Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces
Ricard Farre 1, Hannah van Malenstein 1, Rita de Vos 2, Karel Geboes 2, Inge Depoortere 3, Pieter Vanden Berghe 1, Fernando Fornari 1, Kathleen Blondeau 1, Veerle Mertens 1, Jan Tack 1 and Daniel Sifrim 1*
1 Center for Gastroenterological Research, KULeuven, Belgium
2 Department of Pathology, University Hospital Gasthuisberg, KULeuven, Belgium
3 Department of Pathology, University Center for Gastroenterological Research, KULeuven, Belgium
* To whom correspondence should be addressed. E-mail: daniel.sifrim{at}med.kuleuven.be.
Accepted 13 June 2008
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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, (in acidic, weakly acidic and weakly alkaline 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. Weakly acidic solutions (pH 5.0), and to some extent neutral solutions (pH 7.4), containing some bile acid also decreased RT and increased permeability though the effects were much less marked and in some combinations no effect was seen. Bile acids exposure 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 bile acids concentration and acidity, similar to that observed in gastric contents of NERD patients or ERD patients "on" PPI, may impair oesophageal mucosal integrity and even induce dilated intercellular spaces. Such situation could, theoretically, underlie the occurrence and/or persistence of symptoms in these patients.
