# Metabolomics of Food Allergen Immunotherapy

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $311,000

## Abstract

PROJECT SUMMARY
Rates of potentially life-threatening IgE mediated food allergy continue to rise, and therapeutic options are
limited. Understanding how to alter immune tolerance in patients with food allergy is paramount to the
development of new therapies. Two types of food allergen immunotherapy, oral immunotherapy (OIT) and
sublingual immunotherapy (SLIT), rely on the administration of gradually increasing amounts of allergen to
induce tolerance. For some children, these therapies can induce a state described as remission, where the
protection against allergic reactions lasts weeks to months after stopping therapy. While current research has
focused on the adaptive immune responses to immunotherapy, the immunologic milieu necessary for these
responses is not known. Using metabolomic profiling, the large-scale quantification of metabolites by mass-
spectrometry, we identified 3 major pathways (bile acids, arachidonic acids, and histidine metabolites) with
known roles in modulating T cell biology that differentiate children who develop remission versus those who do
not. The overall goal of this proposal is to determine the role that immunomodulatory metabolites play in the
remission of food allergies induced by immunotherapy. In Aim 1, we will validate the presence of protective
metabolomic signatures of bile acids, arachidonic acids, and histidine pathways in remission using samples
from an interventional trial of OIT in young children. We will then assess how these metabolites change with
immune biomarkers of remission (serology, basophil reactivity, and T cell cytokines). While there are many
similarities in the mechanisms of OIT and SLIT, there is growing evidence for differences in the
pathophysiology of remission induced by these two types of immunotherapy. Based on this, we will study the
immunometabolism of remission in SLIT in Aim 2. Using samples from an interventional trial of SLIT, we will
characterize the presence of these three immunomodulatory metabolite pathways in remission and assess
how these pathways relate to immune biomarkers of remission. Finally, we will compare the metabolomic
profiles of SLIT and OIT to identify shared and disparate pathways between the two types of therapy. We
anticipate that this work will identify mechanisms of allergic tolerance in immunotherapy and inform the
development of new therapies.

## Key facts

- **NIH application ID:** 10952507
- **Project number:** 1R21AI185550-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Yamini V Virkud
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $311,000
- **Award type:** 1
- **Project period:** 2024-06-03 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952507

## Citation

> US National Institutes of Health, RePORTER application 10952507, Metabolomics of Food Allergen Immunotherapy (1R21AI185550-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10952507. Licensed CC0.

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