Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review

2018 ◽  
Vol 46 (3) ◽  
pp. 547-553 ◽  
Author(s):  
Cara Tomas ◽  
Julia Newton
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Adenosine Monophosphate ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Unknown Etiology ◽  
Data Sets ◽  
Metabolic Abnormalities ◽  
Research Areas ◽  
Fatigue Syndrome ◽  
Potential Biomarkers

Chronic fatigue syndrome (CFS), commonly known as myalgic encephalomyelitis (ME), is a debilitating disease of unknown etiology. CFS/ME is a heterogeneous disease associated with a myriad of symptoms but with severe, prolonged fatigue as the core symptom associated with the disease. There are currently no known biomarkers for the disease, largely due to the lack of knowledge surrounding the eitopathogenesis of CFS/ME. Numerous studies have been conducted in an attempt to identify potential biomarkers for the disease. This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease. The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5′-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here. Studies outlined in this mini-review show many potential causes for the pathogenesis of CFS/ME and identify many potential metabolic biomarkers for the disease from the aforementioned research areas. The future of CFS/ME research should focus on building on the potential biomarkers for the disease using multi-disciplinary techniques at multiple research sites in order to produce robust data sets. Whether the metabolic changes identified in this mini-review occur as a cause or a consequence of the disease must also be established.

scholarly journals Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study

2018 ◽  
Vol 7 (1) ◽  
pp. 1453730 ◽  
Author(s):  
Jesús Castro-Marrero ◽  
Esther Serrano-Pertierra ◽  
Myriam Oliveira-Rodríguez ◽  
Maria Cleofé Zaragozá ◽  
Alba Martínez-Martínez ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Fatigue Syndrome ◽  
Extracellular Vesicles ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Potential Biomarkers

scholarly journals Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

2011 ◽  
Vol 9 (1) ◽  
pp. 81 ◽  
Author(s):  
Ekua W Brenu ◽  
Mieke L van Driel ◽  
Don R Staines ◽  
Kevin J Ashton ◽  
Sandra B Ramos ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Immunological Abnormalities ◽  
Potential Biomarkers

scholarly journals Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis

2021 ◽  
Vol 15 ◽  
Author(s):  
Adonis Sfera ◽  
Carolina Osorio ◽  
Carlos M. Zapata Martín del Campo ◽  
Shaniah Pereida ◽  
Steve Maurer ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Viral Infections ◽  
Life Quality ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Unknown Etiology ◽  
Host Proteins ◽  
Fatigue Syndrome ◽  
Long Time ◽  
Sleep Abnormalities

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality. In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain. This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness.

scholarly journals Genome-Epigenome Interactions Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

2017 ◽  
Author(s):  
Santiago Herrera ◽  
Wilfred C. de Vega ◽  
David Ashbrook ◽  
Suzanne D. Vernon ◽  
Patrick O. McGowan
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Complex Disease ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Genetic Interactions ◽  
Unknown Etiology ◽  
Immune Functioning ◽  
Fatigue Syndrome ◽  
Close Proximity

ABSTRACTMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an example of a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as with specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, the association between DNA methylation and genetic background in relation to the ME/CFS is currently unknown. In this study we explored this association by characterizing the genomic (~4.3 million SNPs) and epigenomic (~480 thousand CpG loci) variability between populations of ME/CFS patients and healthy controls. We found significant associations of methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation phenotypes associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.

scholarly journals Potential benefits of a ketogenic diet to improve response and recovery from physical exertion in people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A feasibility study

2021 ◽  
Vol 3 (2) ◽  
pp. 33-39
Author(s):  
Jo Cossington ◽  
◽  
Dr. Shelly Coe ◽  
Yaomeng Liu ◽  
Helen Dawes ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Ketogenic Diet ◽  
Energy Production ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Exercise Stress ◽  
Metabolic Abnormalities ◽  
Post Intervention ◽  
Low Carbohydrate Diet ◽  
Fatigue Syndrome

