# Esophageal Microbiome, Epithelial Gene Expression, and Response to Topical Swallowed Steroids in Pediatric Eosinophilic Esophagitis

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $259,500

## Abstract

Summary
Eosinophilic esophagitis (EoE) is an increasingly prevalent allergen-mediated clinico-pathologic
condition. It is characterized by the presence of esophageal symptoms and impaired esophageal
epithelial barrier in the setting of eosinophilic inflammation. The children with EoE suffer from
debilitating symptoms such as vomiting, feeding difficulties, inability to swallow, and failure to thrive.
Topical swallowed steroids (TSS) are the mainstay of EoE therapy and can lead to improvement in
symptoms, histologic remission, and restoration of the epithelial barrier function. However, over 50% of
children with EoE may not respond to TSS and continue to suffer from unremitting symptoms which can
negatively impact their quality of life. Additionally, the uncontrolled eosinophilic inflammation can further
compromise the esophageal epithelial properties and lead to sub-epithelial fibrosis resulting in
esophageal stricture and esophageal food impactions requiring emergent endoscopy or surgical
intervention. To date, very little is known about the factors associated with response to TSS in children
with EoE. In particular, the role of esophageal microbiome and how it interacts with the esophageal
epithelium to impact the response to TSS in children with EoE has not been studied. It is important to
understand this relationship as the rapid increase in the incidence and prevalence of EoE strongly
indicates that environmental factors such as esophageal microbiome may have an essential role in
modulating the treatment response in EoE. The objective of this application is to investigate the role of
the esophageal microbiome and its cross-talk with the host epithelium in TSS responders (EoE-TSSr),
TSS non-responders (EoE-TSSnr) and non-EoE controls. For the first time, it would determine whether
TSS therapy outcomes are derived in part by resident esophagus microbiota structure and function that
can potentially alter esophageal barrier integrity and immune function. Using a pediatric cohort of EoE-
TSSr, EoE-TSSnr and non-EoE controls we will: a) characterize the microbiome composition and
functional capability at the species level in the esophagus tissue samples, b) determine the mechanistic
association between active esophagus microbiome, host epithelium expression profiles, and TSS
therapy efficacy. The outcomes of this study will expand our understanding about the factors
associated with response to TSS in pediatric EoE. In the long term, this study will lay the foundation for
personalizing the care in pediatric EoE.

## Key facts

- **NIH application ID:** 10432560
- **Project number:** 1R21AI168832-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Girish Hiremath
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $259,500
- **Award type:** 1
- **Project period:** 2022-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432560

## Citation

> US National Institutes of Health, RePORTER application 10432560, Esophageal Microbiome, Epithelial Gene Expression, and Response to Topical Swallowed Steroids in Pediatric Eosinophilic Esophagitis (1R21AI168832-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10432560. Licensed CC0.

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