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

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 ba...

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Bibliographic Details
Published in:	Scientific reports Vol. 8; no. 1; pp. 10056 - 11
Main Authors:	Nagy-Szakal, Dorottya, Barupal, Dinesh K., Lee, Bohyun, Che, Xiaoyu, Williams, Brent L., Kahn, Ellie J. R., Ukaigwe, Joy E., Bateman, Lucinda, Klimas, Nancy G., Komaroff, Anthony L., Levine, Susan, Montoya, Jose G., Peterson, Daniel L., Levin, Bruce, Hornig, Mady, Fiehn, Oliver, Lipkin, W. Ian
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 03-07-2018 Nature Publishing Group
Subjects:	631/326 692/4017 692/617/375 82/58 Carnitine Ceramide Choline Chronic fatigue syndrome Cognitive ability Encephalomyelitis Fatigue Fever Humanities and Social Sciences Intestine Intolerance Irritable bowel syndrome Lymphadenopathy Metabolites Metabolomics multidisciplinary Pathogenesis Phenotypes Plasma levels Prediction models Science Science (multidisciplinary) Sleep
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-018-28477-9