scholarly journals A Cartography of Differential Gene Methylation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Different Network Roles in the Protein-Protein Interactions Network Play Different, Biologically Relevant, Roles

2021 ◽  
Author(s):  
Aurelia Wilberforce ◽  
Giulio Valentino Dalla Riva
Keyword(s):  
Dna Methylation ◽  
Chronic Fatigue Syndrome ◽  
Sample Size ◽  
Protein Interactions ◽  
Small Sample Size ◽  
Chronic Fatigue ◽  
Small Sample ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Differentially Methylated Genes

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS), is a debilitating illness characterised by severe fatigue and associated with immune dysfunction. Previous studies of DNA methylation (epigenetic changes that can affect the gene transcription) have found evidence of changes in immune cells for ME/CFS. However these studies have been limited by their small sample size, precluding the ability to detect changes to methylation of smaller magnitude. Therefore, to achieve a larger sample size and detect small changes to DNA methylation, we aggregate three comparable datasets and analyse them in unison. We find 10,824 differentially methylated genes, with a very small average change. We then turn our attention to the network structure of the Protein-Protein interaction, which we built from the currently known interactions of relevant proteins, and localising the network cartography framework, we identify 184 hub genes. A distinct structuring emerges, with different hub types playing differing, meaningful, biological roles. Supporting previous theories about ME/CFS, Gene ontology enrichment analysis of these hubs reveal that they are involved in immune system processes, including response to TGF-β and LPS, as well as mitochondrial functioning. We also show that dopaminergic signalling may potentially contribute to immune pathology in ME/CFS. Our results demonstrate the potentiality of network cartographic approaches in shedding light on the epigenetic contribution to the immune dysregulation of ME/CFS.

Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome

Epigenomics ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 539-557 ◽  
Author(s):  
Wilfred C de Vega ◽  
Lauren Erdman ◽  
Suzanne D Vernon ◽  
Anna Goldenberg ◽  
Patrick O McGowan
Keyword(s):  
Dna Methylation ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome

scholarly journals Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0201066 ◽  
Author(s):  
Malav S. Trivedi ◽  
Elisa Oltra ◽  
Leonor Sarria ◽  
Natasha Rose ◽  
Vladimir Beljanski ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Methylation Patterns

scholarly journals Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 652
Author(s):  
Samaneh Khanpour Khanpour Ardestani ◽  
Mohammad Karkhaneh ◽  
Eleanor Stein ◽  
Salima Punja ◽  
Daniela R. Junqueira ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Fatigue Syndrome ◽  
Signs And Symptoms ◽  
Chronic Fatigue ◽  
Small Sample ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Fatigue Severity ◽  
Anxiety Depression

Background and Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic condition distinguished by disabling fatigue associated with post-exertional malaise, as well as changes to sleep, autonomic functioning, and cognition. Mind-body interventions (MBIs) utilize the ongoing interaction between the mind and body to improve health and wellbeing. Purpose: To systematically review studies using MBIs for the treatment of ME/CFS symptoms. Materials and Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL were searched (inception to September 2020). Interventional studies on adults diagnosed with ME/CFS, using one of the MBIs in comparison with any placebo, standard of care treatment or waitlist control, and measuring outcomes relevant to the signs and symptoms of ME/CFS and quality of life were assessed for inclusion. Characteristics and findings of the included studies were summarized using a descriptive approach. Results: 12 out of 382 retrieved references were included. Seven studies were randomized controlled trials (RCTs) with one including three reports (1 RCT, 2 single-arms); others were single-arm trials. Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation, Qigong, cognitive-behavioral stress management, acceptance and commitment therapy and isometric yoga. The outcomes measured most often were fatigue severity, anxiety/depression, and quality of life. Fatigue severity and symptoms of anxiety/depression were improved in nine and eight studies respectively, and three studies found that MBIs improved quality of life. Conclusions: Fatigue severity, anxiety/depression and physical and mental functioning were shown to be improved in patients receiving MBIs. However, small sample sizes, heterogeneous diagnostic criteria, and a high risk of bias may challenge this result. Further research using standardized outcomes would help advance the field.

scholarly journals Deficient Butyrate-Producing Capacity in the Gut Microbiome of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients is Associated with Fatigue Symptoms

2021 ◽  
Author(s):  
Cheng Guo ◽  
Xiaoyu Che ◽  
Thomas Briese ◽  
Orchid Allicock ◽  
Rachel A. Yates ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Gut Microbiome ◽  
Symptom Severity ◽  
Chronic Fatigue ◽  
The United States ◽  
Small Sample ◽  
Myalgic Encephalomyelitis ◽  
Healthy Controls ◽  
Shotgun Metagenomics ◽  
Fatigue Syndrome

