Esophageal Reflux Barrier Might be More than Just An Anatomical Definition: A Systematic Literature Review

Gastroesophageal reflux disease (GERD) is a common condition that affects millions of people worldwide. It can be stated that a defective esophageal reflux barrier (ERB) is the primary cause that can lead to these disease entities. The goal of this systematic review was to summarize and investigate the current literature regarding the functional and molecular aspects of the ERB in humans and the influence of anti-reflux surgery (ARS) on its improvement.

Pubmed, Embase, MEDLINE, and the Cochrane Library were searched from the earliest available date of each database through April 12, 2026. Outcome measurements of interest were changes in the molecular and cellular components of the ERB, as well as improvement in GERD symptoms measured objectively or subjectively.

The primary literature search produced 110 results, including six duplicates. After screening on title and abstract, 15 studies were found possibly relevant and underwent full-text critical appraisal, resulting in 14 exclusions. Only the study by Ergun et al. fulfilled the inclusion criteria and was therefore included in this systematic review. This study showed significant improvements after ARS in mucosal integrity, mucosal permeability, and mRNA gene expression of the following molecules: E-cadherin, occludin, claudin 1, claudin 4, zonula occludens-1 and zonula occludens-2.

ARS is responsible for many anatomical and physiological mechanisms, many of which are not yet fully understood. ARS may have positive effects on the mucosal and functional esophageal reflux barrier; however, further prospective studies need to further elucidate this.