Evidence for Peroxisomal Dysfunction and Dysregulation of the CDP-Choline Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Autor:	Che X; Center for Infection and Immunity, Mailman School of Public Health; Columbia University, New York, NY, United States.; Department of Biostatistics, Mailman School of Public Health, Columbia University; New York, NY, United States., Brydges CR; UC Davis Genome Center - Metabolomics, University of California, Davis; Davis, CA, United States., Yu Y; Department of Biostatistics, Mailman School of Public Health, Columbia University; New York, NY, United States., Price A; Center for Infection and Immunity, Mailman School of Public Health; Columbia University, New York, NY, United States., Joshi S; Center for Infection and Immunity, Mailman School of Public Health; Columbia University, New York, NY, United States., Roy A; Center for Infection and Immunity, Mailman School of Public Health; Columbia University, New York, NY, United States., Lee B; Center for Infection and Immunity, Mailman School of Public Health; Columbia University, New York, NY, United States., Barupal DK; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai; New York, United States., Cheng A; Center for Infection and Immunity, Mailman School of Public Health; Columbia University, New York, NY, United States., Palmer DM; Department of Epidemiology, Mailman School of Public Health, Columbia University; New York, NY, United States., Levine S; Levine Clinic; New York, NY, United States., Peterson DL; Sierra Internal Medicine at Incline Village; Incline Village, NV, United States., Vernon SD; Bateman Horne Center; Salt Lake City, UT, United States., Bateman L; Bateman Horne Center; Salt Lake City, UT, United States., Hornig M; Department of Epidemiology, Mailman School of Public Health, Columbia University; New York, NY, United States., Montoya JG; Sutter Health Palo Alto Medical Foundation; Palo Alto, CA, United States., Komaroff AL; Harvard Medical School, Brigham and Women's Hospital; Boston, MA, United States., Fiehn O; UC Davis Genome Center - Metabolomics, University of California, Davis; Davis, CA, United States., Lipkin WI; Center for Infection and Immunity, Mailman School of Public Health; Columbia University, New York, NY, United States.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2022 Jan 11. Date of Electronic Publication: 2022 Jan 11.
DOI:	10.1101/2021.06.14.21258895
Abstrakt:	Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease that is characterized by unexplained physical fatigue unrelieved by rest. Symptoms also include cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. A syndrome clinically similar to ME/CFS has been reported following well-documented infections with the coronaviruses SARS-CoV and MERS-CoV. At least 10% of COVID-19 survivors develop post acute sequelae of SARS-CoV-2 infection (PASC). Although many individuals with PASC have evidence of structural organ damage, a subset have symptoms consistent with ME/CFS including fatigue, post exertional malaise, cognitive dysfunction, gastrointestinal disturbances, and postural orthostatic intolerance. These common features in ME/CFS and PASC suggest that insights into the pathogenesis of either may enrich our understanding of both syndromes, and could expedite the development of strategies for identifying those at risk and interventions that prevent or mitigate disease. Methods: Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of 888 metabolic analytes in plasma samples of 106 ME/CFS cases and 91 frequency-matched healthy controls. Results: In ME/CFS cases, regression, Bayesian and enrichment analyses revealed evidence of peroxisomal dysfunction with decreased levels of plasmalogens. Other findings included decreased levels of several membrane lipids, including phosphatidylcholines and sphingomyelins, that may indicate dysregulation of the cytidine-5’-diphosphocholine pathway. Enrichment analyses revealed decreased levels of choline, ceramides and carnitines, and increased levels of long chain triglycerides (TG) and hydroxy-eicosapentaenoic acid. Elevated levels of dicarboxylic acids were consistent with abnormalities in the tricarboxylic acid cycle. Using machine learning algorithms with selected metabolites as predictors, we were able to differentiate female ME/CFS cases from female controls (highest AUC=0.794) and ME/CFS cases without self-reported irritable bowel syndrome (sr-IBS) from controls without sr-IBS (highest AUC=0.873). Conclusion: Our findings are consistent with earlier ME/CFS work indicating compromised energy metabolism and redox imbalance, and highlight new abnormalities that may provide insights into the pathogenesis of ME/CFS. One Sentence Summary: Plasma levels of plasmalogens are decreased in patients with myalgic encephalomyelitis/chronic fatigue syndrome suggesting peroxisome dysfunction.
Databáze:	MEDLINE
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