Farré et al. 1 SHORT EXPOSURE OF OESOPHAGEAL MUCOSA TO BILE ACIDS, BOTH IN ACIDIC AND WEAKLY ACIDIC CONDITIONS, CAN IMPAIR MUCOSAL INTEGRITY AND PROVOKE DILATED INTERCELLULAR SPACES Short running head: bile acids and oesophageal mucosa permeability in ra

BACKGROUND: Severe duodeno-gastro-oesophageal reflux (DGOR) is a risk factor for oesophagitis and Barrett’s oesophagus. Patients with non-erosive reflux disease (NERD) have a slight increase in DGOR. Patients with GORD, “on ” PPI, still have reflux but of weakly acidic pH and persistence of bile. In these two groups of patients, heartburn might be due to increased oesophageal mucosal permeability and dilated intercellular spaces (DIS). We aimed to asses whether experimental short exposure of the oesophageal mucosa to bile acids, in low concentrations (at acidic, weakly acidic and neutral conditions) can increase mucosal permeability and provoke DIS. METHODS: Rabbit oesophageal mucosa was studied in diffusion and Ussing chambers. We assessed the effect of different solutions containing bile acids, applied in the mucosal side, on transepithelial resistance (RT) and permeability to fluorescein. Diameter of intercellular spaces was assessed with transmission electron microscopy. RESULTS: Incubation of oesophageal mucosa with acidic solutions (pH 2.0) containing a range of bile acids (0.5mM-5mM) markedly decreased RT and increased mucosa permeability. Weakl