# Project 3: Application of the Microbiome and Microenvironment to Novel Non Endoscopic Screening and Surveillance in Barrett's Esophagus

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $474,801

## Abstract

PROJECT 3 SUMMARY 
The incidence of esophageal adenocarcinoma (EAC) has risen nearly ten-fold over the past several decades, 
and the prognosis for EAC remains poor. During this time period, the GI microbiome has undergone a 
significant shift with the advent of antibiotics and the progressive decline in Helicobacter pylori infection rates, 
and there is increasing evidence that bacteria play an important role in GI cancers. However, the contribution 
of the esophageal microbiome to Barrett’s esophagus (BE) and EAC is not understood, and likely involves a 
complex relationship with the epithelium, microenvironment and gastro-esophageal reflux. Filling this gap in 
knowledge is critical to the development of rational cancer prevention strategies; the current paradigm, which 
relies on clinical suspicion to identify patients for endoscopy to screen for BE, has been unsuccessful and 
misses most patients who go on to develop EAC. The esophageal microbiome in BE is heavily populated with 
Gram-negative bacteria, which may drive a chronic inflammatory state. We have found high abundance of 
Fusobacterium nucleatum in EAC, and previous work by our team showed that F. nucleatum has proneoplastic 
effects in the colon. Further, in preliminary data we found that BE patients have alterations in specific taxa in 
the oral microbiome, a potential biomarker for BE. In Project 3 we propose to build directly on Projects 1 and 2 
to elucidate the relationship between the microbiome, inflammation, and the microenvironment in BE and EAC, 
with the end goal of developing a non-endoscopic testing strategy based on pathogenic factors to identify 
patients at highest risk for EAC. To accomplish this we will enroll 100 patients with known BE (50 with 
dysplasia or EAC) and 50 subjects without BE undergoing upper endoscopy. Prior to endoscopy each subject 
will undergo three minimally invasive potential screening and surveillance tests: saliva (oral microbiome), 
breath test (exhaled volatile organic compounds), and tethered capsule sponge sampling (methylated DNA 
markers). We will then address the following Specific Aims: 1) To assess the relationship between the 
microbiome (using 16S rRNA gene sequencing) and tissue inflammation (using RNA-Seq) in Barrett’s 
progression to EAC. We will also explore the oral microbiome and exhaled volatile organic compounds as 
potential biomarkers. 2) To determine how bile acid composition impacts the microbiome and tissue 
inflammation in BE. We will also assess the relationship between these factors and methylated DNA markers. 
3) To develop a non-endoscopic, biologically-based screening and surveillance strategy for BE. We will 
evaluate these novel tests in combination with clinical and anthropometric factors to describe an optimal 
strategy for BE screening and monitoring. We hope that this will lead to development of a testing approach that 
is highly acceptable to patients, is cost-effective, and can be easily translated to t...

## Key facts

- **NIH application ID:** 10183180
- **Project number:** 5U54CA163004-10
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Julian Abrams
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,801
- **Award type:** 5
- **Project period:** 2011-09-26 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183180

## Citation

> US National Institutes of Health, RePORTER application 10183180, Project 3: Application of the Microbiome and Microenvironment to Novel Non Endoscopic Screening and Surveillance in Barrett's Esophagus (5U54CA163004-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10183180. Licensed CC0.

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