Review article: Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?, 2018, Newberry et al

Andy

Retired committee member
Abstract
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development.

However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases.

Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.
http://www.clinsci.org/content/132/5/523
 
Does the microbiome contribute causally to any syndrome?

A couple of recent studies have shown similar reductions in the micorbiome's diversity in ME/CFS as is seen in Chron's disease and chronic ulcerative colitis (the two major types of "inflammatory bowel disease," or IBD). I believe whether that reduction in diversity is a cause or a consequence of those diseases is currently unknown. Understanding what's behind the reduced diversity in the microbiome of those diseases and ME/CFS, however, might provide insights into causation and/or treatment.

ETA:
It's kind of interesting that one of the primary drugs used to treat Chron's disease and chronic ulcerative colitis, i.e. azulfidine (sulfasalazine), is also used to treat rheumatoid arthritis.
 
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A couple of recent studies have shown similar reductions in the micorbiome's diversity in ME/CFS as is seen in Chron's disease and chronic ulcerative colitis (the two major types of "inflammatory bowel disease," or IBD). I believe whether that reduction in diversity is a cause or a consequence of those diseases is currently unknown. Understanding what's behind the reduced diversity in the microbiome of those diseases and ME/CFS, however, might provide insights into causation and/or treatment.

The problem is that the effect on the GI tract in both cases is likely to affect the microbiome and while IBS is common in ME/CFS there doesn't appear to be any distinguishing underlying pathology of the GI tract.

If they could point to X disease where a reduction in microbiome diversity results in Y symptoms where fatigue (exertion intolerance or whatever) is prominent then there might be a stronger case to suspect similar mechanisms in ME/CFS.
 
I only read your quote @Andy but this strikes me as a fishing expedition.
That said without a proven disease mechanism i suppose its hard to do much better.
 
On balance I dont think the microbiome is the answer to the ME CFIDS I have because it is imho evidently an interaction between human infecting viruses and my immune system, because ME onset was synchronous with a marked infection for me but I do think that standardisation and replication of studies is an important necessary discipline whatever science is being done.

Besides which you dont know unless you look and there may be a subtype of CFS the microbiome is relevant for, in which case, best to identify it so it can be considered in development of diagnostic criteria and subtyping.
 
It's the latest paper from the Quadram Institute (QI) Bioscience team at Norwich Research Park UK, hub of the Invest in ME Research Centre of Excellence for ME. They started their biomedical research programme (got underway Oct. 2013 with patient samples taken from 2014) with the gut because of its importance to the immune system. They're taking a strategic and collaborative approach to their investigations and this is why they highlight the need for study design to be consistent to allow statistical comparison between different microbiome studies.

This collaborative work is facilitated by the annual IiME Research Conference and particularly, the Biomedical Research into ME Colloquium.

I'm hoping that one of the students involved will have time to produce a lay summary of this paper for the IiME Research Blogs.

Previous blogs by IiMER-funded PhD students Katharine Seton (QI) and Fane Mensah (UCL) are here:
http://www.investinme.org/ce-research-blogs.shtml

A blog by former IiMER-funded medical student (now qualified medical doctor) Navena Navaneetharaja, on the team's first review paper in 2016, ' A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)?' is here: http://blogs.ifr.ac.uk/ghfs/2016/07/me-cfs-virome/

As part of the international collaboration, Navena spent three months at Cornell in Maureen Hanson's lab.

Just seen this tweeted by PhD candidate Katharine Seton...

 
This 2017 study from Columbia's Center for Infection and Immunity showed that differing levels of various gut bacteria (called "abnormal levels" in the press release) distinguished ME/CFS patients from healthy controls and also distinguished ME/CFS patients with IBS symptoms from those without IBS symptoms. [Prior studies have reported that the number of ME/CFS patients with IBS symptoms ranges from 30 to 90 percent.]

The differences in gut bacteria levels were strong enough to be "predictive" when it came to distinguishing ME/CFS patients with IBS symptoms from those without IBS symptoms, and the levels of another subset of bacteria "appeared to be predictive" of ME/CFS itself.

https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y

Highlights from the press release:
  • Levels of distinct intestinal bacterial species—Faecalibacterium, Roseburia, Dorea, Coprococcus, Clostridium, Ruminococcus, Coprobacillus—were strongly associated with ME/CFS; their combined relative abundance appeared to be predictive of diagnosis
  • Increased abundance of unclassified Alistipes and decreased Faecalibacterium were the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS
  • An analysis of bacterial metabolic pathways associated with disturbances in gut bacteria revealed distinct differences between ME/CFS and ME/CFS subgroups relative to healthy controls
  • In ME/CFS subgroups, symptom severity measures, including pain and fatigue, correlated with the abundance of distinct bacterial types and metabolic pathways
https://www.mailman.columbia.edu/pu...fatigue-syndrome-linked-imbalanced-microbiome
 
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