UNDERSTANDING THE MECHANISMS UNDERLYING GASTROESOPHAGEAL REFLUX DISEASE (GERD) DEVELOPMENT: A SYSTEMATIC REVIEW

Abstract

Background: Gastroesophageal reflux disease (GERD) is a chronic condition with increasing global prevalence. Its pathogenesis is multifactorial, involving not just gastric acid, but also esophageal motility disorders, anatomical defects, inflammation, sensory hypersensitivity, and microbiota alterations.

Objective: To systematically review and synthesize empirical findings related to the mechanistic pathways underlying GERD development in adult populations.

Methods: This systematic review followed PRISMA 2020 guidelines. A structured search was conducted across PubMed, Web of Science, Scopus, Embase, and Google Scholar for studies published from 2010 to 2025. Inclusion criteria encompassed original human studies exploring GERD pathophysiology involving motility, inflammation, bile/pepsin reflux, hormonal dysregulation, genetics, and microbiota. Data extraction and quality appraisal were independently performed.

Results: Fifteen high- and moderate-quality studies were included. LES dysfunction and TLESRs were frequently reported (Kim et al., 2023), while inflammatory cytokines such as TNF-α and IL-6 (Zhou et al., 2023; Wei et al., 2024) emerged as critical markers of mucosal injury. Bile reflux, sensory hypersensitivity, microbiota changes, obesity, and surgical anatomy alterations further shaped GERD development.

Conclusion: GERD is a heterogeneous disease, with multiple overlapping pathophysiological mechanisms. These insights highlight the need for personalized diagnostic and therapeutic approaches extending beyond acid suppression.