
Metabolic dysregulation due to in utero and early-life environmental exposures has lasting consequences on
the developing immune system and lung and that these changes underlie the pathobiology of childhood atopy
and wheeze. However, significant gaps remain in understanding the dysregulated metabolic-immune pathways
and mechanisms involved in early childhood atopy and wheeze. Our preliminary study of the infant untargeted
metabolome demonstrated that dysregulation in the unconjugated bilirubin (UCB) and lipid mediator's pathway
are associated with number of wheeze episodes in a dose-response manner, which suggests the involvement
of endogenous antioxidant and lipid mediator pathways. In another preliminary study of the infant immunome,
we demonstrated that two distinct infant immune response profiles to acute respiratory infection, with an
immune response pattern characterized by increased Type-2 and Type-17 and decreased non-interferon Type-
1 immune responses to with increased risk of recurrent wheeze. While these single omics studies can identify
dysregulated metabolites and immune-responses in wheeze phenotypes, they alone fail to capture the full
spectrum of underlying pathobiology. The integration of omics data has advanced the understanding of other
chronic disease pathogenesis, as it is likely to do for childhood atopy and wheeze. Therefore, we hypothesize
that the integration of early-life metabolome (including lipidome) and immunome can elucidate molecular
pathways relevant to atopy and wheeze development. To test this hypothesis, the candidate will capitalize on
existing carefully phenotyped population-based birth cohort of healthy infants (INSPIRE) and a replication
cohort from the NIH ECHO initiative (ECHO-CREW asthma consortium) and accomplish the following specific
aims: 1) To investigate whether increased unconjugated bilirubin (UCB) levels reduce early life atopy and
wheeze incidence by enhancing the bioavailability of pro-resolving lipid mediators and antioxidants and
decreasing pro-inflammatory lipid mediators, 2) To discover novel immunome profiles and network modules
that characterize atopy and wheeze phenotypes, and 3) To uncover novel metabolic-immune molecular
pathways associated with the development of atopy and wheeze phenotypes by integrating metabolome and
immunome data. Successful completion of these aims will: (1) provide novel insights into the role of the early-
life metabolome and immunome in the pathogenesis of atopy and wheeze and (2) identify targets for disease
prevention. The proposal builds on the candidate's previous work, expertise, and interest in systems
approaches to understand disease development. The goal of this career development proposal is for the
candidate to emerge as an independent investigator in the field of asthma and allergy with unique knowledge
and application of systems approaches to understand disease mechanisms. The candidate is in an outstanding
academic environment, h...

## Key facts

- **NIH application ID:** 10239084
- **Project number:** 5K01HL149989-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Kedir Nesha Turi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,835
- **Award type:** 5
- **Project period:** 2020-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239084

## Citation

> US National Institutes of Health, RePORTER application 10239084, Identification of Early Metabolomic and Immune Endotypes of Allergy and Asthma: An Integrated Multiomics Approach (5K01HL149989-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10239084. Licensed CC0.

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