Research Roundup: ME/CFS Research Published 30 October – 5 November 2021

November 11, 2021

The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight the studies that have particularly caught our interest and follow these with the full list of publications together with their abstracts (summaries).


The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.

ME/CFS Research Published 30 October – 5 November 2021  

Twonew research studies on ME/CFS have been published and we have also included sixteenstudies on Long-COVID.   We have highlighted these two papers on ME/CFS below: 

The first paper (1) is a preprint and has not been peer-reviewed (see more information here), however this study on the microbiome in ME/CFS finds some significant differences with decreased gut microbial diversity and greater heterogeneity

This paper used 75 ME/CFS patients who have had ME/CFS under four years (classed in the paper as short-term) and 79 patients who have had the illness for over ten years (classed in the paper as long-term) as well as 79 healthy controls. The study used blood plasma and gut microbiota and performed biological analysis on multi different molecules, known as multi-omics (such as genomes, proteomes, transcriptomes, epigenomes, metabolomes, and microbiomes). This is the most comprehensive study to date in this field. 

To highlight some of the key findings in this paper, ME/CFS patients were found to have: 

  • Reduced gut microbiome diversity,  
  • Greater gut heterogeneity of microbes, 
  • Depletion of sphingomyelins in plasma (compound in cell membranes) 
  • Depletion of short chain fatty acids in plasma, 
  • ‘Short-term’ ME/CFS patients had more microbial dysbiosis (reduced microbial diversity), 
  • ‘Long-term’ ME/CFS patients had more severe phenotypic and metabolic abnormalities, 
  • Reduced gene-coding capacity of microbiomal butyrate biosynthesis (involved in the breakdown of polysaccharides like starch). 

The results from this study allowed the authors to distinguish between ‘short’, ‘long’ term ME/CFS and healthy controls. These results, may also help to establish a diagnostic test for ME/CFS. 

Results from this study can be further questioned as many people with ME/CFS change their diet, for example as a result of increasing food intolerances or the change in ability to cook decreasing food diversity. Therefore, it could be hard to directly attribute these changes to ME/CFS. The paper hasn’t answered the question, are microbiome changes causing ME/CFS or are these changes caused by patients being ill, especially considering the reduced microbial diversity in ‘short-term’ ME/CFS was seen to stabilise in people who had had the illness ‘long-term’. 

The second paper (2) is a review of already published papers (via systematic review and meta-analysis) on the Chinese massage technique ‘Tuina’. The authors conclude, while the technique can help to relieve fatigue, there is not currently enough evidence to say it is an affected method for treatment. 

There are quite a few interesting Long-COVID papers this week too. You may also be interested in reading in the long-COVID section:  

  • Paper one (1) which looks into mitochondrial function, 
  • Paper four (4) which looks at trapped inflammatory molecules concluding that microclots in blood plasma may be the cause of lasting symptoms, 
  • Paper twelve (12) which looks at POTS in long-COVID. 

ME/CFS Research References and Abstracts  

1. Multi-‘omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) 

Xiong RGunter CFleming EVernon SDBateman LUnutmaz DOh J 

bioRxiv; 2021. Preprint 


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system, debilitating disability manifesting as severe fatigue and post-exertional malaise.  

The chronic dysfunctions in ME/CFS are increasingly recognized as significant health factors with potential parallels with ‘long COVID’. However, the etiology of ME/CFS remains elusive with limited high-resolution human studies. In addition, reliable biomarker-based diagnostics have not been well-established, but may assist in disease classification, particularly during different temporal phases of the disease.  

Here, we performed deep multi-‘omics (shotgun metagenomics of gut microbiota and plasma metabolomics) and clinical phenotyping of healthy controls (n=79) vs. two cohorts of ME/CFS patients – those with short-term disease (<4 years, n=75), and patients with long-term disease (>10y, n=79).  

Overall, ME/CFS was characterized by reduced gut microbiome diversity and richness with high heterogeneity, and depletion of sphingomyelins and short-chain fatty acids in the plasma.  

We found significant differences when stratifying by cohort; short-term ME/CFS was associated with more microbial dysbiosis, but long-term ME/CFS was associated with markedly more severe phenotypic and metabolic abnormalities.  

