AUTHOR=Li Chong , Cao Xiwen , Wang Hongxia 

TITLE=Pathogenesis of pepsin-induced gastroesophageal reflux disease with advanced diagnostic tools and therapeutic implications

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1516335

DOI=10.3389/fmed.2025.1516335

ISSN=2296-858X

ABSTRACT=Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder that significantly affects populations in both developing and developed countries. Due to both intrinsic pathology and extrinsic risk factors, the incidence of GERD has risen substantially in recent decades. This disorder results from an imbalance between the esophagus’s defensive mechanisms and the harmful effects of the refluxate. The pepsin, an enzyme secreted exclusively by the stomach, plays a critical role in the pathogenesis of GERD due to its invasiveness effects in acidic environments. By thoroughly understanding the pathogenesis of pepsin-induced GERD, we could better address its diagnostic and therapeutic potential in clinical practice. Although current diagnostic tools are widely used, they have several limitations. As a result, researchers have increasingly focused on the salivary pepsin test, a novel diagnostic method that utilizes the specific pathological mechanisms of pepsin. To overcome the drawbacks of the currently used salivary pepsin test, fluorescence response detection has been integrated with other technologies. Beyond its diagnostic significance, pepsin in saliva may also serve as a target for GERD management in innovative clinical trials. In this review, we summarize the latest advancements in the diagnosis and management of GERD to improve patient outcomes.