Answers to ME/CFS May Lie Within the Gut

11 Jul 2016 --- Researchers on the Norwich Research Park have published a review of evidence for a role of the gut microbiota and virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Commonly presenting with hugely diverse and debilitating symptoms including post-exertional tiredness, unrefreshing sleep, concentration problems and widespread pain, ME/CFS is very difficult to diagnose and treat. 

The disease affects around 250,000 people in the UK and with an average age of 33, patients are often affected at a highly demanding time in life. Direct and indirect economic costs are estimated in the USA to be US$20 billion annually. The severity of symptoms varies. Around 25% of sufferers will be classed as disabled; often bed bound at some point in their lives with periods of relapse and remission common and only 6% returning to full health.

The detailed review, published in The Journal of Clinical Medicine, examines mounting evidence pointing towards an infectious and autoimmune basis for ME/CFS, with emphasis placed on the impact of the intestinal microbiota and virome, the bacterial and viral communities resident within our gut. 

The review was written by medical students Navena Navaneetharaja and Verity Griffiths, with Professor Simon Carding and Professor Tom Wileman from the University of East Anglia Norwich Medical School and Institute of Food Research, all based at the Norwich Research Park.

The gut, given its continued exposure to microbes, is an important location for autoimmune activity which could cause chronic disease if exposure becomes uncontrolled. Studies using sterile, germ-free mice models for inflammatory bowel disease, autoimmune arthritis and Type 1 diabetes showed that the animals have reduced severity/incidence of these conditions, possibly indicative of the microbiota as a trigger. 

No similar models have been developed for ME/CFS, but the review cites several independent studies as evidence, linking the abnormal movement of gut bacteria across the intestinal epithelial barrier to increased systemic inflammatory disease activity – so-called “leaky gut syndrome,” highlighting the importance of how the microbiota could become exposed to the host immune system.

The co-existence of ME/CFS and gastrointestinal symptoms is well documented with one study reporting that 92% of ME/CFS patients have co-existent irritable bowel syndrome. Significantly higher levels of Enterococcus and Streptococcus and lower levels of Bifidobacteria bacterial species has been reported in ME/CFS patients with 77% of them having some form of bacterial overgrowth. But it is too early to say if specific ME/CFS microbiota signatures exist. Data have so far lacked consistency but changes in intestinal balance (dysbiosis) could play a key role in ME/CFS development.
Particles from ME/CFS patient showing filamentous bacteriophages Particles from ME/CFS patient showing bacteriophages

The Norwich Research Park has a concentration of interdisciplinary researchers studying the microbiota, including the authors of this review. The human microbiota is often described by its bacterial populations, but it is much more complex and includes many other microorganisms, in particular viruses. With both viruses and the microbiota being implicated in ME/CFS, the review advocates a pronounced move of attention from the bacterial to the viral population of the intestine, particularly in relation to bacteriophages, viruses that infect bacteria. Whilst virus detection and identification is currently difficult, the virome is considered more stable and personal than our resident bacterial communities potentially pointing towards a specific virome profile for ME/CFS patients.

If the detailed research efforts can be accelerated and conducted in a co-ordinated fashion, it will support the development of therapeutics to address and alleviate the diverse range of incapacitating symptoms of ME/CFS, and will then ultimately provide much hope in moving towards prevention of a disease ignored for too long.