Barrett's esophagus and esophageal cancer: Links to microbes and the microbiome.

Abstract

Esophageal cancer represents a major problem globally, with an estimated 398,000 esophageal squamous cell cancers (ESCC) and 52,000 esophageal adenocarcinomas (EAC) diagnosed worldwide in 2012 [1]. In the United States, EAC is more common than ESCC, and EAC in the US increased dramatically between 1997 and 2006 before stabilizing [2]. Furthermore, esophageal cancer remains particularly deadly, with a five-year survival rate of less than 20% [3]. EAC is thought to arise from Barrett’s esophagus (BE), a metaplastic differentiation from normal squamous epithelium to a columnar phenotype. Accepted risk factors for BE and progression to EAC include age, male sex, obesity, gastroesophageal reflux disease (GERD), and smoking [4, 5]. Unfortunately, less is known about the association between esophageal dysbiosis, inflammation, and the pathogenesis of BE and EAC. Most of the existing data on esophageal microbiota in BE and esophageal cancer are derived from small cross-sectional studies with limited information on causality. As such, this represents an important area for future research because changes in the esophageal microbiota may relate to modifiable factors such as antibiotic use and proton pump inhibitors (PPIs). The esophageal microbiota was initially thought to be primarily related to transient esophageal exposure to the oral microbiota [6], but more recently, culture-independent studies have shown the esophageal microbiota to represent its own niche [7]. In addition to swallowed oral bacteria, the esophagus is also exposed to refluxed gastric microbes, and while the esophageal microbiota resembles both oral and gastric microbiota, it is equal to neither [7, 8]. This review provides an overview of differences that have been described between the normal esophageal microbiota, BE, and EAC. We also discuss novel approaches to esophageal microbial sampling and consider clinical exposures that may alter the esophageal microbiota.