Molecular Pathways: Pathogenesis and Clinical Implications of Microbiome Alteration in Esophagitis and Barrett Esophagus
Year: 2012
Type: review
Abstract: Esophageal adenocarcinoma is preceded by the development of reflux-related intestinal metaplasia or Barrett esophagus, which is a response to inflammation of the esophageal squamous mucosa, reflux esophagitis. Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to the diverse microbial ecosystem or microbiome and inducing chronic inflammation. The esophageal microbiome is altered in both esophagitis and Barrett esophagus, characterized by a significant decrease in gram-positive bacteria and an increase in gram-negative bacteria in esophagitis and Barrett esophagus. Lipopolysaccharides (LPS), a major structure of the outer membrane in gram-negative bacteria, can upregulate gene expression of proinflammatory cytokines via activation of the Toll-like receptor 4 and NF-κB pathway. The potential impact of LPS on reflux esophagitis may be through relaxation of the lower esophageal sphincter via inducible nitric oxide synthase and by delaying gastric emptying via cyclooxygenase-2. Chronic inflammation may play a critical role in the progression from benign to malignant esophageal disease. Therefore, analysis of the pathways leading to chronic inflammation in the esophagus may help to identify biomarkers in patients with Barrett esophagus for neoplastic progression and provide insight into molecular events suitable for therapeutic intervention in prevention of esophageal adenocarcinoma development in patients with reflux esophagitis and Barrett esophagus.
Source: Clinical Cancer Research
Authors: Liying Yang, Fritz Francois, Zhiheng Pei
Institutions: VA NY Harbor Healthcare System, New York University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer, Crosstalk Among Oral & Gastrointestinal Soluble Innate Factors, HIV, & Microbes, H. PYLORI AND IL-1Beta IN ESOPHAGEAL ONCOGENESIS, Foregut microbiome in development of esophageal adenocarcinoma, Etiology & pathogenesis of chronic tonsillar hypertrophy, Foregut microbiome in development of esophageal adenocarcinoma
OpenAlex ID: W2113345423