Potential Role of the Microbiome in Barrett's Esophagus and Esophageal Adenocarcinoma

Abstract

Esophageal adenocarcinoma and its precursor Barrett's esophagus have been rapidly increasing in incidence for half a century, for reasons not adequately explained by currently identified risk factors such as gastroesophageal reflux disease and obesity. The upper gastrointestinal microbiome may represent another potential cofactor. The distal esophagus has a distinct microbiome of predominantly oral-derived flora, which is altered in Barrett's esophagus and reflux esophagitis. Chronic low-grade inflammation or direct carcinogenesis from this altered microbiome may combine with known risk factors to promote Barrett's metaplasia and progression to adenocarcinoma.

Keywords: Barrett’s esophagus; Esophageal adenocarcinoma; Gastroesophageal reflux disease; Human microbiome.

Figures

Figure 1

Factors promoting Barrett's esophagus and esophageal adenocarcinoma. Chronic low grade inflammation of the gastric cardia, from a combination of factors including reflux, diet and an altered microbiome, promotes stem cell proliferation and intestinal metaplasia, leading to Barrett's esophagus, which in some cases can progress to esophageal adenocarcinoma

Figure 2

Historical trend of esophageal adenocarcinoma incidence. Esophageal adenocarcinoma began dramatically increasing in incidence in the 1960s, with a rise in Barrett's esophagus presumably preceding this by at least 5-10 years. This predates the increasing incidence of known risk factors for esophageal adenocarcinoma, including gastroesophageal reflux disease and obesity, but coincides with major changes in the upper gastrointestinal microbiome.