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) affects approximately 250,000 people in the UK. The condition varies in severity causing long-term physical and cognitive fatigue which is not alleviated by rest. Whilst the pathology is not understood, recent evidence suggests metabolic abnormalities may be associated with the manifestation of symptoms, particularly involving the metabolism of glucose and energy production. The use of ketone bodies as an alternative energy substrate may be beneficial to people with ME/CFS, in order to by-pass the glycolytic pathway, enhance energy production and reduce fatiguing outcomes. Study Design and Methods: Using a pragmatic collective case study with repeated measures methodology we investigated the feasibility of following a ketogenic diet and potential effects of the high fat, low carbohydrate diet on response to physical activity in people with ME/CFS (n=3) and healthy controls (n=3) using a submaximal exercise stress test both with and without dietary intervention. Exercise tolerance (mins), rate of oxygen consumption (VO2) to workload (75W), respiratory exchange ratio (RER), rate of perceived effort (RPE) and lactate response were measured throughout and descriptive statistics performed. Results: We found that the ketogenic diet was followed, with compliance higher in the pwME/CFS. Variations in response following the ketogenic diet was observed across individuals in minutes performed, VO2, HR, RER, and RPE post diet but the KD only limited exercise capacity in the control individuals. Individuals responded differently to the KD but group trends have been reported as means and standard deviation. The KD resulted in a decrease in RER at submax in the controls with a mean change of 0.07 from baseline (0.86 ± 0.1) to post intervention (0.79 ± 0.1) compared to a mean change of 0.02 in the ME/CFS from baseline (1.03 ± 0.1) to post intervention (1.01 ± 0.1). A decrease in VO2 (L/min) at submax showed a mean change of 0.06 (L/min) in the pwME/CFS at baseline (1.34 ± 0.1) to post intervention (1.27 ± 0.2) compared to a mean change of 0.07 (L/min) in the controls at baseline (1.40 ± 0.3) to post intervention (1.33 ± 0.2). HR (bpm) at submax decreased in all individuals, with a mean change of 4 (bpm), with pwME/CFS at baseline (139 ± 8.2) to post intervention (135 ± 14) and control individuals at baseline (107 ± 7.8) to intervention (103 ± 3.2). RPE at submax decreased in the pwME/CFS from baseline (6 ± 1.0) to post intervention (5 ± 2.1) whereas the controls increased from baseline (2 ± 1.0) to post intervention (3 ± 1.5). Conclusion: Our observations suggest individualised but metabolic flexibility in healthy individuals is achievable via dietary manipulation showing the ability to switch from glucose to fats under controlled conditions. The different response in substrate utilisation in individuals with ME/CFS suggests that potential metabolic abnormalities may be present in ME/CFS. Further investigation is now warranted in order to assess whether the KD is beneficial for people with ME/CFS

scholarly journals Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

2019 ◽  
Author(s):  
Ece Karhan ◽  
Courtney L Gunter ◽  
Vida Ravanmehr ◽  
Meghan Horne ◽  
Lina Kozhaya ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Fatigue Syndrome ◽  
Cell Subset ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
T Cell Subsets ◽  
Unknown Etiology ◽  
T Cell Subset ◽  
Fatigue Syndrome

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder of unknown etiology, and diagnosis of the disease is largely based on clinical symptoms. We hypothesized that immunological disruption is the major driver of this disease and analyzed a large cohort of ME/CFS patient or control blood samples for differences in T cell subset frequencies and functions. We found that the ratio of CD4+ to CD8+ T cells and the proportion of CD8+ effector memory T cells were increased, whereas NK cells were reduced in ME/CFS patients younger than 50 years old compared to a healthy control group. Remarkably, major differences were observed in Th1, Th2, Th17 and mucosal-associated invariant T (MAIT) T cell subset functions across all ages of patients compared to healthy subjects. While CCR6+ Th17 cells in ME/CFS secreted less IL-17 compared to controls, their overall frequency was higher. Similarly, MAIT cells from patients secreted lower IFNγ, GranzymeA and IL-17 upon activation. Together, these findings suggest chronic stimulation of these T cell populations in ME/CFS patients. In contrast, the frequency of regulatory T cells (Tregs), which control excessive immune activation, was higher in ME/CFS patients. Finally, using a machine learning algorithm called random forest, we determined that the set of T cell parameters analyzed could identify more than 90% of the subjects in the ME/CFS cohort as patients (93% true positive rate or sensitivity). In conclusion, these multiple and major perturbations or dysfunctions in T cell subsets in ME/CFS patients suggest potential chronic infections or microbiome dysbiosis. These findings also have implications for development of ME/CFS specific immune biomarkers and reveal potential targets for novel therapeutic interventions.

scholarly journals Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ludovic Giloteaux ◽  
Adam O’Neal ◽  
Jesús Castro-Marrero ◽  
Susan M. Levine ◽  
Maureen R. Hanson
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Extracellular Vesicles ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Unknown Etiology ◽  
Cytokine Signaling ◽  
Control Group ◽  
Homogeneous Population ◽  
Fatigue Syndrome ◽  
Immune System Dysfunction