Abstract Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, debilitating disease of unknown cause for which there is no specific therapy. Patients suffering from ME/CFS commonly experience persistent fatigue, post-exertional malaise, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever and irritable bowel syndrome (IBS). Recent evidence implicates gut microbiome dysbiosis in ME/CFS. However, most prior studies are limited by small sample size, differences in clinical criteria used to define cases, limited geographic sampling, reliance on bacterial culture or 16S rRNA gene sequencing, or insufficient consideration of confounding factors that may influence microbiome composition. In the present study, we evaluated the fecal microbiome in the largest prospective, case-control study to date (n=106 cases, n=91 healthy controls), involving subjects from geographically diverse communities across the United States. Results: Using shotgun metagenomics and qPCR and rigorous statistical analyses that controlled for important covariates, we identified decreased relative abundance and quantity of Faecalibacterium , Roseburia , and Eubacterium species and increased bacterial load in feces of subjects with ME/CFS. These bacterial taxa play an important role in the production of butyrate, a multifunctional bacterial metabolite that promotes human health by regulating energy metabolism, inflammation, and intestinal barrier function. Functional metagenomic and qPCR analyses were consistent with a deficient microbial capacity to produce butyrate along the acetyl-CoA pathway in ME/CFS. Metabolomic analyses of short-chain fatty acids (SCFAs) confirmed that fecal butyrate concentration was significantly reduced in ME/CFS. Further, we found that the degree of deficiency in butyrate-producing bacteria correlated with fatigue symptom severity among ME/CFS subjects. Finally, we provide evidence that IBS comorbidity is an important covariate to consider in studies investigating the microbiome of ME/CFS subjects, as differences in microbiota alpha diversity, some bacterial taxa, and propionate were uniquely associated with self-reported IBS diagnosis. Conclusions: Our findings indicate that there is a core deficit in the butyrate-producing capacity of the gut microbiome in ME/CFS subjects compared to healthy controls. The relationships we observed among symptom severity and these gut microbiome disturbances may be suggestive of a pathomechanistic linkage, however, additional research is warranted to establish any causal relationship. These findings provide support for clinical trials that explore the utility of dietary, probiotic and prebiotic interventions to boost colonic butyrate production in ME/CFS.

scholarly journals Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents

2017 ◽  
Vol 102 (6) ◽  
pp. 522-528 ◽  
Author(s):  
Tom Norris ◽  
Simon M Collin ◽  
Kate Tilling ◽  
Roberto Nuevo ◽  
Stephen A Stansfeld ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Small Sample ◽  
Myalgic Encephalomyelitis ◽  
Natural Course ◽  
Fatigue Syndrome ◽  
Parents And Children ◽  
Unbiased Estimates ◽  
Small Sample Sizes

ObjectiveLittle is known about persistence of or recovery from chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adolescents. Previous studies have small sample sizes, short follow-up or have focused on fatigue rather than CFS/ME or, equivalently, chronic fatigue, which is disabling. This work aimed to describe the epidemiology and natural course of CFS/ME in adolescents aged 13–18 years.DesignLongitudinal follow-up of adolescents enrolled in the Avon Longitudinal Study of Parents and Children.SettingAvon, UK.ParticipantsWe identified adolescents who had disabling fatigue of >6 months duration without a known cause at ages 13, 16 and 18 years. We use the term ‘chronic disabling fatigue’ (CDF) because CFS/ME was not verified by clinical diagnosis. We used multiple imputation to obtain unbiased estimates of prevalence and persistence.ResultsThe estimated prevalence of CDF was 1.47% (95% CI 1.05% to 1.89%) at age 13, 2.22% (1.67% to 2.78%) at age 16 and 2.99% (2.24% to 3.75%) at age 18. Among adolescents with CDF of 6 months duration at 13 years 75.3% (64.0% to 86.6%) were not classified as such at age 16. Similar change was observed between 16 and 18 years (75.0% (62.8% to 87.2%)). Of those with CDF at age 13, 8.02% (0.61% to 15.4%) presented with CDF throughout the duration of adolescence.ConclusionsThe prevalence of CDF lasting 6 months or longer (a proxy for clinically diagnosed CFS/ME) increases from 13 to 18 years. However, persistent CDF is rare in adolescents, with approximately 75% recovering after 2–3 years.

scholarly journals Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
A. M. Helliwell ◽  
E. C. Sweetman ◽  
P. A. Stockwell ◽  
C. D. Edgar ◽  
A. Chatterjee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Pathway Enrichment Analysis ◽  
Healthy Controls ◽  
Sequencing Data ◽  
Peripheral Blood Mononuclear ◽  
Fatigue Syndrome ◽  
Array Technology

