Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a
continuum spectrum disease without biomarkers or simple objective tests, and
therefore relies on a diagnosis from a set of symptoms to link the assortment of
brain and body disorders to ME/CFS. Although recent studies show various
affected pathways, the underlying basis of ME/CFS has yet to be established. In
this pilot study, we compare plasma metabolic signatures in a discovery cohort,
17 patients and 15 matched controls, and explore potential metabolic
perturbations as the aftermath of the complex interactions between genes,
transcripts and proteins. This approach to examine the complex array of symptoms
and underlying foundation of ME/CFS revealed 74 differentially accumulating
metabolites, out of 361 (P<0.05), and 35 significantly
altered after statistical correction (Q<0.15). The latter
list includes several essential energy-related compounds which could
theoretically be linked to the general lack of energy observed in ME/CFS
patients. Pathway analysis points to a few pathways with high impact and
therefore potential disturbances in patients, mainly taurine metabolism and
glycerophospholipid metabolism, combined with primary bile acid metabolism, as
well as glyoxylate and dicarboxylate metabolism and a few other pathways, all
involved broadly in fatty acid metabolism. Purines, including ADP and ATP,
pyrimidines and several amino acid metabolic pathways were found to be
significantly disturbed. Finally, glucose and oxaloacetate were two main
metabolites affected that have a major effect on sugar and energy levels. Our
work provides a prospective path for diagnosis and understanding of the
underlying mechanisms of ME/CFS.