A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease usually presenting after infection. Emerging evidence supports that  energy metabolism is affected in ME/CFS, but a unifying metabolic phenotype has  not been firmly established. We performed global metabolomics, lipidomics, and  hormone measurements, and we used exploratory data analyses to compare serum from  83 patients with ME/CFS and 35 healthy controls. Some changes were common in the  patient group, and these were compatible with effects of elevated energy strain  and altered utilization of fatty acids and amino acids as catabolic fuels. In  addition, a set of heterogeneous effects reflected specific changes in 3 subsets  of patients, and 2 of these expressed characteristic contexts of deregulated  energy metabolism. The biological relevance of these metabolic phenotypes  (metabotypes) was supported by clinical data and independent blood analyses. In  summary, we report a map of common and context-dependent metabolic changes in  ME/CFS, and some of them presented possible associations with clinical patient  profiles. We suggest that elevated energy strain may result from  exertion-triggered tissue hypoxia and lead to systemic metabolic adaptation and  compensation. Through various mechanisms, such metabolic dysfunction represents a  likely mediator of key symptoms in ME/CFS and possibly a target for supportive  intervention.