title: Metabonomics reveals metabolite changes in biliary atresia infants.
abstract: Biliary atresia (BA) is a rare neonatal cholestatic disorder caused by obstruction of extra- and intra-hepatic bile ducts. If untreated, progressive liver cirrhosis will lead to death within 2 years. Early diagnosis and operation improve the outcome significantly. Infants with neonatal hepatitis syndrome (NHS) present similar symptoms, confounding the early diagnosis of BA. The lack of noninvasive diagnostic methods to differentiate BA from NHS greatly delays the surgery of BA infants, thus deteriorating the outcome. Here we performed a metabolomics study in plasma of BA, NHS, and healthy infants using gas chromatography-time-of-flight mass spectrometry. Scores plots of orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and healthy infants. Eighteen metabolites were found to be differentially expressed between BA and NHS, among which seven (l-glutamic acid, l-ornithine, l-isoleucine, l-lysine, l-valine, l-tryptophan, and l-serine) were amino acids. The altered amino acids were quantitatively verified using ultraperformance liquid chromatography-tandem mass spectrometry. Ingenuity pathway analysis revealed the network of "Cellular Function and Maintenance, Hepatic System Development and Function, Neurological Disease" was altered most significantly. This study suggests that plasma metabolic profiling has great potential in differentiating BA from NHS, and amino acid metabolism is significantly different between the two diseases.
authors.affiliation: †Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), 1665 Kongjiang Road, Shanghai 200092, China.|‡Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhou
authors.affiliation: §Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, 600 Yishan Road, Shanghai 200230, China.|∥University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, Hawaii 96813, United States.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: †Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: §Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, 600 Yishan Road, Shanghai 200230, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.affiliation: §Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, 600 Yishan Road, Shanghai 200230, China.
authors.forename: Jiajian
authors.initials: J
authors.lastname: Liu
authors.affiliation: ∥University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, Hawaii 96813, United States.
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.affiliation: ∥University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, Hawaii 96813, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ni
authors.affiliation: †Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: †Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Pan
authors.affiliation: ⊥Department of Infection and Gastroenterology, Shanghai Children's Hospital, SJTU School of Medicine, 1400 West Beijing Road, Shanghai 200040, China.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Che
authors.affiliation: ⊥Department of Infection and Gastroenterology, Shanghai Children's Hospital, SJTU School of Medicine, 1400 West Beijing Road, Shanghai 200040, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: ‡Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: ‡Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: ‡Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.affiliation: §Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, 600 Yishan Road, Shanghai 200230, China.|∥University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, Hawaii 96813, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: †Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), 1665 Kongjiang Road, Shanghai 200092, China.|‡Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D001656:Biliary Atresia / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D008297:Male; D055432:Metabolomics; D053719:Tandem Mass Spectrometry
keywords: amino acid; biliary atresia; metabonomics; neonatal hepatitis syndrome