Metabolic profiling of an Echinostoma caproni infection in the mouse for biomarker discovery.
Author(s)
Type
Journal Article
Abstract
Background
Metabolic 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 Findings
Twelve 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/Significance
The 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.
Metabolic 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 Findings
Twelve 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/Significance
The 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.
Date Issued
2008-07-02
Date Acceptance
2008-05-21
Citation
PLoS Neglected Tropical Diseases, 2008, 2 (7), pp.1-15
ISSN
1935-2727
Publisher
Public Library of Science
Start Page
1
End Page
15
Journal / Book Title
PLoS Neglected Tropical Diseases
Volume
2
Issue
7
Copyright Statement
© 2008 Saric et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000254
Subjects
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Parasitology
Tropical Medicine
MAGNETIC-RESONANCE-SPECTROSCOPY
HUMAN BLOOD-PLASMA
CHAIN FATTY-ACIDS
CLOSTRIDIUM-AMINOVALERICUM
NEUTRAL LIPIDS
P-CRESOL
DISEASE
MICE
IDENTIFICATION
RATS
Animals
Biomarkers
Disease Models, Animal
Echinostoma
Echinostomiasis
Feces
Female
Humans
Metabolome
Mice
Mice, Inbred Strains
Plasma
Urine
Plasma
Urine
Feces
Animals
Mice, Inbred Strains
Humans
Mice
Echinostoma
Echinostomiasis
Disease Models, Animal
Female
Metabolome
Biomarkers
06 Biological Sciences
11 Medical and Health Sciences
Tropical Medicine
Publication Status
Published
Date Publish Online
2008-07-02