08. Oct 2020

Margit Koudelka

Does a sick intestine make you tired?

The mystery of chronic fatigue

Are you often tired and exhausted, even after the smallest task? You may be suffering from a disease that is still a riddle to scientists: Chronic fatigue syndrome. This disease has many other symptoms that can severely reduce your quality of life. Much time often goes by until a diagnosis is made and, until now, a cure is not possible. Scientists suspect that the problem may originate within the intestines and current studies give the affected a ray of hope.

Chronic fatigue syndrome goes by many names, but it is mainly known as CFS or myalgic encephalomyelitis (ME). Specialists and experts use the abbreviation ME/CFS when referring to the disease. Worldwide, roughly 0,2-0,9% of the population suffers from this syndrome, with 300.000 cases in Germany and about 25.000 in Austria. ME/CFS occurs in all age groups, even in children and teenagers. Women are affected more than men (ration of 3:1). Although the World Health Organisation already classified it as a neurological disease back in 1969, many don’t take this disease seriously and it is often not recognised as a “proper disease”.

Persistent fatigue – is the gut to blame?

The disease can be compared to an empty battery. Simple tasks such as teeth brushing or cooking can leave a person exhausted. Afterwards, they need to rest“, explains Mag. Dr Monika Riederer, a lecturer at the Institute for Biomedical Analytics at the JOANNEUM University for Applied Sciences, Graz. This intolerance towards stress and exercise is one of the most telling signs of chronic fatigue syndrome. This disease is also accompanied by many other symptoms, as Dr Riederer explains: “ME/CFS includes a plethora of anomalies. They affect the immune and nervous systems as wells as the hormonal system, the cardiovascular system and our bodies’ entire metabolism.” The affected suffer from a severe sense of weakness, muscle pain, flu-like symptoms, fitful sleep and general poor health (for details, see Info-box 1 “symptoms”). These symptoms are exacerbated after the merest of physical or mental exertions – specialists call this “post-exertional malaise”. “Outsiders may think these symptoms aren’t so bad. However, patients suffer to such an extent that 25% can’t leave their homes and more than 60% are unable to work“, clarifies Dr Riederer about the severe consequences of chronic fatigue syndrome.

Diagnosis: Chronic Fatigue Syndrome

The pathogenesis – i.e. the development of the disease – is still largely unexplained. “We know that ME/CFS often begins after a severe acute infection. Possible causes may include autoimmune diseases, a hyperactive immune system, metabolism disorders (so-called hypometabolic syndrome) and disorders of the autonomous nervous system. Even viral infections, e.g. Epstein Barr Virus, could trigger the disease”, explains the expert. Since many causes are still unknown, and since the symptoms could also apply to several other diseases, the road to the right diagnosis is often long and gruelling for the affected. Currently, there are no validated lab or instrumental tests to make an accurate diagnosis. That is why a close analysis of the patient history and the symptoms is essential. Firstly, other diseases that cause similar states of exhaustion have to be excluded. These include diseases such as multiple sclerosis, tumours, thyroid disorders and anaemias. The attending physician uses a so-called criteria catalogue for the diagnosis. Here, the type and duration of the complaints are determined to correctly diagnose ME/CFS (see Info-box 2 “diagnosis criteria”).

Symptoms of Chronic Fatigue Syndrome

  • Post-exertional malaise: Increase in symptoms after physical or mental exertion.
  • Chronic fatigue: Excessive exhaustion and weakness.
  • Orthostatic intolerance: The inability of the body to adapt the circulation to a standing position. This manifests itself through weakness, dizziness, palpitations, high or low blood pressure, paleness and shortness of breath.
  • Neurocognitive symptoms: Concentration disorders, difficulty finding words, memory problems and “brain fog” (the brain feels foggy).
  • Neurological symptoms: Hypersensibility towards lights, sounds and smells as well as ataxia (movement coordination disorder).
  • Increased susceptibility towards infections: More infections that last longer than usual. Especially infections in the upper airways.
  • Sleeping problems: Difficulties remaining asleep. In other words, light and fitful sleep. Patients often suffer from a reversed day-night rhythm.
  • Myalgic complaints: Muscle pain after minimal exertion. In severe cases, patients suffer from fasciculations (muscle twitching) and recurring cramps.
  • Headaches: They resemble a migraine and can last for several days.
  • Visual disorders: Blurry vision, accommodation disorders (eye-lens can’t focus properly) and tunnel vision.

Are there any therapies for chronic fatigue syndrome?

