The esophageal microbiome–helicobacter pylori axis in gastroesophageal reflux disease and its therapeutic implication

Gastroesophageal reflux disease (GERD) is a chronic gastrointestinal disorder caused by the reflux of gastric contents into the esophagus, leading to symptoms such as heartburn, regurgitation, and dysphagia. Persistent reflux can result in complications including reflux esophagitis (RE), non-erosive reflux disease (NERD), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). Besides gastric acid exposure and lower esophageal sphincter dysfunction, emerging evidence suggests that alterations in the esophageal microbiome play an important role in GERD pathogenesis and progression. This review summarizes the clinical spectrum, inflammatory mechanisms, and microbial alterations associated with GERD, with particular focus on the role of Helicobacter pylori and esophageal dysbiosis. Differences between healthy and diseased esophageal microbiota, along with the influence of factors such as diet, obesity, smoking, antibiotics, proton pump inhibitors, and probiotics, are discussed. The review also highlights the involvement of inflammatory pathways, including Toll-like receptor and NF-κB signaling, in reflux-associated mucosal injury. Finally, potential therapeutic strategies targeting microbiome modulation, including probiotics, prebiotics, bacteriocins, and anti-inflammatory approaches, are explored. Understanding the interaction between the esophageal microbiome and GERD may provide new insights for improved diagnosis, prevention, and treatment of esophageal diseases. Graphical abstract