biostudies-literatureTian XNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)1001https://www.ebi.ac.uk/biostudies/studies/S-EPMC9701230biostudies-literatureUnknown13(11)Biliary atresia (BA) is a cholestatic liver disease in neonates with devastating obstructive intrahepatic and extrahepatic biliary ducts. Owing to the lack of an early diagnostic marker and limited understanding of its pathogenesis, BA often leads to death within 2 years. Therefore, this study aimed to develop early diagnostic methods and investigate the underlying pathogenesis of liver injury in BA using metabolomics. Metabolomics and organoid combined energy metabolism analysis was used to obtain new insights into BA diagnosis and pathobiology using patient samples, mice liver organoids, and a zebrafish model. Metabolomics revealed that D-2-hydroxyglutarate (D-2-HG) levels were significantly elevated in the plasma and liver of patients with BA and closely correlated with liver injuries aCell death & diseaseMetabolic regulation of cholestatic liver injury by D-2-hydroxyglutarate with the modulation of hepatic microenvironment and the mammalian target of rapamycin signaling.PMC970123082270537, 81974058Tian XLu YXiao YWu BDu JWang YChen SCai WfalseMetabolic regulation of cholestatic liver injury by D-2-hydroxyglutarate with the modulation of hepatic microenvironment and the mammalian target of rapamycin signaling.Biliary atresia (BA) is a cholestatic liver disease in neonates with devastating obstructive intrahepatic and extrahepatic biliary ducts. Owing to the lack of an early diagnostic marker and limited understanding of its pathogenesis, BA often leads to death within 2 years. Therefore, this study aimed to develop early diagnostic methods and investigate the underlying pathogenesis of liver injury in BA using metabolomics. Metabolomics and organoid combined energy metabolism analysis was used to obtain new insights into BA diagnosis and pathobiology using patient samples, mice liver organoids, and a zebrafish model. Metabolomics revealed that D-2-hydroxyglutarate (D-2-HG) levels were significantly elevated in the plasma and liver of patients with BA and closely correlated with liver injuries a2022-01-01T00:00:00Z2022 Nov2025-05-31T22:53:02.08Z2024-11-10T08:08:41.063ZS-EPMC97012303643586010.1038/s41419-022-05450-z