# Targeting microbial dysbiosis in Food Allergy to restore tolerance

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $601,609

## Abstract

ABSTRACT
Food allergy (FA) has become a public health concern, affecting a sizeable segment of the population. Despite
the alarming increase in its prevalence, efforts to contain the FA epidemic have been stymied by the limited
understanding of disease pathogenesis, especially the role in this process of early life gut dysbiosis. In that
regard, our studies have established a critical role for immunomodulatory Clostridiales and Bacteroidales species
in enforcing immune tolerance to FA by inducing the differentiation of RORgt+ Treg cells, which act to suppress
FA. Early life expansion of RORgt+ Treg cells is induced by the bloom in Clostridiales and Bacteroidales species
during weaning from maternal milk to solid food. This expansion is counter-regulated by resistin-like molecule
beta (RELMb), which is elevated in FA subjects and mice. Accordingly, the focus of this proposal is to elucidate
the mechanisms by which early life dysbiosis promotes FA and its long-term implications in terms of disease
persistence and response to microbial therapy. We hypothesize that the microbial and immunological changes
ushered by weaning early in life provide a window of opportunity for tolerance induction to solid food in a process
regulated by RELMb, whose dysregulation by dysbiosis promotes FA (Aim 1). We also hypothesize that the
ineffective differentiation of RORgt+ Treg cell populations and the reciprocal emergence of Th2 cell-like Treg
cells, an imbalance we have identified to play a fundamental role in FA, acts to promote disease pathogenesis
by licensing IgE anti-food and anti-bacterial antibody responses (Aim 2). Finally, we hypothesize that products
and metabolites of individual immunomodulatory bacterial strains, including Toll-like receptors activators, aryl
hydrocarbon receptor ligands and secondary bile acids, act to enforce oral tolerance in FA by promoting RORgt+
Treg cell differentiation (Aim 3). The proposed studies will provide fundamental new insights relevant to the
pathogenesis of FA and offers novel opportunities in early life disease intervention and therapy.

## Key facts

- **NIH application ID:** 10359843
- **Project number:** 5R01AI158814-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Talal Amine Chatila
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $601,609
- **Award type:** 5
- **Project period:** 2021-02-25 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359843

## Citation

> US National Institutes of Health, RePORTER application 10359843, Targeting microbial dysbiosis in Food Allergy to restore tolerance (5R01AI158814-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10359843. Licensed CC0.

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