The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma

The incidence of esophageal adenocarcinoma (EAC) has risen 10-fold over the past half century and continues to have a dismal prognosis. Known risk factors for EAC do not adequately explain these incidence trends; the rise in EAC cases began a decade before increases in the prevalence of both gastro-esophageal reflux disease and obesity. Over the past 50+ years, dramatic changes in the bacterial composition (or microbiome) of the upper gastrointestinal tract have also occurred. While prior work has shown correlations between the microbiome, BE, and EAC, there is a critical knowledge gap on mechanisms by which bacteria interact with the esophagus and potentially promote cancer. The investigators hypothesize that increased levels of the certain bile acids in gastroesophageal reflux fluid cause changes that lead to increased interaction between bacteria and the esophagus, which may promote the development of esophageal adenocarcinoma (EAC). The investigators will carry out a case-control study of patients with and without BE, dysplasia, or EAC. The investigators will focus on deoxycholic acid in gastro-esophageal refluxate and its association with Notch signaling in tissue and bacterial composition. The microbiome represents a novel and potentially modifiable risk factor for the development of BE and EAC. Elucidation of microbiome features and mechanisms that promote the development of EAC is a critical step that will lead to subsequent trials of antibiotics, probiotics, and other interventions targeted to altering the microbiome, with the goal of lowering the risk of this highly lethal malignancy.