Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS

作者：Xiaoyu Che, Amit Kumar Ranjan, Cheng Guo, Keming Zhang, Rochelle Goldsmith, Susan M. Levine, Kegan James Moneghetti, Yali Zhai, Lixin Ge, Nischay Mishra, Mady Hornig, Lucinda Bateman, Nancy G. Klimas, José Gilberto Montoya, Daniel L. Peterson, Sabra L. Klein, Oliver Fiehn, Anthony L. Komaroff, Walter Ian Lipkin · 发表于：npj Metabolic Health and Disease · 年份：2025 · DOI：10.1038/s44324-025-00079-w · 被引用次数：15 · 研究领域：Fibromyalgia and Chronic Fatigue Syndrome Research、Exercise and Physiological Responses、Long-Term Effects of COVID-19

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue, post-exertional malaise (PEM), and cognitive dysfunction. ME/CFS patients often report a prodrome consistent with infection. We present a multi-omics analysis based on plasma metabolomic and proteomic profiling, and immune responses to microbial stimulation, before and after exercise. We report evidence of an exaggerated innate immune response after exposure to microbial antigens; impaired energy production involving the citric acid cycle, beta-oxidation of fatty acids, and urea cycle energy production from amino acids; systemic inflammation linked to lipid abnormalities; disrupted extracellular matrix homeostasis with release of endogenous ligands that promote inflammation; reduced cell-cell adhesion and associated gut dysbiosis; complement activation; redox imbalance reflected by disturbances in copper-dependent antioxidant pathways; and dysregulation of tryptophan-serotonin-kynurenine pathways. Many abnormalities were worse following exercise and correlated with the intensity of symptoms. Our findings may inform development of targeted therapeutic interventions for ME/CFS and PEM.