Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism

Abstract

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.

Early molecular correlates of adverse events following yellow fever vaccination

“…They have previously been shown to be involved in the initiation and modulation of visceral, cutaneous, and MSK neuropathic as well as inflammatory pain following trauma and infection (22). They have also been associated with myalgic encephalomyelitis (23)(24)(25)(26). In contrast, genes related to DNA synthesis and cell cycle regulation were specifically downregulated in those with MSK AEs (Figure 4, E and H, and Supplemental Table 6).…”

A novel mutation in Slc2a4 as a mouse model of fatigue

“…Like fatigue in other patient populations, fatigue in diabetes is associated with physiological, psychological and lifestyle variables, but may be exacerbated by fluctuations in blood glucose levels and homeostasis. There is also some evidence suggestive of aberrant metabolic responses in CFS patients, with abnormalities in energy and sugar metabolism identified in some patients . However, these studies are not conclusive and there are other potential causes of CFS, including autoimmune disease .…”

“…Mice from two N ‐ethyl‐ N ‐nitrosourea (ENU) lines show abnormal, low amplitude voluntary wheel‐running activity patterns. Circadian activity patterns are double plotted for ease of visualization, with each horizontal line representing 48 hours and successive days plotted along the Y‐axis. Wheel revolutions are depicted as black marks on the horizontal lines.…”

“…There is also some evidence suggestive of aberrant metabolic responses in CFS patients, with abnormalities in energy and sugar metabolism identified in some patients. 95 However, these studies are not conclusive and there are other potential causes of CFS, including autoimmune disease. 96 Nonetheless, the identification of additional abnormalities in metabolic pathways in CFS, both as candidates for treatment options and as potential biological markers for differential diagnoses, have recently received renewed scientific interest and our data suggest they may be a fruitful path for CFS therapies.…”

Inflammation correlates with symptoms in chronic fatigue syndrome

“…Recent metabolomics studies have found deficits in the pathways that generate energy from simple sugars, fatty acids, and amino acids (6)(7)(8)(9). Indeed, one study of over 600 metabolites, published in PNAS, found that the levels of most were unusually low, as occurs in states of hibernation (6).…”