Chemometric analysis of biofluids from mice experimentally infected with Schistosoma mansoni

Li, J. V. and Saric, J. and Wang, Y. and Keiser, J. and Utzinger, J. and Holmes, E.. (2011) Chemometric analysis of biofluids from mice experimentally infected with Schistosoma mansoni. Parasites and Vectors, 4 (179).

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Official URL: http://edoc.unibas.ch/dok/A6002136

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BACKGROUND: The urinary metabolic fingerprint of a patent Schistosoma mansoni infection in the mouse has been characterized using spectroscopic methods. However, the temporal dynamics of metabolic alterations have not been studied at the systems level. Here, we investigated the systems metabolic changes in the mouse upon S. mansoni infection by modeling the sequence of metabolic events in urine, plasma and faecal water.
METHODS: Ten female NMRI mice, aged 5 weeks, were infected with 80 S. mansoni cercariae each. Ten age- and sex-matched mice remained uninfected and served as a control group. Urine, plasma and faecal samples were collected 1 day before, and on eight time points until day 73 post-infection. Biofluid samples were subjected to 1H nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses.
RESULTS: Differences between S. mansoni-infected and uninfected control mice were found from day 41 onwards. One of the key metabolic signatures in urine and faecal extracts was an alteration in several gut bacteria-related metabolites, whereas the plasma reflected S. mansoni infection by changes in metabolites related to energy homeostasis, such as relatively higher levels of lipids and decreased levels of glucose. We identified 12 urinary biomarkers of S. mansoni infection, among which hippurate, phenylacetylglycine (PAG) and 2-oxoadipate were particularly robust with regard to disease progression. Thirteen plasma metabolites were found to differentiate infected from control mice, with the lipid components, D-3-hydroxybutyrate and glycerophosphorylcholine showing greatest consistency. Faecal extracts were highly variable in chemical composition and therefore only five metabolites were found discriminatory of infected mice, of which 5-aminovalerate was the most stable and showed a positive correlation with urinary PAG.
CONCLUSIONS: The composite metabolic signature of S. mansoni in the mouse derived from perturbations in urina faecal and plasma composition showed a coherent response in altered energy metabolism and in gut microbial activity. Our findings provide new mechanistic insight into host-parasite interactions across different compartments and identified a set of temporally robust biomarkers of S. mansoni infection, which might assist in derivation of diagnostic assays or metrics for monitoring therapeutic response
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Helminth Drug Development (Keiser)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Health Impact Assessment (Utzinger)
UniBasel Contributors:Utzinger, Jürg and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Nov 2016 14:55
Deposited On:08 Nov 2012 16:11

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