Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking

The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus ( BO ) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium ( HET ‐1A) and BO ( QH ) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α 3 , α 4, α 5 , α 6 and α ν ). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease ( GORD ) and in patient tissue microarrays. The bile acid deoxycholic acid ( DCA ) specifically reduced adhesion of HET ‐1A cells to vitronectin and reduced cell‐surface expression of integrin‐α ν via effects on endocytic recycling processes. Increased expression of integrin‐α v was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin‐α ν was observed in QH BO cells compared to HET ‐1A cells. QH cells were resistant to DCA ‐mediated loss of adhesion and reduction in cell‐surface expression of integrin‐α ν . We demonstrated that a specific component of the gastric refluxate, DCA , affects the epithelial barrier through modulation of integrin α ν expression, providing a novel mechanism for bile acid‐mediated erosion of oesophageal squamous epithelium and promotion of BO . Strategies aimed at preventing bile acid‐mediated erosion should be considered in the clinical management of patients with GORD .