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J Proteome Res. 2015 Jun 5;14(6):2569-74. doi: 10.1021/acs.jproteome.5b00125. Epub 2015 Apr 27.

Metabonomics reveals metabolite changes in biliary atresia infants.

Author information

1
†Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), 1665 Kongjiang Road, Shanghai 200092, China.
2
‡Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai 200092, China.
3
§Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, 600 Yishan Road, Shanghai 200230, China.
4
∥University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, Hawaii 96813, United States.
5
⊥Department of Infection and Gastroenterology, Shanghai Children's Hospital, SJTU School of Medicine, 1400 West Beijing Road, Shanghai 200040, China.

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.

KEYWORDS:

amino acid; biliary atresia; metabonomics; neonatal hepatitis syndrome

PMID:
25899098
PMCID:
PMC6088235
DOI:
10.1021/acs.jproteome.5b00125
[Indexed for MEDLINE]
Free PMC Article

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