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a lifelong debilitating disease with a complex pathology not yet clearly defined. Susceptibility to ME/CFS involves genetic predisposition and exposure to environmental factors, suggesting an epigenetic association. Epigenetic studies with other ME/CFS cohorts have used array-based technology to identify differentially methylated individual sites. Changes in RNA quantities and protein abundance have been documented in our previous investigations with the same ME/CFS cohort used for this study. Results DNA from a well-characterised New Zealand cohort of 10 ME/CFS patients and 10 age-/sex-matched healthy controls was isolated from peripheral blood mononuclear (PBMC) cells, and used to generate reduced genome-scale DNA methylation maps using reduced representation bisulphite sequencing (RRBS). The sequencing data were analysed utilising the DMAP analysis pipeline to identify differentially methylated fragments, and the MethylKit pipeline was used to quantify methylation differences at individual CpG sites. DMAP identified 76 differentially methylated fragments and Methylkit identified 394 differentially methylated cytosines that included both hyper- and hypo-methylation. Four clusters were identified where differentially methylated DNA fragments overlapped with or were within close proximity to multiple differentially methylated individual cytosines. These clusters identified regulatory regions for 17 protein encoding genes related to metabolic and immune activity. Analysis of differentially methylated gene bodies (exons/introns) identified 122 unique genes. Comparison with other studies on PBMCs from ME/CFS patients and controls with array technology showed 59% of the genes identified in this study were also found in one or more of these studies. Functional pathway enrichment analysis identified 30 associated pathways. These included immune, metabolic and neurological-related functions differentially regulated in ME/CFS patients compared to the matched healthy controls. Conclusions Major differences were identified in the DNA methylation patterns of ME/CFS patients that clearly distinguished them from the healthy controls. Over half found in gene bodies with RRBS in this study had been identified in other ME/CFS studies using the same cells but with array technology. Within the enriched functional immune, metabolic and neurological pathways, a number of enriched neurotransmitter and neuropeptide reactome pathways highlighted a disturbed neurological pathophysiology within the patient group.

scholarly journals Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paula I. Metselaar ◽  
Lucero Mendoza-Maldonado ◽  
Andrew Yung Fong Li Yim ◽  
Ilias Abarkan ◽  
Peter Henneman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Feature Selection ◽  
Chronic Fatigue Syndrome ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Methylation Data ◽  
Peripheral Blood Mononuclear ◽  
Fatigue Syndrome

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder characterized by disabling fatigue. Several studies have sought to identify diagnostic biomarkers, with varying results. Here, we innovate this process by combining both mRNA expression and DNA methylation data. We performed recursive ensemble feature selection (REFS) on publicly available mRNA expression data in peripheral blood mononuclear cells (PBMCs) of 93 ME/CFS patients and 25 healthy controls, and found a signature of 23 genes capable of distinguishing cases and controls. REFS highly outperformed other methods, with an AUC of 0.92. We validated the results on a different platform (AUC of 0.95) and in DNA methylation data obtained from four public studies on ME/CFS (99 patients and 50 controls), identifying 48 gene-associated CpGs that predicted disease status as well (AUC of 0.97). Finally, ten of the 23 genes could be interpreted in the context of the derailed immune system of ME/CFS.

scholarly journals Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Major Impact on Lives of Both Patients and Family Members

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 43
Author(s):  
Esme Brittain ◽  
Nina Muirhead ◽  
Andrew Y. Finlay ◽  
Jui Vyas
Keyword(s):  
Quality Of Life ◽  
Chronic Fatigue Syndrome ◽  
Physical Health ◽  
Family Members ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
World Health ◽  
Life Questionnaire ◽  
Fatigue Syndrome

Background and objectives: To explore the impacts that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has on the patient and their family members using the WHOQOL-BREF (Abbreviated World Health Organisation Quality of Life questionnaire) and FROM-16 (Family Reported Outcome Measure-16) quality of life assessments. Materials and Methods: A quantitative research study using postal questionnaires was conducted. A total of 39 adult volunteers expressed an interest in participating in the study: 24 returned appropriately completed questionnaires. Patients with ME/CFS completed the WHOQOL-BREF and up to four of their family members completed the FROM-16 questionnaire. Results: ME/CFS negatively affects the quality of life of the patient (median scores WHOQOL-BREF: Physical health = 19, Psychological = 44, Social relationships = 37.5, Environment = 56, n = 24) and their family members’ quality of life (FROM-16: Emotional = 9.5, Personal and social = 11.5, Overall = 20.5, n = 42). There was a significant correlation between the patient’s reported quality of life scores and their family members’ mean FROM-16 total scores. Conclusions: This study identifies the major impact that having an adult family member with ME/CFS has on the lives of partners and of other family members. Quality of life of ME/CFS patients was reduced most by physical health compared to the other domains. Quality of life of family members was particularly impacted by worry, family activities, frustration and sadness. This highlights the importance of measuring the impact on the lives of family members using tools such as the FROM-16 in the ME/CFS clinical encounter and ensuring appropriate support is widely available to family members.

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