title: Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles.
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.
authors.affiliation: Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Yamano
authors.affiliation: Institute for Advanced Biosciences, Keio University, 246-2 Mizukami Kakuganji, Tsuruoka Yamagata 997-0052, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Institute for Advanced Biosciences, Keio University, 246-2 Mizukami Kakuganji, Tsuruoka Yamagata 997-0052, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirayama
authors.affiliation: Cellular Function Imaging Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kume
authors.affiliation: Cellular Function Imaging Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamato
authors.affiliation: Cellular Function Imaging Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Jin
authors.affiliation: Cellular Function Imaging Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.|Hyogo Children's Sleep and Development Medical Research Center, Hyogo Rehabilitation Centre Central Hospital, 1070 Akebono-cho, Nishi-ku, Kobe, Hyogo 651-2181, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Tajima
authors.affiliation: Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.affiliation: Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.|Department of Health Science, Kansai University of Welfare Sciences, 3-11-1 Asahigaoka, Kashihara, Osaka 582-0026, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.|Department of Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Kouzi
authors.initials: K
authors.lastname: Yamaguti
authors.affiliation: Department of Health Science, Kansai University of Welfare Sciences, 3-11-1 Asahigaoka, Kashihara, Osaka 582-0026, Japan.|Department of Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Kuratsune
authors.affiliation: Institute for Advanced Biosciences, Keio University, 246-2 Mizukami Kakuganji, Tsuruoka Yamagata 997-0052, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.|Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.|Cellular Function Imaging Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yosky
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D000328:Adult; D044466:Asian People; D001685:Biological Factors / Q000032:analysis*; D015415:Biomarkers / Q000097:blood*; D015673:Fatigue Syndrome, Chronic / Q000175:diagnosis* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D012372:ROC Curve; D055815:Young Adult
chemical_list: D001685:Biological Factors; D015415:Biomarkers