Dataset Information

Mucosa-Associated Microbiota in Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls.

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. DISCUSSSION:There are similar significant changes in bacterial genera in Barrett's esophageal mucosa, 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.

SUBMITTER: Peter S

PROVIDER: S-EPMC7473866 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Mucosa-Associated Microbiota in Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls.

Peter Shajan S Pendergraft Amanda A VanDerPol William W Wilcox C Mel CM Kyanam Kabir Baig Kondal R KR Morrow Casey C Izard Jacques J Mannon Peter J PJ

Clinical and translational gastroenterology 20200801 8

<h4>Introduction</h4>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.<h4>Methods</h4>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 ( ...[more]

PMID: 32955191

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Project description:AimTo investigate the microRNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett's esophagus.MethodsHigh throughput screening using TaqMan® Array Human MicroRNA quantitative PCR was used to determine expression levels of 754 microRNAs in distal esophageal mucosa (1 cm above the gastro-esophageal junction) from 16 patients who had undergone ablation of non-dysplastic Barrett's esophagus using argon plasma coagulation vs pretreatment mucosa, post-treatment proximal normal non-treated esophageal mucosa, and esophageal mucosal biopsies from 10 controls without Barrett's esophagus. Biopsies of squamous mucosa were also taken from 5 cm above the pre-ablation squamo-columnar junction. Predicted mRNA target pathway analysis was used to investigate the functional involvement of differentially expressed microRNAs.ResultsForty-four microRNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen microRNAs were differentially expressed between post-ablation neosquamous and post-ablation squamous mucosa obtained from the more proximal non-treated esophageal segment. Twelve microRNAs were differentially expressed in both neosquamous vs matched proximal squamous mucosa and neosquamous vs squamous mucosa from healthy patients. Nine microRNAs (miR-424-5p, miR-127-3p, miR-98-5p, miR-187-3p, miR-495-3p, miR-34c-5p, miR-223-5p, miR-539-5p, miR-376a-3p, miR-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These microRNAs were also more highly expressed in Barrett's esophagus mucosa than matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in the regulation of cell survival signalling pathways. Three microRNAs (miR-187-3p, miR-135b-5p and miR-31-5p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These miRNAs were expressed at similar levels in pre-ablation Barrett's esophagus mucosa, matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in regulating the expression of proteins that contribute to barrier function.ConclusionNeosquamous mucosa arising after ablation of Barrett's esophagus expresses microRNAs that may contribute to decreased barrier function and microRNAs that may be involved in the regulation of survival signaling pathways.

Dataset Information

Mucosa-Associated Microbiota in Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls.

Publications

Mucosa-Associated Microbiota in Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls.

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