Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles

Emi Yamano, Masahiro Sugimoto, Akiyoshi Hirayama, Satoshi Kume, Masanori Yamato, Guanghua Jin, Seiki Tajima, Nobuhito Goda, Kazuhiro Iwai, Sanae Fukuda, Kouzi Yamaguti, Hirohiko Kuratsune, Tomoyoshi Soga, Yasuyoshi Watanabe, Yosky Kataoka

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    Abstract

    Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711-0.890, P < 0.0001) and 0.750 (95% CI: 0.584-0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma.

    Original languageEnglish
    Article number34990
    JournalScientific Reports
    Volume6
    DOIs
    Publication statusPublished - 2016 Oct 11

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    ASJC Scopus subject areas

    • General

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    Yamano, E., Sugimoto, M., Hirayama, A., Kume, S., Yamato, M., Jin, G., Tajima, S., Goda, N., Iwai, K., Fukuda, S., Yamaguti, K., Kuratsune, H., Soga, T., Watanabe, Y., & Kataoka, Y. (2016). Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles. Scientific Reports, 6, [34990]. https://doi.org/10.1038/srep34990