Secondary bile acids and the biliary epithelia: The good and the bad

Abstract

The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine. Nowadays several researches demonstrated an important role of biliary epithelia (i.e. cholangiocytes) in bile formation. The study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases, such as primary biliary cholangitis or primary sclerosing cholangitis. Bile acids (BAs), produced by the liver, are the most represented organic molecules in bile. The physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling molecules. In this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary (deriving by bacterial manipulation of primary molecules) ones. This class of BAs is demonstrated to have relevant biological effects, ranging from toxic to therapeutic ones. In this family ursodeoxycholic and lithocholic acid present the most interesting features. The molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic damage. These findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders.

Keywords: Cholangiocytes, Biliary secretion, Cholestasis, Bile acids, Secondary bile acids, Ursodeoxycholic acid, Lithocholic acid

Core Tip: The biliary epithelia present important physiologic activities that are of interest with regard to chronic cholestatic liver diseases. Secondary bile acids (BAs) are derived by bacterial manipulation of the primary BAs produced by the liver. This review summarizes the most important recent findings with regard to secondary BAs interaction with biliary epithelia.