Germain Arnaud, Ruppert David, Levine Susan M, Hanson Maureen R
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Department of Statistical Science and School of Operations Research and Information Engineering, Cornell University, Ithaca, NY 14853, USA.
Mol Biosyst. 2017 Jan 31;13(2):371-379. doi: 10.1039/c6mb00600k.
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.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）仍然是一种缺乏生物标志物或简单客观检测方法的连续性谱系疾病，因此依赖于根据一组症状进行诊断，以将各种脑和身体疾病与ME/CFS联系起来。尽管最近的研究显示了各种受影响的途径，但ME/CFS的潜在基础尚未确立。在这项初步研究中，我们比较了一个发现队列中17例患者和15例匹配对照的血浆代谢特征，并探索了基因、转录本和蛋白质之间复杂相互作用后可能产生的代谢扰动。这种研究ME/CFS复杂症状阵列及其潜在基础的方法揭示了361种代谢物中有74种差异累积（P<0.05），经统计校正后有35种显著改变（Q<0.15）。后一组包括几种与能量相关的必需化合物，理论上它们可能与ME/CFS患者普遍存在的能量缺乏有关。通路分析指出了一些对患者有高影响并因此可能存在干扰的通路，主要是牛磺酸代谢和甘油磷脂代谢，以及初级胆汁酸代谢、乙醛酸和二羧酸代谢以及其他一些通路，所有这些通路都广泛参与脂肪酸代谢。发现嘌呤（包括ADP和ATP）、嘧啶和几种氨基酸代谢途径受到显著干扰。最后，葡萄糖和草酰乙酸是两种主要受影响的代谢物，它们对糖和能量水平有重大影响。我们的工作为ME/CFS的诊断和潜在机制的理解提供了一条前瞻性途径。
