Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics

Dorottya Nagy-Szakal; Dinesh K. Barupal; Bohyun Lee; Xiaoyu Che; Brent L. Williams; Ellie J.R. Kahn; Joy E. Ukaigwe; Lucinda Bateman; Nancy G. Klimas; Anthony L. Komaroff; Susan Levine; Jose G. Montoya; Daniel L. Peterson; Bruce Levin; Mady Hornig; Oliver Fiehn; W. Ian Lipkin

doi:10.1038/s41598-018-28477-9

Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics

Dorottya Nagy-Szakal
, Dinesh K. Barupal
, Bohyun Lee
, Xiaoyu Che
, Brent L. Williams
, Ellie J.R. Kahn
, Joy E. Ukaigwe
, Lucinda Bateman
, Nancy G. Klimas
, Anthony L. Komaroff
, Susan Levine
, Jose G. Montoya
, Daniel L. Peterson
, Bruce Levin
, Mady Hornig
, Oliver Fiehn
, W. Ian Lipkin

Research output: Contribution to journal › Article › peer-review

Abstract

The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.

Original language	English
Article number	10056
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-28477-9
State	Published - Dec 1 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

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Nagy-Szakal, D., Barupal, D. K., Lee, B., Che, X., Williams, B. L., Kahn, E. J. R., Ukaigwe, J. E., Bateman, L., Klimas, N. G., Komaroff, A. L., Levine, S., Montoya, J. G., Peterson, D. L., Levin, B., Hornig, M., Fiehn, O., & Lipkin, W. I. (2018). Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Scientific Reports, 8(1), Article 10056. https://doi.org/10.1038/s41598-018-28477-9

Nagy-Szakal, D, Barupal, DK, Lee, B, Che, X, Williams, BL, Kahn, EJR, Ukaigwe, JE, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, Peterson, DL, Levin, B, Hornig, M, Fiehn, O & Lipkin, WI 2018, 'Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics', Scientific Reports, vol. 8, no. 1, 10056. https://doi.org/10.1038/s41598-018-28477-9

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title = "Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics",

abstract = "The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.",

author = "Dorottya Nagy-Szakal and Barupal, \{Dinesh K.\} and Bohyun Lee and Xiaoyu Che and Williams, \{Brent L.\} and Kahn, \{Ellie J.R.\} and Ukaigwe, \{Joy E.\} and Lucinda Bateman and Klimas, \{Nancy G.\} and Komaroff, \{Anthony L.\} and Susan Levine and Montoya, \{Jose G.\} and Peterson, \{Daniel L.\} and Bruce Levin and Mady Hornig and Oliver Fiehn and Lipkin, \{W. Ian\}",

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AU - Nagy-Szakal, Dorottya

AU - Barupal, Dinesh K.

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AU - Che, Xiaoyu

AU - Williams, Brent L.

AU - Kahn, Ellie J.R.

AU - Ukaigwe, Joy E.

AU - Bateman, Lucinda

AU - Klimas, Nancy G.

AU - Komaroff, Anthony L.

AU - Levine, Susan

AU - Montoya, Jose G.

AU - Peterson, Daniel L.

AU - Levin, Bruce

AU - Hornig, Mady

AU - Fiehn, Oliver

AU - Lipkin, W. Ian

PY - 2018/12/1

Y1 - 2018/12/1

N2 - The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.

AB - The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.

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Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics

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