Mucosa-Associated Microbiota in Barrett’s Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared with Healthy Controls

Authors

Shajan Peter, University of Alabama, BirminghamFollow
Amanda Pendergraft,, University of Alabama, Birmingham
William VanDerPol, University of Alabama, Birmingham
Mel Wilcox, University of Alabama, Birmingham
Kondal R. Kyanam Kabir Baig, University of Alabama, Birmingham
Casey Morrow, University of Alabama, BirminghamFollow
Jacques Izard, University of Nebraska-LincolnFollow
Peter J. Mannon, University of Alabama, BirminghamFollow

ORCID IDs

Izard https://orcid.org/0000-0002-5904-5436

Document Type

Article

Date of this Version

2020

Citation

Clinical and Translational Gastroenterology (2020) 11: e00199.

doi: 10.14309/ctg.0000000000000199

Comments

License: CC BY-NC-ND 4.0

Abstract

Introduction: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett’s microbiota could link to risk factors, providing risk of progression to neoplasia.

Methods: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria and analyzed by 16S ribosomal ribonucleic acid V4 gene DNA sequencing. Taxa composition was tested using a generalized linear model based on the negative binomial distribution and the log link functions of the R Bioconductor package edgeR.

Results: The microbe composition of paired samples (disease vs nondisease) comparing normal esophagus with intestinal metaplasia, low grade dysplasia, high grade dysplasia, and adenocarcinoma showed significant decreases in the phylum Planctomycetes and the archaean phylum Crenarchaeota (P < 0.05, false discovery rate corrected) in diseased tissue compared with healthy controls and intrasample controls (gastric juice and unaffected mucosa). Genera Siphonobacter, Balneola, Nitrosopumilus, and Planctomyces were significantly decreased (P < 0.05, false discovery rate corrected), representing < 10% of the entire genus community. These changes were unaffected by age, tobacco use, or sex for Crenarcha.

Discussion: There are similar significant changes in bacterial genera in Barrett’s esophagealmucosa, dysplasia, and adenocarcinoma compared with controls and intrapatient unaffected esophagus. Further work will establish the biologic plausibility of these specific microbes’ contributions to protection from or induction of esophageal epithelial dysplasia.

Includes supplemental files.