It is widely accepted that the pathophysiology and treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) could be considerably improved. The heterogeneity of ME/CFS and the confusion over its classification have undoubtedly contributed to this, although this would seem a consequence of the complexity of the array of ME/CFS presentations and high levels of diverse comorbidities. This article reviews the biological underpinnings of ME/CFS presentations, including the interacting roles of the gut microbiome/permeability, endogenous opioidergic system, immune cell mitochondria, autonomic nervous system, microRNA-155, viral infection/re-awakening and leptin as well as melatonin and the circadian rhythm. This details not only relevant pathophysiological processes and treatment options, but also highlights future research directions. Due to the complexity of interacting systems in ME/CFS pathophysiology, clarification as to its biological underpinnings is likely to considerably contribute to the understanding and treatment of other complex and poorly managed conditions, including fibromyalgia, depression, migraine, and dementia. The gut and immune cell mitochondria are proposed to be two important hubs that interact with the circadian rhythm in driving ME/CFS pathophysiology.

人们普遍认为，肌痛性脑脊髓炎/慢性疲劳综合征 (ME/CFS) 的病理生理学和治疗可以得到显着改善。ME/CFS 的异质性及其分类的混乱无疑促成了这一点，尽管这似乎是 ME/CFS 表现形式的复杂性和高度多样的合并症的结果。本文回顾了 ME/CFS 表现的生物学基础，包括肠道微生物组/渗透性、内源性阿片能系统、免疫细胞线粒体、自主神经系统、microRNA-155、病毒感染/再唤醒和瘦素以及瘦素的相互作用褪黑激素和昼夜节律。这不仅详细说明了相关的病理生理过程和治疗方案，而且还强调了未来的研究方向。由于 ME/CFS 病理生理学中相互作用系统的复杂性，对其生物学基础的澄清可能会大大有助于理解和治疗其他复杂且管理不善的疾病，包括纤维肌痛、抑郁症、偏头痛和痴呆症。肠道和免疫细胞线粒体被认为是在驱动 ME/CFS 病理生理学中与昼夜节律相互作用的两个重要枢纽。