ME/CFS Mechanisms
A structured map of the leading biological pathways implicated in ME/CFS. Explore immune, metabolic, vascular, autonomic, and neuroinflammatory mechanisms — and how they connect to symptoms and subtypes.
Neuroinflammation
Chronic microglial activation, neuroimmune signaling, and inflammatory mediators in CSF and brain imaging indicate central inflammation.
Key Findings:
- Microglial activation on PET
- CSF immune abnormalities
- Neuroimmune overlap with Long COVID
📄 5 supporting papers
Autonomic Dysregulation / OI
Broad evidence for orthostatic intolerance, impaired cerebral blood flow, and autonomic control dysfunction.
Key Findings:
- Reduced cerebral blood flow
- High prevalence of OI/POTS
- Symptom improvement with volume support
📄 5 supporting papers
Mitochondrial Energy Impairment
Altered oxidative phosphorylation, PDH inhibition, and hypometabolic cell state in subsets.
Key Findings:
- Reduced ATP production
- Redox abnormalities
- Metabolic trap hypothesis support
📄 5 supporting papers
Immune Dysfunction & Viral Reactivation
Immune exhaustion, NK dysfunction, and herpesvirus activity in subsets.
Key Findings:
- Low NK cytotoxicity
- Herpesvirus reactivation signals
- T-cell exhaustion profile
📄 5 supporting papers
Neurovascular Dysfunction
Endothelial dysfunction and cerebral hypoperfusion similar to Long COVID.
Key Findings:
- Reduced brain perfusion
- Endothelial dysfunction markers
- Exercise-related perfusion decline
📄 5 supporting papers
HPA Axis / Hormonal Dysregulation
Flattened cortisol rhythms and stress axis dysregulation in subsets.
Key Findings:
- Blunted cortisol awakening response
- Stress sensitivity signatures
- HPA–immune cross-talk
📄 5 supporting papers
Gut–Brain–Immune Axis & Microbiome
Dysbiosis, leaky gut, immune activation from microbial products.
Key Findings:
- Low butyrate producers
- Microbial translocation markers (LPS, zonulin)
- Persistent dysbiosis in Long COVID mirrors ME/CFS
📄 5 supporting papers
Oxidative & Nitrosative Stress
Oxidative damage, nitrosative stress, mitochondrial redox imbalance.
Key Findings:
- Elevated reactive oxygen species
- Nitrosative stress markers
- Links to PEM and metabolic suppression
📄 5 supporting papers