There is currently no approved treatment to cure ME/CFS. There are no specific drugs and, consequently, no cure. Treatment is only symptom-oriented, and patients usually receive painkillers, sleeping aids and antidepressants. Furthermore, patients are supported by so-called pacing strategies – in other words, this method helps patients learn how to cope with their reduced levels of energy.  ME/CFS has been the subject of multiple clinical studies. Since the disease is so complex and multi-layered, the therapeutic approaches that were analysed in the studies were also very heterogeneous. The pharma sector also studied psychotropic drugs, cortisol and drugs that had an impact on the immune system (immune modulators) and mitochondria. Mitochondria are the powerhouses of the cells and transform food into ATP (adenosine triphosphate), the bodies energy currency. Outside of the pharma sector, other treatment methods were examined more closely. These included cognitive behaviour therapy, movement therapy and a change in diet. Sadly, only very few of these approaches were effective. “Only 8 out of 55 randomised, controlled clinical studies showed any signs of success, mainly the non-pharmacological methods. They significantly improved the symptoms of the patients”, reports Dr Riederer. All in all, the behaviour therapy, the change in diet and the massages showed the most promise. Furthermore, one mitochondrial drug and two immune-modulating drugs showed positive results.

Does an altered intestinal flora make you tired?

“If you take a closer look at the study results, it becomes clear that even though there were single positive effects, it wasn’t enough to treat even a part of the disease. Instead, treatment should focus on several areas”, explains the biochemist. As such, in her research she focusses on whether the patients can be diagnosed through biomarkers and whether therapeutic success can be measured. Biomarkers are substances or changes that can be quantifiably measured. They allow us to draw conclusions about the health or disease of a person and how successful an action or treatment is. A practical example of a diagnostic biomarker is the blood pressure measurement in cardiovascular diseases. However, there are currently no biomarkers for ME/CFS that have been corroborated by studies. Nevertheless, there are three interesting clues:

  • In comparison to healthy people, the cytokine profile of ME/CFS patients is often altered. Cytokines are certain proteins that transmit signals between cells. They also help the growth and specialisation of cells and even hint towards inflammatory reactions.
  • The marker for oxidative stress is significantly higher in patients with ME/CFS. Simply put, oxidative stress refers to an impaired reparation and detoxification of the cells in our bodies. This leads to damage in and on the cells.
  • Even the intestinal microbiome, the entirety of all the inhabiting microorganisms in our intestines, shows certain changes. In other words, the biodiversity of the intestines is lower than in that of healthy individuals. Additionally, ME/CFS patients have more pro-inflammatory intestinal bacteria than anti-inflammatory microorganisms.

“This suggests that – as with many other diseases – there is a connection between ME/CFS and the intestinal flora, and that, consequently, the brain-gut-axis also plays a role”, analyses Dr Riederer. She even expands on this statement with another component: She refers to the “brain-gut-immune-system-axis” for several reasons. Firstly, the immune system is the most important common factor in these heterogeneous diseases. Secondly, the immune system appears to be chronically overactivated. And thirdly, 80% of the immune cells in the body can be found in the intestines, and the intestinal flora is a major part of the human defence system.

Diagnostic help in the form of microbiome analysis?

ME/CFS patients are in a chronic, hypometabolic state. It’s like a “metabolic hibernation”. The bodies altered reaction towards oxidative stress also hints towards roots of the disease lying in the microbiome. Initial studies about this disease allow such a conclusion. “Even though these studies weren’t completely homogeneous, the scientists were able to filter out 8 bacteria species that could indicate whether someone has ME/CFS or not”, reports Dr Riederer. Therefore, certain bacteria species could act as biomarkers which would greatly facilitate and accelerate the diagnosis of chronic fatigue syndrome.
Besides an altered microbiome, most of the affected also show signs of an irritable colon and other intestinal complaints. Blood tests revealed that serum levels of the plasma-intestinal-fatty-acid-binding-protein (IFABP) were increased in patients with ME/CFS. This special protein is an important biomarker that points towards a “leaky gut” or leaky intestinal barrier. A leaky gut allows harmful bacteria and other unwanted substances to enter all corners of the body.

Intestinal bacteria: a beacon of hope

What do these data and these hints now mean for the diagnosis and treatment of ME/CFS? One workgroup was able to diagnose ME/CFS in 82,93% of patients with the data from the survey of the bacterial diversity. The clues are mounting that an impaired intestinal flora could really be one of the causes of chronic fatigue syndrome. This could lead to new therapeutic approaches, such as special diets or the targeted use of probiotics with specifically combined bacterial strains. Three small studies were already able to confirm that probiotics have a positive effect on the general wellbeing of the patients and inflammatory parameters associated with chronic fatigue syndrome – a ray of hope for all of the affected.

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