Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Simonato, Manuela, Dall'Acqua, Stefano, Zilli, Caterina et al. · Biomedicines · 2021 · DOI
Quick Summary
This study compared blood samples from 40 people with ME/CFS to 40 healthy people to look for biological differences. Researchers found that ME/CFS patients had different levels of certain molecules related to immune function, gut health, and how the body uses the amino acid tryptophan. These differences were independent of each other, suggesting multiple biological pathways may be disrupted in ME/CFS.
Why It Matters
This study supports the hypothesis that ME/CFS involves dysregulation across multiple independent biological systems—immune, intestinal, and metabolic—rather than a single mechanism. Identifying distinct biomarker signatures could enable better patient stratification for personalized treatment approaches and help researchers understand disease heterogeneity.
Observed Findings
ME/CFS patients had significantly higher IL-17A, FABP-2, and 3-hydroxykynurenine compared to controls.
ME/CFS patients had significantly lower kynurenine and serotonin levels compared to controls.
Altered ratios of kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine suggest abnormal enzyme activity in tryptophan metabolism.
Patients with post-infectious disease onset had lower kynurenine than those with non-infectious onset.
No statistical correlations were found between inflammatory markers, intestinal barrier markers, and tryptophan metabolites.
Inferred Conclusions
Inflammation, intestinal barrier dysfunction, and tryptophan metabolic abnormalities appear to be independently associated with ME/CFS pathogenesis.
Alterations in tryptophan metabolism and IL-17A elevation may relate to energy metabolism dysfunction in ME/CFS.
Combined assessment of these biomarkers could support personalized medicine strategies for ME/CFS patient stratification.
Post-infectious ME/CFS may involve distinct metabolic dysregulation compared to non-infectious onset forms.
Remaining Questions
Do these biomarker changes represent independent disease mechanisms, or are they downstream consequences of a common upstream pathology?
What This Study Does Not Prove
This cross-sectional study cannot establish causation; the observed biomarker changes may be consequences rather than causes of ME/CFS. The lack of correlation between different biomarker categories does not prove they are completely independent—shared upstream causes could still exist. Results are descriptive and require validation in larger, longitudinal cohorts before informing clinical practice.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →