Intestinal FXR antagonists such as ursodeoxycholic acid (UDCA), glycine-β-muricholic acid (GβMCA), and glycoursodeoxycholic acid (GUDCA) were suggested in mouse models to be of potential value for the treatment of primary biliary cirrhosis (PBC), NAFLD, obesity and atherosclerosis through regulating the FXR/SMPD3 axis and reducing the biosynthesis of intestine-derived ceramides18–22. This evidence concerns the gene SMPD3 and primary biliary cholangitis.