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Panorganismal metabolic response modelling of an experimental Echinostoma caproni infection in the mouse

Saric, J. and Li, J. V. and Wang, Y. and Keiser, J. and Veselkov, K. A. and Dirnhofer, S. and Yap, I. K. and Nicholson, J. K. and Holmes, E. and Utzinger, J.. (2009) Panorganismal metabolic response modelling of an experimental Echinostoma caproni infection in the mouse. Journal of Proteome Research, Vol. 8, H. 8. pp. 3899-3911.

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Official URL: http://edoc.unibas.ch/dok/A5843283

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Abstract

Metabolic profiling of host tissues and biofluids during parasitic infections can reveal new biomarker information and aid the elucidation of mechanisms of disease. The multicompartmental metabolic effects of an experimental Echinostoma caproni infection have been characterized in 12 outbred female mice infected orally with 30 E. caproni metacercariae each, using a further 12 uninfected animals as a control group. Mice were killed 36 days postinfection and brain, intestine (colon, ileum, jejeunum), kidney, liver, and spleen were removed. Metabolic profiles of tissue samples were measured using high-resolution magic angle spinning 1H NMR spectroscopy and biofluids measured by applying conventional 1H NMR spectroscopy. Spectral data were analyzed via principal component analysis (PCA), partial least squares (PLS)-derived methods and hierarchical projection analyses (H-PLS). Infection-induced metabolic changes in the tissues were correlated with altered metabolite concentrations in the biofluids (urine, plasma, fecal water) using hierarchical modeling and correlation analyses. Metabolic descriptors of infection were identified in liver, renal cortex, intestinal tissues but not in spleen, brain or renal medulla. The main physiological change observed in the mouse was malabsorption in the small intestine, which was evidenced by decreased levels of various amino acids in the ileum, e.g., alanine, taurine, glutamine, and branched chain amino acids. Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon. Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments. In conclusion, an E. caproni infection not only results in direct (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore describes the panorganismal metabolic response of the infection
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 > Helminth Drug Development (Keiser)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Eco System Health Sciences > Health Impact Assessment (Utzinger)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
UniBasel Contributors:Dirnhofer, Stephan and Keiser, Jennifer and Utzinger, Jürg
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Chemical Society
ISSN:1535-3893
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:42
Deposited On:14 Sep 2012 06:42

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