| Summary: | <p>Abstract</p> <p>Background</p> <p>The urinary metabolic fingerprint of a patent <it>Schistosoma mansoni </it>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 <it>S. mansoni </it>infection by modeling the sequence of metabolic events in urine, plasma and faecal water.</p> <p>Methods</p> <p>Ten female NMRI mice, aged 5 weeks, were infected with 80 <it>S. mansoni </it>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 <sup>1</sup>H nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses.</p> <p>Results</p> <p>Differences between <it>S. mansoni</it>-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 <it>S. mansoni </it>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 <it>S. mansoni </it>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.</p> <p>Conclusions</p> <p>The composite metabolic signature of <it>S. mansoni </it>in the mouse derived from perturbations in urinary, 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 <it>S. mansoni </it>infection, which might assist in derivation of diagnostic assays or metrics for monitoring therapeutic response.</p>
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