Nina Zhang, Véronique M P de Bruijn, Weijia Zheng, Wouter Bakker, Bennard van Ravenzwaay, Ivonne M C M Rietjens
Enterohepatic circulation of bile acids is a highly efficient process that is important for bile acid homeostasis. The aim of the present study was to characterize the impact of a series of antibiotics (lincomycin, streptomycin, vancomycin and tobramycin) on the intestinal reuptake of conjugated bile acids (TCA, TCDCA, GCA and GCDCA) using a Caco-2 in vitro transwell model system. The results obtained demonstrate that both pre-exposure and co-exposure of the cells to an antibiotic and the bile acids, affected bile acid transport, to an extent that depended on the antibiotic, its concentration and the type of conjugated bile acid tested. Tobramycin, at concentrations in line with dose levels at which this antibiotic induced effects on bile acid homeostasis in vivo, appeared able to inhibit bile acid transport after pre-exposure of the cells, likely resulting from an effect on the expression of bile acid transporters via its effects on protein synthesis at ribosome level. Upon co-exposure of the Caco-2 cells to an antibiotic and the bile acids, all four antibiotics appeared to significantly reduce the transport of especially the conjugated bile acids TCDCA and GCDCA with a potency that decreased in the order vancomycin > tobramycin = streptomycin > lincomycin. The effects observed illustrate the possibility of using a new approach methodology (NAM) to study effects on intestinal bile acid reuptake.
