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Open Access 01-12-2016 | Research article

Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma

Authors: Ali H. Zaidi, Lori A. Kelly, Rachael E. Kreft, Mark Barlek, Ashten N. Omstead, Daisuke Matsui, Natalie H. Boyd, Kathryn E. Gazarik, Megan I. Heit, Laura Nistico, Pashtoon M. Kasi, Tracy L. Spirk, Barbara Byers, Emily J. Lloyd, Rodney J. Landreneau, Blair A. Jobe

Published in: BMC Cancer | Issue 1/2016

Abstract

Background

Toll-like receptors (TLRs) recognize known molecules from microbes and have an established role in tumorigenesis. Using a rat model of esophageal adenocarcinoma, and human clinical samples, we investigated genes central to TLR-mediated signal transduction and characterized the esophageal microbiome across the spectrum of esophageal adenocarcinoma carcinogenesis.

Methods

We surgically induced bile/acid reflux in rats and their esophagi were harvested at 40 weeks post-surgery. Tissue samples from the model were selected for gene expression profiling. Additionally, for rat and human samples microbiome analysis was performed using PCR-ESI-MS-TOF technology with validation by fluorescence in situ hybridization.

Results

Gene expression results in the rat model indicated a significant upregulation of TLRs 1-3, 6, 7 and 9 in EAC compared to normal epithelium. PCR-ESI-MS-TOF analysis revealed a prevalence of Escherichia coli in Barrett’s esophagus (60 %) and esophageal adenocarcinoma (100 %), which was validated by fluorescence in situ hybridization. In the human clinical samples, Streptococcus pneumonia was detected in high abundance in gastroesophageal reflux disease and Barrett’s esophagus (50–70 %) in comparison to tumor adjacent normal epithelium, dysplasia, and esophageal adenocarcinoma (20–30 %). E. coli was detected in the Barrett’s esophagus and esophageal adenocarcinoma groups but was absent in the tumor adjacent normal epithelium, dysplasia, and the gastroesophageal reflux disease groups.

Conclusions

We demonstrated an association between the TLR signaling pathway and E. coli hinting towards possible early molecular changes being mediated by microbes in the rat model of esophageal adenocarcinoma carcinogenesis. Studies on human clinical samples also corroborate results to some extent; however, a study with larger sample size is needed to further explore this association.

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Title: Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma
Authors: Ali H. Zaidi
Lori A. Kelly
Rachael E. Kreft
Mark Barlek
Ashten N. Omstead
Daisuke Matsui
Natalie H. Boyd
Kathryn E. Gazarik
Megan I. Heit
Laura Nistico
Pashtoon M. Kasi
Tracy L. Spirk
Barbara Byers
Emily J. Lloyd
Rodney J. Landreneau
Blair A. Jobe
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-016-2093-8

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