title: Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces.
abstract: 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 gastro-oesophageal reflux disease (GORD), who are taking proton pump inhibitors (PPIs), 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 assess 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 effects of different solutions containing bile acids, applied to the mucosal side, on transepithelial electrical resistance (R(T)) and permeability to fluorescein. The diameter of intercellular spaces was assessed by using transmission electron microscopy.
  
  
  RESULTS
  Incubation of oesophageal mucosa with acidic solutions (pH 2.0) containing a range of bile acids (0.5-5 mmol/l) markedly decreased R(T) and increased mucosal permeability. Weakly acidic solutions (pH 5.0), and to some extent neutral solutions (pH 7.4), containing some bile acids also decreased R(T) and increased permeability, although the effects were much less marked and in some combinations no effect was seen. Exposure to bile acids provoked DIS in acid and weakly acidic conditions but not in neutral (pH 7.4) solutions.
  
  
  CONCLUSIONS
  Experimental short exposure of the oesophageal mucosa to solutions with a bile acid concentration and acidity similar to that observed in the gastric contents of patients with NERD or ERD, and who are taking PPIs, may impair oesophageal mucosal integrity and even induce dilated intercellular spaces. Such a situation could, theoretically, underlie the occurrence and/or persistence of symptoms in these patients.
authors.affiliation: Center for Gastroenterological Research, Catholic University Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Farré
authors.forename: H
authors.initials: H
authors.lastname: van Malenstein
authors.forename: R
authors.initials: R
authors.lastname: De Vos
authors.forename: K
authors.initials: K
authors.lastname: Geboes
authors.forename: I
authors.initials: I
authors.lastname: Depoortere
authors.forename: P
authors.initials: P
authors.lastname: Vanden Berghe
authors.forename: F
authors.initials: F
authors.lastname: Fornari
authors.forename: K
authors.initials: K
authors.lastname: Blondeau
authors.forename: V
authors.initials: V
authors.lastname: Mertens
authors.forename: J
authors.initials: J
authors.lastname: Tack
authors.forename: D
authors.initials: D
authors.lastname: Sifrim
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D050782:Esophageal pH Monitoring; D005110:Extracellular Space / Q000502:physiology; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects*; D011817:Rabbits
chemical_list: D001647:Bile Acids and Salts