Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity.
Beentjes, Sjoerd Viktor, Miralles Méharon, Artur, Kaczmarczyk, Julia et al. · EMBO molecular medicine · 2025 · DOI
Quick Summary
Researchers found multiple blood markers that distinguish ME/CFS patients from healthy people, including signs of inflammation, insulin problems, and liver issues. Importantly, these differences were NOT caused by patients being physically inactive—they are genuine biological changes related to the disease itself. While no single blood test can diagnose ME/CFS yet, these findings suggest that a combination of blood markers could eventually provide objective diagnosis.
Why It Matters
This study provides crucial biological evidence that ME/CFS is a real disease with measurable physical abnormalities, not simply deconditioning from inactivity—a persistent misconception. The identification of replicable biomarkers across two large biobanks moves the field closer to objective diagnosis, which could reduce diagnostic delays and improve patient care. For researchers, these findings deepen understanding of ME/CFS pathophysiology and identify potential therapeutic targets.
Observed Findings
- 116 molecular and cellular traits significantly differed between ME/CFS cases and controls in both female and male cohorts
- Biomarkers indicated chronic inflammation, insulin resistance, and liver disease pathways
- 9 of 14 traits identified in UK Biobank replicated in the All-of-Us cohort
- Patients with post-exertional malaise showed stronger biomarker differences than those without
- Physical activity level mediated the association between ME/CFS status and only 1 of 3,237 measured traits
Inferred Conclusions
- ME/CFS is associated with reproducible biological abnormalities that cannot be explained by physical inactivity alone
- Chronic inflammation and metabolic dysfunction are central features of ME/CFS pathophysiology
- A combination of blood biomarkers may eventually enable objective diagnosis, though individual markers lack sufficient specificity
- Post-exertional malaise may represent a more severe biological phenotype with stronger systemic abnormalities
Remaining Questions
- Can a specific biomarker panel be developed with sufficient sensitivity and specificity for clinical diagnostic use?
- Are the identified biomarkers causative of ME/CFS symptoms or secondary consequences of the disease process?
- Do biomarker patterns predict treatment response or disease progression, and do they change with disease remission or recovery?
- How do the identified inflammatory and metabolic pathways specifically relate to post-exertional malaise and other cardinal ME/CFS symptoms?
What This Study Does Not Prove
This study does not prove that any single blood test can diagnose ME/CFS or that these biomarkers cause ME/CFS symptoms. The findings are correlational and do not establish whether inflammation and metabolic dysfunction are primary disease drivers or secondary consequences. The biomarker panel's clinical utility for individual patient diagnosis remains to be determined in prospective validation studies.
Topics
Tags
Metadata
- DOI
- 10.1038/s44321-025-00258-8
- PMID
- 40537675
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 7 April 2026