Cholesterol supersaturation of gallbladder bile has been identified as the underlying pathophysiologic defect of gallstone formation.
However, the molecular pathomechnism of gallstone formation in humans remains poorly understood.
A deficiency of the apical sodium-dependent bile acid transporter
in the small intestine may result in bile acid loss into the colon.
In addition, a deficiency of ileal lipid binding protein in the small intestine may result in bile acid loss into the colon.
This might promote gallstone formation by reducing the bile acid pool and increasing the amount of hydrophobic bile salts.
Professor Eduard Stange and colleagues from Germany tested this hypothesis.
Protein levels and mRNA expression of apical sodium-dependent bile acid transporter and ileal lipid binding protein were assessed.
| Apical sodium-dependent bile acid transporter was 48% lower in normal weight gallstone carriers |
| Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology |
The researchers assessed these markers in ileal mucosa biopsies of female gallstone carriers and controls.
The researchers found that apical sodium-dependent bile acid transporters did not differ significantly between gallstone carriers and controls.
Ileal lipid binding protein levels also did not differ between gallstone carriers and controls.
However, when sub-grouping study participants by body-weight, apical sodium-dependent bile acid transporter was 48% lower in normal weight gallstone carriers.
The researchers noted that ileal lipid binding protein was 67% lower in normal weight gallstone carriers than in controls.
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 alpha.
The loss of bile transporter in these patients was also coupled with a reduction of farnesoid X-receptor.
Professor Stange commented, “In normal weight female gallstone carriers the decreased expression of ileal bile acid transporters may form a molecular basis for gallstone formation.”