Citation	Description of Research
Walitt et al. [40]	Brain and Nervous System Abnormalities NIH Study on Brain and Immune System Dysregulation (2024): An in-depth study by the National Institutes of Health identified abnormalities in brain regions such as the temporal-parietal junction and motor cortex in ME/CFS patients. Functional MRI scans revealed altered activity in these areas, suggesting a neurological basis for the fatigue experienced by patients. Additionally, immune system irregularities were observed, indicating a potential link between immune activation and brain function disruptions.
Eaton-Fitch et al. [41]	Immune System Dysregulation Researchers at Griffith University conducted a study analyzing immune gene expression in ME/CFS and Long COVID patients. The findings highlighted a state of immune exhaustion characterized by down-regulated interferon signaling and immunoglobulin genes in ME/CFS patients. This suggests a suppressed immune response, which may contribute to the chronic nature of the disease.
National Institutes of Health [42]	Metabolic and Mitochondrial Dysfunction The study found significant metabolic alterations in the peripheral blood mononuclear cells of ME/CFS patients. These changes included decreased glycolysis, reduced mitochondrial respiration, and impaired fatty acid oxidation, indicating a disruption in cellular energy production mechanisms.
Xiong et al. [43]	Gut Microbiome Imbalances The gut microbiome of ME/CFS patients was found to have distinct differences in microbial and metabolic pathways compared to healthy individuals. Notably, a reduction in butyrate-producing bacteria was observed, which may impact intestinal health and systemic inflammation.
Maksoud et al. [44]	An evaluation of studies of potential biomarkers for ME/CFS found consistent alterations of amino acid metabolism, mitochondrial function, and altered oxidative stress markers in patients, suggesting these could serve as potential diagnostic indicators.
Rowe et al. [21] Hakim et al. [45] National Institutes of Health [42]	Study finds a higher occurrence of Ehlers-Danlos Syndrome (EDS), particularly joint hypermobility, with ME/CFS Joint hypermobility is found to be significantly more common in adolescents with chronic fatigue than in controls. Patients with Ehlers-Danlos syndrome—Hypermobile type often met criteria for CFS. 12–19% of ME/CFS patients may have EDS, and 50–81% show hypermobility—indicating significant comorbidity.
Van Campen et al. [6]	Episodic Reduction in Cerebral Blood Flow With Head Tilt About 90% of ME/CFS patients showed abnormal cerebral blood flow reduction during tilt testing, even in the absence of traditional heart rate or blood pressure abnormalities, suggesting orthostatic intolerance as a contributor to the pathophysiology of ME/CFS.