# Project 1: Role of Microbiota and Myeloid cells in Mouse Models of Barretts Esophagus

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $325,042

## Abstract

SUMMARY
The rapid increase in developed countries over the past 30 years in esophageal adenocarcinoma (EAC) suggests strongly
environmental influences. Barrett’s esophagus (EAC), a precursor lesion for EAC, is increasing and associated with
alterations in esophageal microbiota. Obesity, another risk factor for EAC, is associated with an altered gut microbiome.
Gut bacteria are able to promote inflammation and cancer through activation of myeloid cells that contribute to
regeneration and immunosuppression. In preliminary studies, we have examined microbiota and myeloid cells in our L2-
IL-1β mouse model of BE. This mouse model shows alterations in the GE junction microbiome at 12 months compared to
WT mice, and housing in germ-free (GF) conditions leads to reductions in inflammation, metaplasia and dysplasia.
Under SPF conditions, L2-IL-1β mice fed a high fat diet (HFD) show alterations in the microbiome and increased GE
junction tumors. GEJ metaplasia and dysplasia are also accelerated by treatment with proton pump inhibitors (PPIs),
which alters gastric microbiota, and by IL-8 expression, which mediates myeloid responses to microbes. Finally, we have
developed tools (HDC-EGFP and HDC-DTR mice) that allow us to track or ablate immature myeloid cells/MDSCs that
respond to microbes and promote gastrointestinal tumors. We propose 3 specific aims: (1) Define the role of gut
microbiota in BE/EAC using the L2-IL-1b mouse model. The GE junction microbiota will be analyzed during disease
progression using 16S rRNA sequencing, and the role in EAC determined by GF housing or antibiotic suppression, as well
as by colonization with defined flora. (2) Do obesity and PPIs promote BE/EAC in part through microbiota? We will
examine the effect of bacterial eradication on BE progression by HFD or PPIs. We will examine changes in microbiota in
obese or slender BE patients. (3). Do bacteria induce BE/EAC primarily through myeloid cells? We will examine changes
in myeloid cell trafficking to the GEJ in L2-IL-1β mice in response to microbiota and IL-8 using HDC-EGFP crosses, and
assess their functional role through ablation and adoptive transfer. Taken together, these studies will define the
potential role of microbiota in BE/EAC progression.

## Key facts

- **NIH application ID:** 10183178
- **Project number:** 5U54CA163004-10
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Timothy Cragin Wang
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $325,042
- **Award type:** 5
- **Project period:** 2011-09-26 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183178

## Citation

> US National Institutes of Health, RePORTER application 10183178, Project 1: Role of Microbiota and Myeloid cells in Mouse Models of Barretts Esophagus (5U54CA163004-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10183178. Licensed CC0.

---

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