Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrom...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/14/7906 |
| _version_ | 1797433463160176640 |
|---|---|
| author | Xiaoyu Che Christopher R. Brydges Yuanzhi Yu Adam Price Shreyas Joshi Ayan Roy Bohyun Lee Dinesh K. Barupal Aaron Cheng Dana March Palmer Susan Levine Daniel L. Peterson Suzanne D. Vernon Lucinda Bateman Mady Hornig Jose G. Montoya Anthony L. Komaroff Oliver Fiehn W. Ian Lipkin |
| author_facet | Xiaoyu Che Christopher R. Brydges Yuanzhi Yu Adam Price Shreyas Joshi Ayan Roy Bohyun Lee Dinesh K. Barupal Aaron Cheng Dana March Palmer Susan Levine Daniel L. Peterson Suzanne D. Vernon Lucinda Bateman Mady Hornig Jose G. Montoya Anthony L. Komaroff Oliver Fiehn W. Ian Lipkin |
| author_sort | Xiaoyu Che |
| collection | DOAJ |
| description | Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (<i>p</i> < 0.001), phosphatidylcholines (<i>p</i> < 0.001) and sphingomyelins (<i>p</i> < 0.001), and elevated levels of dicarboxylic acids (<i>p</i> = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease. |
| first_indexed | 2024-03-09T10:17:22Z |
| format | Article |
| id | doaj.art-7bd8240334b149ac94bd093bbdb615ee |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:17:22Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7bd8240334b149ac94bd093bbdb615ee2023-12-01T22:16:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314790610.3390/ijms23147906Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue SyndromeXiaoyu Che0Christopher R. Brydges1Yuanzhi Yu2Adam Price3Shreyas Joshi4Ayan Roy5Bohyun Lee6Dinesh K. Barupal7Aaron Cheng8Dana March Palmer9Susan Levine10Daniel L. Peterson11Suzanne D. Vernon12Lucinda Bateman13Mady Hornig14Jose G. Montoya15Anthony L. Komaroff16Oliver Fiehn17W. Ian Lipkin18Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USAUC Davis Genome Center—Metabolomics, University of California, Davis, CA 95616, USADepartment of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USADepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USADepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USALevine Clinic, New York, NY 10021, USASierra Internal Medicine at Incline Village, Incline Village, NV 89451, USABateman Horne Center, Salt Lake City, UT 84102, USABateman Horne Center, Salt Lake City, UT 84102, USADepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USASutter Health Palo Alto Medical Foundation, Palo Alto, CA 94301, USAHarvard Medical School, Brigham and Women’s Hospital, Boston, MA 02115, USAUC Davis Genome Center—Metabolomics, University of California, Davis, CA 95616, USACenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USAMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (<i>p</i> < 0.001), phosphatidylcholines (<i>p</i> < 0.001) and sphingomyelins (<i>p</i> < 0.001), and elevated levels of dicarboxylic acids (<i>p</i> = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.https://www.mdpi.com/1422-0067/23/14/7906myalgic encephalomyelitischronic fatigue syndromemetabolomicsbiomarkerperoxisomecytidine-5′-diphosphocholine pathway |
| spellingShingle | Xiaoyu Che Christopher R. Brydges Yuanzhi Yu Adam Price Shreyas Joshi Ayan Roy Bohyun Lee Dinesh K. Barupal Aaron Cheng Dana March Palmer Susan Levine Daniel L. Peterson Suzanne D. Vernon Lucinda Bateman Mady Hornig Jose G. Montoya Anthony L. Komaroff Oliver Fiehn W. Ian Lipkin Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome International Journal of Molecular Sciences myalgic encephalomyelitis chronic fatigue syndrome metabolomics biomarker peroxisome cytidine-5′-diphosphocholine pathway |
| title | Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome |
| title_full | Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome |
| title_fullStr | Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome |
| title_full_unstemmed | Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome |
| title_short | Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome |
| title_sort | metabolomic evidence for peroxisomal dysfunction in myalgic encephalomyelitis chronic fatigue syndrome |
| topic | myalgic encephalomyelitis chronic fatigue syndrome metabolomics biomarker peroxisome cytidine-5′-diphosphocholine pathway |
| url | https://www.mdpi.com/1422-0067/23/14/7906 |
| work_keys_str_mv | AT xiaoyuche metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT christopherrbrydges metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT yuanzhiyu metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT adamprice metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT shreyasjoshi metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT ayanroy metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT bohyunlee metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT dineshkbarupal metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT aaroncheng metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT danamarchpalmer metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT susanlevine metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT daniellpeterson metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT suzannedvernon metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT lucindabateman metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT madyhornig metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT josegmontoya metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT anthonylkomaroff metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT oliverfiehn metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome AT wianlipkin metabolomicevidenceforperoxisomaldysfunctioninmyalgicencephalomyelitischronicfatiguesyndrome |