Abstract
Introduction
Manifestations of fatigue range from chronic fatigue up to a severe syndrome and myalgic encephalomyelitis. Fatigue grossly affects the functional status and quality of life of affected individuals, prompting the World Health Organization to recognize it as a chronic non-communicable condition.
Objectives
Here, we explore the potential of urinary metabolite information to complement clinical criteria of fatigue, providing an avenue towards an objective measure of fatigue in patients presenting with the full spectrum of fatigue levels.
Methods
The experimental group consisted of 578 chronic fatigue female patients. The measurement design was composed of (1) existing clinical fatigue scales, (2) a hepatic detoxification challenge test, and (3) untargeted proton nuclear magnetic resonance (1H-NMR) procedure to generate metabolomics data. Data analysed via an in-house Matlab script that combines functions from a Statistics and a PLS Toolbox.
Results
Multivariate analysis of the original 459 profiled 1H-NMR bins for the low (control) and high (patient) fatigue groups indicated complete separation following the detoxification experimental challenge. Important bins identified from the 1H-NMR spectra provided quantitative metabolite information on the detoxification challenge for the fatigue groups.
Conclusions
Untargeted 1H-NMR metabolomics proved its applicability as a global profiling tool to reveal the impact of toxicological interventions in chronic fatigue patients. No clear potential biomarker emerged from this study, but the quantitative profile of the phase II biotransformation products provide a practical visible effect directing to up-regulation of crucial phase II enzyme systems in the high fatigue group in response to a high xenobiotic-load.
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Funding
Research funding for the analytical and computational aspects of the project was provided by the Technological Innovation Agency (TIA) of the Department of Science and Technology of South Africa. The views and findings of this investigation are those of the authors and do not reflect or represent any policies of the TIA funder. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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EE was responsible for the experimental design on fatigue in the cohort of patients, interaction with the physicians and for the collection of the samples and the biochemical analysis, as well as data collection from the questionnaires. SM did the 1H-NMR analysis and data generation, and provided the quantitative metabolite information on the detoxification challenge in the selected cases. FES did the statistical analysis on the link between the medical and fatigue scales. MvR did all pre-processing of the data and provided the univariate and multivariate analysis of all data. CV provided the input for the clinical aspects of the study. CJR participated in all areas of the research, data analysis and proposed the original outline of the manuscript, to which all authors provided their expert contributions. All authors have read and approved the final manuscript.
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This study complied with all institutional guidelines of the North-West University as stipulated by the South African Guidelines for Good Clinical Practice Ethical Guidelines for Research, as well as the terms of the Declaration of Helsinki of 1975 (as revised in 2013) for investigation of human participants. Ethical approval was obtained from the Health Research Ethics Committee (HREC) of the North-West University (NWU-00102-12-A1). All written consent was obtained based upon informed decision from all participants. An example of the informed consent form can be found in SI.
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Erasmus, E., Mason, S., van Reenen, M. et al. A laboratory approach for characterizing chronic fatigue: what does metabolomics tell us?. Metabolomics 15, 158 (2019). https://doi.org/10.1007/s11306-019-1620-4
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DOI: https://doi.org/10.1007/s11306-019-1620-4