Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics
Open accessAbstract
The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.
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More recent studies have found abnormalities in cerebrospinal fluid independent of psychiatric diagnoses, consistent with neuroinflammation.
“More recent studies have found abnormalities in cerebrospinal fluid independent of psychiatric diagnoses64–66, consistent with neuroinflammation.”
From Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically-relevant Phenotyping of Women with Chronic Fatigue Syndrome (2019) · cites this paper as [66]
The Results describe plasma metabolomic differences, and the Discussion discusses a possible blood–brain barrier mechanism. Neither section reports cerebrospinal fluid abnormalities or tests whether findings are independent of psychiatric diagnoses; searches for those terms found no relevant passage in our copy. Page numbers were not available. (LLM, conf=0.76)
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References 56 · Cited by 120
Research works printed but not linked: 1
- [1]Institute of Medicine, I. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington, DC: The National Academies Press. (2015). 25695122
- Authors
- Nagy-Szakal, D., Barupal, D. K., Lee, B., Che, X., Williams, B. L., Kahn, E. J. R., Ukaigwe, J. E., Bateman, L., Klimas, N. G., Komaroff, A. L., Levine, S., Montoya, J. G., Peterson, D. L., Levin, B., Hornig, M., Fiehn, O., & Lipkin, W. I.
- Affiliations
- University of California, Davis (US)
- Columbia University (US)
- Bateman Horne Center (US)
- Nova Southeastern University (US)
- Brigham and Women's Hospital (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Fiehn, Oliver
- Lipkin, W. Ian
- ORCID
- Venue
- Scientific Reports
- Published
- 2018-07-03
- Volume
- 8
- Issue
- 1
- Pages
- 10056-10056
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6030047
- OpenAlex
- W2811501886
- Cited by
- 120
- References
- 56
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 15 · 2023: 12 · 2022: 10 · 2021: 15 · 2020: 20 · 2019: 9 · 2018: 6
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- National Institutes of Health (DK097154, AI109761)
- National Institute of Allergy and Infectious Diseases (U19AI109761, R56AI120724)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097154)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- chronic fatigue syndrome, irritable bowel syndrome, plasma metabolomics, biomarker discovery, ceramide, choline, L-carnitine, disease phenotypes, diagnostic prediction model
- MeSH terms
- Fatigue, Feces, Female, Humans, Male, Middle Aged, Phenotype, Sleep Wake Disorders, Biomarkers, Fatigue Syndrome, Chronic, Case-Control Studies, Irritable Bowel Syndrome, Metabolomics, Metagenomics
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