# Epidemiologic identification and mechanistic investigation of early life environmental risk factors for eosinophilic esophagitis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $696,693

## Abstract

Epidemiologic identification and mechanistic investigation of early life environmental risk factors for
eosinophilic esophagitis
ABSTRACT
Eosinophilic esophagitis (EoE) is a recently recognized immune-mediated disease defined by abnormal
infiltration of eosinophils into the esophageal mucosa, leading to failure to thrive, abdominal pain, vomiting, and
heartburn in children, and progressing to esophageal stenosis and food impaction in adults. Though initially
thought to be rare, the incidence and prevalence are rising dramatically, and over the past decade EoE has
rapidly become a major cause of upper gastrointestinal morbidity. Despite increases in the understanding of
the condition, it is currently not possible to determine why individual patients develop EoE. This is frustrating
for patients and practitioners alike. EoE is considered to be an immune/allergen-mediated disease, and
epidemiologic studies support a primarily environmental etiology. However, environmental risk factors have
not been extensively studied in EoE, and prior studies, including by our own group, are limited by a crude
assessment of exposures, recall bias, inability to assess fetal biomarkers, and lack of mechanistic
understanding. Our goal is to address this knowledge gap by using an innovative method to precisely measure
early life exposures in deciduous (primary, or “baby”) teeth that may be implicated in EoE development. Of
particular interest are early life antibiotic exposure and duration and intensity of breastfeeding (which can be
derived from barium levels in teeth). Increased antibiotic exposure and decreased breastfeeding have been
linked to risk of atopic diseases. Measuring selected environmental exposures in teeth has never been applied
to EoE, but we have documented the feasibility of this approach. This assessment, together with the use of
novel cellular and molecular techniques for elucidating the mechanisms underlying the effects of these early
life exposures, has the potential to greatly enhance our understanding of the pathogenesis of EoE. Our
hypothesis is that the risk of EoE related to early life exposures is primarily due to an impaired esophageal
epithelial barrier, and that genetic susceptibility will interact with the exposures to modify risk. The specific
aims are to 1) determine the association between early life antibiotic exposure and EoE; 2) determine whether
breastfeeding is associated with EoE, and evaluate whether the susceptibility genotype for CAPN14 modifies
the association between breastfeeding and EoE; and 3) determine the functional significance and mechanisms
of early life exposures on esophageal epithelial architecture and barrier function. To achieve these aims, we
will conduct a case-control study to characterize temporal exposures, and in parallel will perform mechanistic
analyses. This innovative, hypothesis-driven, and rigorously designed study will lead to robust and unbiased
results. It will be conducted by a multidisciplina...

## Key facts

- **NIH application ID:** 10214840
- **Project number:** 1R01ES031940-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Evan Samuel Dellon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $696,693
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214840

## Citation

> US National Institutes of Health, RePORTER application 10214840, Epidemiologic identification and mechanistic investigation of early life environmental risk factors for eosinophilic esophagitis (1R01ES031940-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10214840. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*