Exploring the Mechanisms of Gastroesophageal Reflux Disease Based on the Brain-Gut Axis Theory

Gastroesophageal reflux disease (GERD) is a common clinical digestive disorder with a complex pathological mechanism. Traditional understanding of its mechanisms primarily focuses on factors such as lower esophageal sphincter dysfunction, impaired esophageal clearance, delayed gastric emptying, and abnormal gastric acid secretion. In recent years, the introduction of the brain-gut axis (BGA) theory has provided a new perspective for the systematic understanding of GERD's pathogenesis. However, there remains a significant lack of understanding regarding the specific mechanisms of BGA in GERD, particularly in terms of the interactions between the nervous, endocrine, and immune systems, and how they influence the symptoms and progression of gastroesophageal reflux. This paper aims to review the abnormal mechanisms of the nervous, endocrine, and immune systems in GERD based on the BGA theory, clarify the relationships between these systems in the development of GERD, and explore the current gaps in knowledge and future research directions. Studies have shown that GERD patients often present with neurological abnormalities such as central nervous system hypersensitivity, autonomic nervous imbalance, and enteric nervous system remodeling. Additionally, activation of the HPA axis and prolonged elevation of cortisol exacerbate esophageal injury, while local and systemic immune inflammation further induces visceral hypersensitivity, creating a stress-induced "neuroimmune loop". Based on the BGA mechanism, future individualized treatments for GERD, which integrate the regulation of central nervous function, endocrine levels, and the immune microenvironment, may provide new strategies and clinical interventions, leading to breakthroughs in relevant therapies.