title: Serum metabolome and lipidome changes in adult patients with primary dengue infection.
abstract: BACKGROUND
  Dengue virus (DENV) is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF) is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.
  
  
  RESULTS
  Systems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44) across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.
  
  
  CONCLUSIONS
  DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive or prolonged inflammation. This study is the first example of how an omic- approach can divulge the extensive, concurrent, and dynamic host responses elicited by DENV and offers plausible physiological insights to why DF is self limiting.
authors: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology, Singapore.
authors: Liang
authors: L
authors: Cui
authors: Yie Hou
authors: YH
authors: Lee
authors: Yadunanda
authors: Y
authors: Kumar
authors: Fengguo
authors: F
authors: Xu
authors: Kun
authors: K
authors: Lu
authors: Eng Eong
authors: EE
authors: Ooi
authors: Steven R
authors: SR
authors: Tannenbaum
authors: Choon Nam
authors: CN
authors: Ong
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D003715:Dengue / Q000473:pathology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008137:Longitudinal Studies; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D044967:Serum / Q000737:chemistry*
chemical_list: D008055:Lipids
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