Research Article: Metabolic Profiling of an Echinostoma caproni Infection in the Mouse for Biomarker Discovery

Date Published: July 2, 2008

Publisher: Public Library of Science

Author(s): Jasmina Saric, Jia V. Li, Yulan Wang, Jennifer Keiser, Jake G. Bundy, Elaine Holmes, Jürg Utzinger, David Blair

Abstract: BackgroundMetabolic profiling holds promise with regard to deepening our understanding of infection biology and disease states. The objectives of our study were to assess the global metabolic responses to an Echinostoma caproni infection in the mouse, and to compare the biomarkers extracted from different biofluids (plasma, stool, and urine) in terms of characterizing acute and chronic stages of this intestinal fluke infection.Methodology/Principal FindingsTwelve female NMRI mice were infected with 30 E. caproni metacercariae each. Plasma, stool, and urine samples were collected at 7 time points up to day 33 post-infection. Samples were also obtained from non-infected control mice at the same time points and measured using 1H nuclear magnetic resonance (NMR) spectroscopy. Spectral data were subjected to multivariate statistical analyses. In plasma and urine, an altered metabolic profile was already evident 1 day post-infection, characterized by reduced levels of plasma choline, acetate, formate, and lactate, coupled with increased levels of plasma glucose, and relatively lower concentrations of urinary creatine. The main changes in the urine metabolic profile started at day 8 post-infection, characterized by increased relative concentrations of trimethylamine and phenylacetylglycine and lower levels of 2-ketoisocaproate and showed differentiation over the course of the infection.Conclusion/SignificanceThe current investigation is part of a broader NMR-based metabonomics profiling strategy and confirms the utility of this approach for biomarker discovery. In the case of E. caproni, a diagnosis based on all three biofluids would deliver the most comprehensive fingerprint of an infection. For practical purposes, however, future diagnosis might aim at a single biofluid, in which case urine would be chosen for further investigation, based on quantity of biomarkers, ease of sampling, and the degree of differentiation from the non-infected control group.

Partial Text: An estimated 40 million individuals are infected with food-borne trematodes and, in many parts of the world, the diseases caused by these infections are emerging [1]. Yet, food-borne trematodiases are so-called neglected tropical diseases [2]. An infection with food-borne trematodes is acquired by the consumption of the larval stage of the parasite, present in aquatic food products (e.g., freshwater fish, crustacean, and water plants). Adult flukes reside either in the intestine (e.g., Echinostoma spp.), the lung (e.g., Paragonimus spp.), or the liver (e.g., Clonorchis sinensis, Fasciola spp., Opisthorchis spp.) and can lead to various forms of pathology [2],[3].

1H NMR-based metabolic profiling of biofluids is an established method for deepening our understanding of host-parasite interactions and for investigating disease states in clinical studies [15],[19],[33]. Sample preparation and spectral acquisition of a biofluid takes little time, and often an overview of the metabolic state of the organism can be obtained by visual assessment of the spectra. Identification of biomarkers from different types of biofluids is similarly convenient, although stool samples need slightly more preparation time and require sonication and an additional centrifugation step, due to the high amount of sediments in the stool-buffer mixture [34].



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