# Mechanisms by which intestinal bacteria contribute to maintenance of tolerance in food allergy

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $28,568

## Abstract

The prevalence of food allergy has experienced an unprecedented increase in Western societies, rising
by as much as 20% in a recent ten-year period. We have previously described a role for mucosa-
associated commensal bacteria in protection from allergic sensitization in mice. To understand how the
microbiota regulates allergic disease in humans, we colonized germ free mice with human bacteria from
the feces of healthy or cow’s milk allergic (CMA) infants. Our data shows that colonization with bacteria
derived from healthy human infant feces is sufficient to protect mice against sensitization to the cow’s
milk allergen b-lactoglobulin (BLG), whereas colonization with feces from human CMA infants fails to
protect. By analyzing operational taxonomic units (OTUs) differentially abundant between our human
fecal donors (4 healthy, 4 CMA) we have defined a microbial signature that distinguishes the CMA and
heathy populations in both the human donors and the colonized mice, emphasizing the clinical relevance
of our gnotobiotic model. RNASeq analysis of ileal intestinal epithelial cells revealed differentially
expressed genes (DEGs) that distinguished healthy- and CMA-colonized mice across all donors.
Correlation of ileal OTUs with DEGs in the ileum of healthy-colonized mice identified a Clostridial species,
Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate a
causal role for the healthy infant microbiota in protection against food allergy and suggest that
interventions that modulate bacterial communities may inform the development of novel therapeutic
strategies for this disease. In this proposal we will further refine our OTU signature and examine whether
the CMA infant microbiome is an atopic microbiome in Aim 1. Aim 2 will explore how healthy intestinal
bacteria influence the response to food allergens by examining their impact on innate lymphoid cell
function, early T/B priming and effector T cell differentiation and migration. The robust, pre-clinical
gnotobiotic models we describe will provide an ideal system in which to identify key host-microbial
interactions that contribute to the maintenance of tolerance to dietary antigen in food allergy.

## Key facts

- **NIH application ID:** 10142699
- **Project number:** 3R01AI146099-01A1S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** CATHRYN R NAGLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,568
- **Award type:** 3
- **Project period:** 2020-08-12 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142699

## Citation

> US National Institutes of Health, RePORTER application 10142699, Mechanisms by which intestinal bacteria contribute to maintenance of tolerance in food allergy (3R01AI146099-01A1S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10142699. Licensed CC0.

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