We identified a reduction in the gene-coding capacity (and relative abundance of butyrate producers) of microbial butyrate biosynthesis together with a reduction in the plasma concentration of butyrate, especially in the short-term group.  

Global co-association and detailed gene pathway correlation analyses linking the microbiome and metabolome identified additional potential biological mechanisms underlying host-microbiome interactions in ME/CFS, including bile acids and benzoate pathways.  

Finally, we built multiple state-of-the-art classifiers to identify microbes, microbial gene pathways, metabolites, and clinical features that individually or together, were most able to differentiate short or long-term MECFS, or MECFS vs. healthy controls.  

Taken together, our study presents the highest resolution, multi-cohort and multi-‘omics analysis to date, providing an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS. 

2. The effects of traditional Chinese manual therapy (Tuina) for chronic fatigue syndrome- A protocol for systematic review and meta-analysis 

Ren J, He T, Zhou X, Wu Z, Kong L 

Medicine: November 05, 2021 – Volume 100 – Issue 44 – p e27700 


Background: Chronic fatigue syndrome (CFS) is a common disease and characterized by fatigue, exhaustion, heavy limbs, and dizziness. Tuina, as a traditional Chinese manual therapy, is usually used for CFS in China. Several studies have reported that Tuina can improve fatigue exhaustion, and dizziness of patients with CFS. However, the effects of Tuina for CFS still remain controversial. Therefore, the current systematic review and meta-analysis will be conducted to investigate the effects of Tuina in the management of CFS. 

Methods: The comprehensive electronic search of PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, Embase, Cochrane Library, Chinese Science Citation Database, Technology Periodical Database from their inception to October 2021 will be conducted. Randomized controlled trials of Tuina for CFS will be included in the review. Two independent reviewers will complete the study selection, data extraction, and the risk of bias. The meta-analysis will be conducted using the Review Manager Version 5.3 software. The heterogeneity will be assessed using the I2 statistic and Q statistic. The standardized mean difference and 95% confidence intervals will be calculated based on different heterogeneity. The subgroup analysis will be conducted based on the duration of treatment, age, gender, duration of CFS. Quality of evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation. 

Results: The current systematic review and meta-analysis will be to investigate the effects of Tuina in the management of CFS. 

Conclusion: The conclusion of this study will provide the evidence for the treatment of CFS in the future. It is expected that the conclusions drawn from this review will benefit patients, clinical practitioners and policy makers. 

Long-COVID Research References   

  1. SARS-CoV-2 and EBV; the cost of a second mitochondrial “whammy”? 
  1. Strategies to evaluate outcomes in long-COVID-19 and post-COVID survivors 
  1. COVID-19 and Long Covid: Organs Damage and Dysfunctions, and Implications for Clinical Course 
  1. Trapped Inflammatory Molecules Contribute to Long COVID 
  1. What are the recommendations for returning athletes who have experienced long term COVID-19 symptoms? 
  1. COVID-19: adrenal response and molecular mimicry 
  1. The Race to Understand Post-COVID-19 Conditions 
  1. Screening of a Small Number of Italian COVID-19 Syndrome Survivors by Means of the Fatigue Assessment Scale: Long Covid Prevalence and the Role of Gender 
  1. Neurological Presentations in Long COVID-19 Syndrome in Childhood: First Data from the Pediatric Long COVID-19 Outpatient Clinic Jena 
  1. Systemic corticosteroids for management of ‘long-COVID': an evaluation after 3 months of treatment 
  1. COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis 
  1. Management of Long-COVID Postural Orthostatic Tachycardia Syndrome With Enhanced External Counterpulsation 
  1. More on Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome 
  1. Long COVID risk – a signal to address sex hormones and women's health 
  1. Brain correlates of depression, post-traumatic distress, and inflammatory biomarkers in COVID-19 survivors: A multimodal magnetic resonance imaging study 
  1. Molecular Imaging Suggests Long-COVID Symptoms May Be Caused by Fatigue, Not Regional Brain Dysfunction hormones and  

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent



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