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Article

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

1
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
2
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
3
UC Davis Genome Center—Metabolomics, University of California, Davis, CA 95616, USA
4
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
5
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
6
Levine Clinic, New York, NY 10021, USA
7
Sierra Internal Medicine at Incline Village, Incline Village, NV 89451, USA
8
Bateman Horne Center, Salt Lake City, UT 84102, USA
9
Sutter Health Palo Alto Medical Foundation, Palo Alto, CA 94301, USA
10
Harvard Medical School, Brigham and Women’s Hospital, Boston, MA 02115, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Godfrey Getz
Int. J. Mol. Sci. 2022, 23(14), 7906; https://doi.org/10.3390/ijms23147906
Received: 11 June 2022 / Revised: 14 July 2022 / Accepted: 16 July 2022 / Published: 18 July 2022
(This article belongs to the Special Issue Metabolomics in Health and Disease)
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease. View Full-Text
Keywords: myalgic encephalomyelitis; chronic fatigue syndrome; metabolomics; biomarker; peroxisome; cytidine-5′-diphosphocholine pathway; tricarboxylic acid cycle myalgic encephalomyelitis; chronic fatigue syndrome; metabolomics; biomarker; peroxisome; cytidine-5′-diphosphocholine pathway; tricarboxylic acid cycle
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MDPI and ACS Style

Che, X.; Brydges, C.R.; Yu, Y.; Price, A.; Joshi, S.; Roy, A.; Lee, B.; Barupal, D.K.; Cheng, A.; Palmer, D.M.; Levine, S.; Peterson, D.L.; Vernon, S.D.; Bateman, L.; Hornig, M.; Montoya, J.G.; Komaroff, A.L.; Fiehn, O.; Lipkin, W.I. Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int. J. Mol. Sci. 2022, 23, 7906. https://doi.org/10.3390/ijms23147906

AMA Style

Che X, Brydges CR, Yu Y, Price A, Joshi S, Roy A, Lee B, Barupal DK, Cheng A, Palmer DM, Levine S, Peterson DL, Vernon SD, Bateman L, Hornig M, Montoya JG, Komaroff AL, Fiehn O, Lipkin WI. Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. International Journal of Molecular Sciences. 2022; 23(14):7906. https://doi.org/10.3390/ijms23147906

Chicago/Turabian Style

Che, Xiaoyu, Christopher R. Brydges, Yuanzhi Yu, Adam Price, Shreyas Joshi, Ayan Roy, Bohyun Lee, Dinesh K. Barupal, Aaron Cheng, Dana March Palmer, Susan Levine, Daniel L. Peterson, Suzanne D. Vernon, Lucinda Bateman, Mady Hornig, Jose G. Montoya, Anthony L. Komaroff, Oliver Fiehn, and W. Ian Lipkin. 2022. "Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" International Journal of Molecular Sciences 23, no. 14: 7906. https://doi.org/10.3390/ijms23147906

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