“We can now definitively say that there are identifiable physiological differences between people with CFS and those without.”
Since 2016 published research looking at differences in people with CFS and those without have been able to paint a much better picture of what the mechanism looks like. Both observational and mechanistic studies from multiple independent research groups have returned favourable results for identifying key markers that can help determine the flow and progression of CFS. We can now much better understand what is chronic fatigue based on 3 key studies outlined below:
Giloteaux et al. (2016) – In this study researchers profiled gut microbial diversity by sequencing genes from stool samples in 48 patients with CFS and 39 healthy controls. They also examined a set of inflammatory markers in blood from the same patients as a gauge of intestinal damage, gut permeability and internal oxidative and inflammatory stress. All patients with chronic fatigue had increased levels of gut permeability (leaky gut), increased levels of intestinal damage and increased levels of inflammatory and auto-immune activity associated with microbial translocation. Further to this they all had a reduced gut biodiversity measured by bacterial DNA count from fecal samples compared to healthy controls.
Summary: Patients with chronic fatigue have increased bacterial gut permeability, increased incidence of leaky gut and generic gut dysbiosis of the microbiome.
Montoya et al. (2017) – This study set out to determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration. Cytokines of 192 ME/CFS patients and 392 healthy controls were measured. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity. Of the 17 cytokines that correlated with severity, 13 are pro-inflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease
Summary: There is an immune dysfunctional component linked to the condition, with the severity of symptoms being directly related to the levels of inflammation and auto-immune inflammation. The worse the inflammation the worse the symptoms.
Blomberg et al. (2018) – This mechanistic evaluation demonstrated that CFS patients with a genetic predisposition and dysbiosis experienced a gradual development of B cell clones that were prone to auto-reactivity. A decisive infectious trigger may then lead to immunization against auto-antigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing post-exertional malaise (PEM) and ME/CFS, affecting both muscle and brain tissue.
Summary: In CFS there is an auto-immune and inflammatory interference on the energy production pathways of the body in the mitochondria. Increased metabolism (through exercise) can lead to increased oxidative stress and exacerbation of symptoms (post-exertional malaise – PEM). It is thought that the condition is triggered by a genetic predisposition, dysbiosis and an infectional trigger.
The above model represents a good fit for CFS and can be used to help explain many of the non-localised symptoms. Patients complain of extreme fatigue, muscle and/or joint pain, swollen glands, headaches, gastrointestinal (GI) symptoms, unrefreshing sleep and post-exertional tiredness without relief. The feeling of a low lying infection, swollen glands, GI upsets and weakened immunity can be explained by the mechanism of dysbiosis leading to increased gut permeation of biome bacteria and a responding continual low-level immune response. Left unchecked this type of infection can create an immunological dysfunction and possible auto-immunity causing disruption of the natural stress response via dysregulation the HPA axis (hypothalamus – pituitary – adrenals). Long-term adrenal dysfunction can explain other symptoms like sleep disruption, anxiety, feelings of burnout etc. While dysregulation of energy metabolism can lead to symptoms like brain fog, fatigue and post-exertional malaise (PEM).
The key questions surrounding this process are related to the triggers, i.e why does it happen? and also the step-wise progression, i.e how does it happen? Unfortunately as every body is different and no two people with chronic fatigue experience the exact same symptoms it is hard to create anything definitive as to the cause and progression. But the process itself is likely to follow the inflammatory cascade with 5 key steps:
Examples of possible initiators that can ‘spark’ the inflammatory cascade.
Dysregulation of the HPA axis causes adrenal dysfunction and chronic inflammation, exacerbating global symptoms.
Chronic inflammation, HPA dysregulation and immune dysfunction leads to interference of energy production, metabolism and PEM.
Following the inflammatory cascade we find a chicken or the egg situation where the tail of one leads to the mouth of the other. The initiation in the gut leads to the dysregulation in the brain and this in-turn returns to initiate more inflammation in the gut.
So regardless on the position a patient begins on the progression once in place the model displays a downward spiral that propagates it’s own demise. This seems to be the reason why people with CFS find it so difficult to recover as working on one aspect of health may be overridden by other multi-faceted dysfunctions pulling the person back into the downward spiral.
Either way the progression the gut leads to the brain and the brain leads to the gut creating a downward spiral of pathophysiology.
Many new studies have begun to unlock the once unknown physiology of chronic fatigue. There are still many questions to answer about the full details but we now have a much clearer model of what is going on than we had even 5 years ago. Understanding some of the key points and processes gives us the ability to focus our attention towards management and recovery plans.
Having personally recovered from chronic fatigue there are many things I wish I had known during my journey as the process could have been much more streamlined using a similar model as the one outlined above. Given no two people are the same and no two chronic fatigues are the same there is no ‘one size fits all’ but there is now at least a framework that can help narrow down opportunities to assist with recovery. I personally believe that recovery is possible for anyone given the right health map, plan, knowledge and mindset. To read more see my journey here and subscribe for more future updates and information on how to create your own health map for recovery.
Written by Dr Corin Storkey Founder and Director of Seleno Health. www.selenohealth.com
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