Reduced ileal expression of organic solute transporter alpha and beta (OSTalpha -OSTbeta ) in non-obese gallstone disease.

Cholelithiasis is a multifactorial process and several mechanisms have been postulated. A decreased expression of the ileal apical sodium-dependent bile acid transporter (ASBT) and of the cytosolic ileal lipid binding protein (ILBP) was recently described in female non-obese patients. The role of the recently identified organic solute transporter (OSTa-OSTss) in gallstone pathogenesis remains still unclear. Therefore we performed analysis of OSTa-OSTss in gallstone patients, regarding body weight. Ileal mucosal biopsies were collected during routinely colonoscopy from female gallstone carriers (n=19) and controls (n=34). OSTa-OSTss mRNA expression was measured using the LightCycler sequence detection system; protein was analyzed by immunohistochemistry and Western blot. The mRNA expression of OSTa-OSTss was significantly (OSTa: 3.3-fold, p=0.006; OSTss: 2.6-fold, p=0.03) reduced in normal weight but not overweight gallstone carriers compared to controls. OSTa-OSTss protein levels also showed a reduction by 40-67%. The expression of OSTa-OSTss correlated positively with ASBT (r=0.65; 0.58, respectively), ILBP (r=0.77; 0.67), the farnesoid X receptor (FXR) (r=0.58; 0.50). Fibroblast growth factor-19 (FGF-19) showed a 2.8-fold (p=0.06) and liver receptor homolog-1 (LRH-1) a 2.0-fold reduction (p=0.04) in non-obese patients. In conclusion, an impaired function of all three ileal bile acid transporters may lead to low ileal bile acid reabsorption, an altered bile acid pool composition and therefore contribute to the formation of gallstones in non-obese.