Pathophysiology of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder whose pathophysiology involves multiple anatomical, functional, sensory, and neuropsychological factors. This article provides a critical and updated review of the main mechanisms involved in GERD development. It highlights transient lower esophageal sphincter relaxations as the predominant reflux mechanism in patients without hiatal hernia, and also addresses anatomical disruption of the esophagogastric junction, particularly hiatal hernia, as a major contributor to antireflux barrier dysfunction. Esophageal acid clearance impairment and loss of mucosal integrity are discussed as additional contributors to prolonged reflux exposure and esophageal hypersensitivity. Likewise, the interactions of the gut-brain axis are explored, especially in patients with refractory symptoms, highlighting the role of anxiety, depression, and hypervigilance. Furthermore, emerging evidence regarding the esophageal microbiota and its contribution to chronic inflammation and Barrett’s esophagus is reviewed. This integrative review incorporates recent data from physiological, manometric, and molecular studies, offering a multifactorial and dynamic view of GERD pathophysiology. A thorough understanding of these mechanisms is essential to develop individualized clinical approaches and novel therapeutic strategies.