The Potential Role of Helicobacter pylori-Related Mast Cell Activation in the Progression from Gastroesophageal Reflux to Barrett's Esophagus and Esophageal Adenocarcinoma

Abstract

Helicobacter pylori (Hp), a widespread gastric pathogen, has long been studied for its role in upper gastrointestinal disorders. While its involvement in gastritis, peptic ulcer disease, and gastric cancer is well established, its impact on esophageal diseases remains an area of ongoing investigation. Nevertheless, some data indicate that Hp may be involved in the pathogenesis of gastroesophageal reflux disease-Barrett's esophagus-esophageal adenocarcinoma sequence. Similarly, the Hp-related mast cell activation-an essential immunological event-may also play a crucial role in the progression from gastroesophageal reflux disease to Barrett's esophagus and esophageal adenocarcinoma. The underlying mechanisms include immune modulation, cytokine cascades, and microbial interactions that collectively shape the esophageal microenvironment. This review provides an in-depth analysis of these pathways, highlighting the potential role of Hp-induced, mast cell-driven inflammation in esophageal disease progression and discussing emerging therapeutic strategies.

Keywords: Barrett’s esophagus; Helicobacter pylori; esophageal adenocarcinoma; gastroesophageal reflux disease; mast cells; metabolic syndrome.

Figure 1

Role of Helicobacter pylori (Hp) and metabolic syndrome (MetS)-associated activated mast cells in the progression of gastroesophageal reflux disease (GERD) to Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). CCL2, chemokine ligand 2; CagA, cytotoxin-associated gene A; EMT, epithelial-mesenchymal transition; FGF, fibroblast growth factor; GPR, g-protein receptor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; LPS, lipopolysaccharides; LES, lower esophageal sphincter; MMPs, matrix metalloproteinases; NAP, neutrophil-activating protein;PD-1, programmed death-ligand 1; PGs, prostaglandins; ROS, reactive oxygen metabolites; Tregs, regulatory T cells; Th, T-helper; TLR, toll-like receptor; TGF, transforming growth factor; TNF, tumor necrosis. (Created in BioRender. Kazakos, E.I. (2025) https://BioRender.com/fxncune, accessed on 3 July 2025).