Gastroesophageal reflux disease in patients with obesity: motor, immunometabolic and mucosal barrier mechanisms of progression. Part 2

Abstract

Gastroesophageal reflux disease (GERD) in patients with obesity develops not only due to increased intra-abdominal pressure but also through a complex interaction of motor, immunometabolic, hormonal and mucosal barrier disturbances. The aim of this review was to summarize current evidence on the mechanisms of GERD progression in obese patients, focusing on mechanical and motor factors, cytokine and hormonal imbalance, impairment of the esophageal mucosal barrier and cellular targets in different metabolic obesity phenotypes. The article was prepared as a literature review with elements of a systematic search in PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect and Cochrane Library. Clinical, cohort, instrumental, review and meta-analytic studies evaluating the relationships between obesity, metabolic dysfunction, esophageal motility, acid exposure, cytokines, adipokines, hormonal regulators and structural integrity of the esophageal mucosa were included. Current evidence indicates that in metabolically unhealthy obesity and metabolically unhealthy normal weight, the leading mechanisms include insulin resistance, leptin and adiponectin imbalance, activation of tumor necrosis factor α, interleukins and 1β, reduced anti-inflammatory regulation, impaired lower esophageal sphincter tone, increased transient lower esophageal sphincter relaxations, reduced esophageal clearance and disruption of epithelial tight junctions. Visceral adipose tissue acts as an active endocrine and immunometabolic organ linking systemic inflammation with local mucosal injury. These findings support a pathogenetically oriented approach to diagnosis, prediction of treatment refractoriness and prevention of GERD complications in obese patients.