Molecular Pathways: Pathogenesis and Clinical Implications of Microbiome Alteration in Esophagitis and Barrett Esophagus
Open accessAbstract
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. Clin Cancer Res; 18(8); 2138–44. ©2012 AACR.
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Two types of microbiota have been identified in the esophagus: Type I, present in healthy subjects, is characterized by a predominance of Gram-positive taxa (especially Streptococcus), whereas type II, associated with ERD and Barrett esophagus (BE), is constituted by a predominance of Gram-negative taxa, including Veillonella, Prevotella, Haemophilus, Neisseria, Rothia, Granulicatella, Campylobact
“two types of microbiota have been identified in the esophagus: Type I, present in healthy subjects, is characterized by a predominance of Gram-positive taxa (especially Streptococcus), whereas type II, associated with ERD and Barrett esophagus (BE), is constituted by a predominance of Gram-negative taxa”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [37]
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References 55 · Cited by 192
- Authors
- Yang, L., Francois, F., & Pei, Z.
- Affiliations
- VA NY Harbor Healthcare System (US)
- Authors' Affiliations: Departments of 1Medicine and 2Pathology, New York University School of Medicine; 3Department of Pathology and Laboratory Medicine, Department of Veterans Affairs New York Harbor Healthcare System, New York, New York
- Corresponding author
- Pei, Zhiheng
- Venue
- Clinical Cancer Research
- Published
- 2012-04-15
- Volume
- 18
- Issue
- 8
- Pages
- 2138-2144
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3725293
- OpenAlex
- W2113345423
- Cited by
- 192
- References
- 55
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 23 · 2023: 18 · 2022: 12 · 2021: 28 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 9 · 2016: 11 · 2015: 15 · 2014: 12 · 2013: 8 · 2012: 1
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA159036, K23CA107123, UH2CA140233, UH3CA140233)
- National Institute of Allergy and Infectious Diseases (R01AI063477)
- National Institute of Dental and Craniofacial Research (U19DE018385)
- Topics
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- esophageal microbiome, Barrett's esophagus, reflux esophagitis, esophageal adenocarcinoma, intestinal metaplasia, lipopolysaccharide, Gram-negative bacteria, Gram-positive bacteria, TLR4, NF-κB signaling, inflammatory cytokines, lower esophageal sphincter relaxation, cyclooxygenase-2, inducible nitric oxide synthase, chronic inflammation, tumor progression, biomarkers
- MeSH terms
- Adenocarcinoma, Barrett Esophagus, Esophageal Neoplasms, Esophagitis, Esophagus, Gastroesophageal Reflux, Humans, Inflammation, Lipopolysaccharides, Cytokines, NF-kappa B, Disease Progression, Toll-Like Receptor 4, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Nitric Oxide Synthase Type II, Metagenome
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