Molecular and Functional Recovery of Esophageal Barrier Integrity After Laparoscopic Anti-reflux Surgery

• Published in: Digestive diseases and sciences Vol. 70; no. 8; pp. 2665 - 2673
• Main Authors: Ergun, Pelin, Kipcak, Sezgi, Gorgulu, Volkan, Doganavsargil, Basak, Bor, Serhat
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2025; Springer Nature B.V
• Subjects: Acids; Adult; Aged; Biochemistry; Biopsy; Body mass index; Cadherins - genetics; Cadherins - metabolism; Case-Control Studies; Drug use; Endoscopy; Esophageal Mucosa - metabolism; Esophageal Mucosa - pathology; Esophagus; Esophagus - metabolism; Esophagus - pathology; Esophagus - surgery; Female; Fundoplication - methods; Gastroenterology; Gastroesophageal reflux; Gastroesophageal Reflux - metabolism; Gastroesophageal Reflux - pathology; Gastroesophageal Reflux - surgery; Gene expression; Health care; Hepatology; Humans; Laboratories; Laparoscopy; Male; Medicine; Medicine & Public Health; Middle Aged; Occludin - genetics; Occludin - metabolism; Oncology; Original Article; Pathogenesis; Patients; Permeability; Recovery of Function; Surgery; Transplant Surgery; Treatment Outcome; Los Angeles California; United States > US; Netherlands; Ussing chamber; Tight junctions; Laparoscopic anti-reflux surgery; Dilated intercellular spaces; Gastroesophageal reflux disease
• ISSN: 0163-2116; 1573-2568; 1573-2568
• DOI: 10.1007/s10620-025-08951-x

Background Patients undergoing laparoscopic anti-reflux surgery (LARS) often experience improved quality of life and reduced gastroesophageal reflux disease (GERD) symptoms. This study aimed to assess the impact of LARS on epithelial remodeling and repair in the esophageal mucosa. Methods Upper gastrointestinal (GI) endoscopy was performed once on healthy controls (HC) and twice on GERD patients before and approximately 6 month after surgery, with esophageal biopsies collected. The expressions of E-cadherin (ECAD), Occludin ( OCLN ), Claudin 1 ( CLDN1 ), Claudin 4 ( CLDN4 ), Zonula Occludens -1 ( ZO-1 ), and ZO-2 were analyzed in the biopsies, and dilated intercellular spaces (DIS) were examined under light microscopy. Results The study included 22 GERD patients who were underwent for LARS, and 20 HCs. All patients had pathological reflux episodes. In the Post-LARS group, TEER increased significantly compared to Pre-LARS and HC ( p  < 0.05), while mucosal permeability decreased ( p  < 0.05). A significant negative correlation was found between TEER and permeability ( p  = 0.0002). DIS remained dilated in both Pre- and Post-LARS patients compared to HC ( p  < 0.05). Gene expression analysis revealed significant increases in ZO-1, OCLN , and ZO-2 Post-LARS ( p  < 0.05). Conclusion LARS improves mucosal integrity by enhancing TEER and reducing permeability in GERD patients, although DIS remains unchanged. The upregulation of tight junction genes such as ZO-1 and OCLN Post-LARS suggests that surgical intervention may support epithelial barrier restoration. DIS remains dilated after LARS; this might be reason that it is not an early marker in GERD pathogenesis. These findings enhance our understanding of GERD nature and may inform future target therapeutic strategies.