{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T00:24:45Z","timestamp":1793924685939,"version":"4.8.0"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Medicine Foundation","award":["202101AS070058"],"award-info":[{"award-number":["202101AS070058"]}]},{"name":"Yunnan Ten Thousand Talents Plan Young &amp; Elite Talents Project","award":["202101AS070058"],"award-info":[{"award-number":["202101AS070058"]}]},{"name":"Yunnan Fundamental Research Projects","award":["202101AS070058"],"award-info":[{"award-number":["202101AS070058"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) and Long COVID are complex multisystem conditions that pose significant challenges in healthcare. Accumulated research evidence suggests that ME\/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions. This study aims to systematically explore shared metabolic disturbances in the muscle tissue of patients. Utilizing genome-wide metabolic modeling, we identified key metabolic irregularities in the muscle of patients with ME\/CFS, notably the downregulation of the alanine and aspartate metabolism pathway and the arginine and proline metabolism pathway. Further, in silico knockout analyses suggested that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies. In addition, assessments of metabolomic levels in Long COVID patients also showed the significant downregulation of ASP during post-exertional malaise (PEM) in both muscle and blood. Consequently, we propose that a combination of l-ornithine and l-aspartate (LOLA) is a potential candidate to alleviate metabolic symptoms in ME\/CFS and Long COVID for future clinical trials.<\/jats:p>","DOI":"10.3390\/ijms26136082","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T03:53:02Z","timestamp":1750823582000},"page":"6082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME\/CFS and Long COVID"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-6613","authenticated-orcid":false,"given":"Gong-Hua","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Evolution and Animal Models, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ\/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Fei","family":"Han","sequence":"additional","affiliation":[{"name":"Computational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9228-7780","authenticated-orcid":false,"given":"Efthymios","family":"Kalafatis","sequence":"additional","affiliation":[{"name":"Independent Researcher, 185 37 Pireas, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6046-4494","authenticated-orcid":false,"given":"Qing-Peng","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution and Animal Models, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ\/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4944-6380","authenticated-orcid":false,"given":"Wenzhong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Computational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","unstructured":"Board on the Health of Select Populations, Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (2015). 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