Lipidomic characterization of bile and serum reveals an altered lipid landscape in end-stage primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of bile ducts, yet its metabolic underpinnings remain poorly defined. Previous lipidomic studies in PSC have focused on either bile or serum, but a systematic comparison across bile, peripheral blood serum and portal vein serum has not been undertaken. We aimed to characterize lipid alterations in these biofluids in patients with advanced PSC to better understand associated metabolic changes. Bile and serum (peripheral and portal vein) samples were collected during transplantation from patients with end-stage PSC (n = 7 and bile; n = 8 for serum) and controls (n = 16 for bile; n = 13 for serum). High-resolution untargeted lipidomics using liquid chromatography-tandem mass spectrometry was performed to investigate biliary and serum lipid alterations in end-stage PSC. More pronounced lipidomic alterations were observed in bile as compared to serum from peripheral or portal vein, with several lipid subclasses showing significant changes in end-stage PSC. The most notable differences included elevated levels of biliary dihexosylceramides, lysophosphatidic acids and triacylglycerol in PSC. Serum from peripheral and portal vein generally exhibited similar trends, with a decrease in lysophospholipids. These findings expand the current understanding of lipid dysregulation in advanced PSC and highlight the distinct metabolic alterations in bile and serum compartments.