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of unknown etiology lasting for a minimum of 6 months but usually for many years, with features including fatigue, cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Dysregulation of cytokine signaling could give rise to many of these symptoms. Cytokines are present in both plasma and extracellular vesicles, but little investigation of EVs in ME/CFS has been reported. Therefore, we aimed to characterize the content of extracellular vesicles (EVs) isolated from plasma (including circulating cytokine/chemokine profiling) from individuals with ME/CFS and healthy controls. Methods We included 35 ME/CFS patients and 35 controls matched for age, sex and BMI. EVs were enriched from plasma by using a polymer-based precipitation method and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and immunoblotting. A 45-plex immunoassay was used to determine cytokine levels in both plasma and isolated EVs from a subset of 19 patients and controls. Linear regression, principal component analysis and inter-cytokine correlations were analyzed. Results ME/CFS individuals had significantly higher levels of EVs that ranged from 30 to 130 nm in size as compared to controls, but the mean size for total extracellular vesicles did not differ between groups. The enrichment of typical EV markers CD63, CD81, TSG101 and HSP70 was confirmed by Western blot analysis and the morphology assessed by TEM showed a homogeneous population of vesicles in both groups. Comparison of cytokine concentrations in plasma and isolated EVs of cases and controls yielded no significant differences. Cytokine-cytokine correlations in plasma revealed a significant higher number of interactions in ME/CFS cases along with 13 inverse correlations that were mainly driven by the Interferon gamma-induced protein 10 (IP-10), whereas in the plasma of controls, no inverse relationships were found across any of the cytokines. Network analysis in EVs from controls showed 2.5 times more significant inter-cytokine interactions than in the ME/CFS group, and both groups presented a unique negative association. Conclusions Elevated levels of 30-130 nm EVs were found in plasma from ME/CFS patients and inter-cytokine correlations revealed unusual regulatory relationships among cytokines in the ME/CFS group that were different from the control group in both plasma and EVs. These disturbances in cytokine networks are further evidence of immune dysregulation in ME/CFS.

scholarly journals Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking Back on Treatments

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 126 ◽  
Author(s):  
Eloy Almenar-Pérez ◽  
Teresa Sánchez-Fito ◽  
Tamara Ovejero ◽  
Lubov Nathanson ◽  
Elisa Oltra
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Biomarker Discovery ◽  
Drug Effects ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Response To Treatment ◽  
Molecular Diagnostic ◽  
Unknown Etiology ◽  
Healthy Population ◽  
Fatigue Syndrome

Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are diseases of unknown etiology presenting complex and often overlapping symptomatology. Despite promising advances on the study of miRNomes of these diseases, no validated molecular diagnostic biomarker yet exists. Since FM and ME/CFS patient treatments commonly include polypharmacy, it is of concern that biomarker miRNAs are masked by drug interactions. Aiming at discriminating between drug-effects and true disease-associated differential miRNA expression, we evaluated the potential impact of commonly prescribed drugs on disease miRNomes, as reported by the literature. By using the web search tools SM2miR, Pharmaco-miR, and repoDB, we found a list of commonly prescribed drugs that impact FM and ME/CFS miRNomes and therefore could be interfering in the process of biomarker discovery. On another end, disease-associated miRNomes may incline a patient’s response to treatment and toxicity. Here, we explored treatments for diseases in general that could be affected by FM and ME/CFS miRNomes, finding a long list of them, including treatments for lymphoma, a type of cancer affecting ME/CFS patients at a higher rate than healthy population. We conclude that FM and ME/CFS miRNomes could help refine pharmacogenomic/pharmacoepigenomic analysis to elevate future personalized medicine and precision medicine programs in the clinic.

scholarly journals Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking back on Treatments

2019 ◽  
Author(s):  
Eloy Almenar-Pérez ◽  
Teresa Sánchez-Fito ◽  
Tamara Ovejero ◽  
Lubov Nathanson ◽  
Elisa Oltra
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Biomarker Discovery ◽  
Drug Effects ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Response To Treatment ◽  
Molecular Diagnostic ◽  
Unknown Etiology ◽  
Healthy Population ◽  
Fatigue Syndrome

Fibromyalgia (FM) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are diseases of unknown etiology presenting complex and often overlapping symptomatology. Despite promising advances on the study of miRNomes of these diseases, no validated molecular diagnostic biomarker yet exists. Since FM and ME/CFS patient treatments commonly include polypharmacy it is of concern that biomarker miRNAs are masked by drug interactions. Aiming at discriminating between drug-effects and true disease-associated differential miRNA expression, we evaluated the potential impact of commonly prescribed drugs on disease miRNomes, as reported by the literature. By using the web search tools SM2miR, Pharmaco-miR and repoDB, we found a list of commonly prescribed drugs that impact on FM and ME/CFS miRNomes and therefore could be interfering in the process of biomarker discovery. On another end, disease-associated miRNomes may incline patient´s response to treatment and toxicity. Here, we explored treatments for diseases in general that could be affected by FM and ME/CFS miRNomes finding a long list of them, including treatments for lymphoma, a type of cancer affecting ME/CFS patients at a higher rate than healthy population. We conclude that FM and ME/CFS miRNomes could help refine pharmacogenomic/pharmacoepigenomic analysis to elevate future personalized medicine and precision medicine programs in the clinic.

Sign in / Sign up

Export Citation Format

Share Document