Insights into metabolite diagnostic biomarkers for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, by Emi Yamano, Yasuyoshi Watanabe and Yosky Kataoka in Int. J. Mol. Sci. 2021, 22(7), 3423; [doi.org/10.3390/ijms22073423] 26 March 2021
(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months.
Establishing a biomarker for the objective diagnosis is urgently needed to treat a lot of patients. Recently, research on ME/CFS using metabolome analysis methods has been increasing. Here, we overview recent findings concerning the metabolic features in patients with ME/CFS and the animal models which contribute to the development of diagnostic biomarkers for ME/CFS and its treatment. In addition, we discuss future perspectives of studies on ME/CFS.
Table 2. Summary of major biochemical pathways with significant metabolites across patients with ME/CFS:
Common metabolic fluctuations were observed in fatigued animal models and human patients with ME/CFS and these findings could contribute to the elucidation of the pathophysiology of ME/CFS. Biomarker research, to distinguish between patients with ME/CFS and healthy individuals, is still evolving.
In previous studies, reactive oxygen metabolite-derived compounds (d-ROMs)  in the blood, exosomes and inclusion proteins/micro RNAs , monocyte number, and lipoprotein profiles have been reported to be informative markers for discriminating patients with ME/CFS from healthy controls . Furthermore, inflammation and immune system activation have been suggested by many previous studies to be the root causes of ME/CFS, and the results from many such studies have shown elevation of cytokines and lymphokines in plasma .
Using positron emission tomography (PET), neuroinflammation was detected in wide-spread brain regions of patients with ME/CFS, which was associated with the severity of the specific neuro-psychologic symptoms .
We believe that in future, it will be possible to establish highly precise objective diagnostic biomarkers for ME/CFS, exhibiting diverse pathologies through the implementation of research that would integrate metabolomic markers reflecting the specific metabolism underlying the pathophysiology of fatigue with highly precise in vivo biomarkers.