Submitted on May 27, 2005
Revised on October 12, 2005
Accepted on October 18, 2005
Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers
Ina Bergheim, Simone Harsch, Oliver Mueller, Silke Schimmel, Peter Fritz, and Eduard F. Stange
Abteilung Innere Medizin 1 , Robert-Bosch-Krankenhaus , Stuttgart D-70376
Corresponding Author: eduard.stange{at}rbk.de
While a cholesterol supersaturation of gallbladder bile has been identified as the underlying pathophysiologic defect the molecular pathomechnism of gallstone formation in humans remains poorly understood. A deficiency of the apical sodium-dependent bile acid transporter (ASBT) and ileal lipid binding protein (ILBP) in the small intestine may result in bile acid loss into the colon and might promote gallstone formation by reducing the bile acid pool and increasing the amount of hydrophobic bile salts. To test this hypothesis protein levels and mRNA expression of ASBT and ILBP were assessed in ileal mucosa biopsies of female gallstone carriers and controls. Neither ASBT nor ILBP levels differed significantly between gallstone carriers and controls. However, when sub-grouping study participants by body-weight, ASBT and ILBP protein were 48% and 67% lower in normal weight gallstone carriers than in controls (p<0.05); similar differences were found for mRNA expression levels. The loss of bile transporters in female normal weight gallstone carriers was coupled with a reduction of protein levels of hepatic nuclear factor 1 
(HNF1) and farnesoid X-receptor (FXR). In conclusion, in normal weight female gallstone carriers the decreased expression of ileal bile acid transporters may form a molecular basis for gallstone formation.
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