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January 10, 2017

Sara Adaes ›  

Could Chronic Fatigue Syndrome Start in the Gut?

Chronic fatigue syndrome (CFS), aka myalgic encephalomyelitis, is a highly disabling and complex condition that still remains very mysterious. According to the World Health Organization, an estimated 1.69% of the world population may be affected by CFS. The set of symptoms that characterise it have been described repeatedly since the 19th century, but given the difficulty in establishing a diagnosis, it wasn’t until 1988 that the term “chronic fatigue syndrome” was coined. Its causes are still unknown, although evidence suggests that chronic low-grade inflammation is one factor. Further, the gut microbiome is helping us paint a clearer picture.

Note that CFS is different to Adrenal Fatigue:

Adrenal Fatigue is a condition that is not recognised by the medical community wherein chronic fatigue is attributed to an exhaustion of the adrenal glands leading to an inability to produce sufficient quantities of hormones, particularly cortisol, due to chronic stress or infections.


CFS’s main characteristic is the unexplained, persistent or relapsing debilitating physical and mental fatigue that it causes.

Simple daily activities that require any effort quickly lead to exhaustion, from which it may take a long time to recover. Memory, concentration and sleep are affected. There may be headaches, joint pain, muscle pain, sore throat, and tender lymph nodes. It’s a lot to cope with and because of the commonality of the symptoms with other ailments, diagnosis becomes tricky.

The type and severity of symptoms vary widely from one patient to another, but they are always highly debilitating - it has a huge impact on quality of life and it substantially interferes with daily routines. CFS has no standard treatments - pharmacological approaches to its treatment have only shown, at best, moderate efficacy.

Chronic Fatigue Syndrome and the gut 


What causes it?

The most intriguing aspect of CFS is the fact that its causes are still unknown. Over the years, CFS has been attributed to infection, toxins, immune dysfunction, sleeping disorders, endocrine dysfunctions, metabolic dysfunctions, or neurological, emotional and psychiatric factors; models integrating all of these factors have also been proposed. However, none have been confirmed.

The fact is that CFS affects many physiological systems (e.g. nervous, endocrine, immune), and manifests itself both at a physical and a cognitive level. So, it seems that whatever triggers CFS has the power to turn it into a systemic disease, affecting the whole body.


Does chronic low-grade inflammation contribute to CFS?

Many of CFS’s symptoms are actually characteristic of inflammatory diseases. In fact, markers of general inflammation have been found in the blood of CFS patients, and dysfunctions of the immune system are often reported for this disease. Fatigue is a very common symptom of inflammation, and patients with inflammatory conditions often report both physical and mental fatigue.

There are many chronic conditions driven by a state of chronic low-grade inflammation. This chronic inflammatory state can underlie autoimmune diseases, neurodegenerative conditions, metabolic disorders, cardiovascular diseases… It can cause fatigue, decreased appetite, impaired sleep, concentration deficits, depression, mild cognitive impairment, pain… Sound familiar?

The hypothesis that inflammation plays a key role in CFS is not that far-fetched. Actually, research has also shown that CFS is indeed characterised by a low-grade inflammatory state. It was demonstrated that there are increased levels of inflammatory mediators that correlate with most of CFS’s symptoms, including fatigue, sadness, concentration difficulties, or failing memory, for example.

Interestingly, a recent study analysed the gut microbial profile of CFS patients and showed that their gastrointestinal tract is a pro-inflammatory environment which can potentially cause damage to the intestinal walls. This stands in line with other studies which have described a disruption of the intestinal mucosal barrier in CFS patients. This increased intestinal permeability may allow bacteria to translocate and invade the intestinal wall and trigger an immune response by releasing pro-inflammatory molecules and endotoxins into the bloodstream. This could create the state of chronic low-grade inflammation, explaining many of the symptoms observed in CFS.

CFS patients commonly show altered immune cell levels in the blood and in cerebrospinal fluid, the fluid found in the brain and spinal cord. Lipopolysaccharides (LPS), which are toxic molecules produced by a subset of gut bacteria, have been found in the blood of CFS patients. This is most likely due to the translocation of microbes through the damaged intestinal walls occurring as a consequence of the pro-inflammatory environment. LPS can produce strong immune responses in animals, including humans, and this could explain the immunological symptoms observed in CFS.

So, what this tells us is that in CFS patients there are generalised inflammatory and immune processes that can be caused by an inflamed gut.

Chronic Fatigue Syndrome and Gut Inflammation

Could the gut microbiota be to blame?

An interesting fact about CFS is that many patients report gastrointestinal symptoms, even though these are not part of the diagnostic criteria for the disease. This has motivated a number of studies on a possible role of the gut microbiota on the development of CFS.

A few studies have indeed shown evidence of an altered bacterial content on the gut of CFS patients. The study mentioned above, which investigated the bacterial diversity and composition of the gut of CFS patients in comparison to healthy subjects, found indications of an altered bacterial content which actually matches the bacterial profile of inflammatory bowel diseases.

Changes similar to those found in irritable bowel syndrome (IBS) were also determined. This is noteworthy because CFS is very common among people with IBS. IBS leads to a disruption of the intestinal barrier and to a state of chronic low-grade inflammation. It is possible that a similar mechanism occurs in CFS.

This could actually also explain the neurological and emotional symptoms of CFS. Even though the effect of the gut-brain axis in the development of CFS’s neurological symptoms has not been investigated, assuming that it plays a role is not a wild guess. It does fit the pattern of other diseases whose cognitive and psychiatric symptoms have been attributed to an altered intestinal flora.

In IBS, the microbiota-gut-brain axis is also increasingly regarded as the driver of cognitive and psychiatric symptoms. A similar effect may occur in CFS, even when patients do not develop IBS. The fact that gastrointestinal symptoms are recurrent make it a likely hypothesis.

Gut Microbiota and CFS Chronic Fatigue Syndrome

The gut microbiota can impact the brain in many ways: by inducing and maintaining chronic low-grade inflammation, by producing neurotransmitters or neurotoxic molecules, by directly stimulating the enteric nervous system and signalling to the brain via the vagus nerve, by producing hormones that affect not only the endocrine system but also the nervous system. This gives the gut bacteria the ability to influence stress, sleep, memory, and mood, for example. And these are all affected by CFS and IBS.

Furthermore, these symptoms are also common in fibromyalgia, which shares many symptoms with CFS, including chronic generalised pain, fatigue, sleep disturbances, headaches, cognitive dysfunction, and those gastrointestinal symptoms described above. Fibromyalgia is actually very common among CFS patients - it is estimated that between 35 to 70% of patients with CFS also have fibromyalgia. Some researchers even argue that they are the same disease with a different predominance of symptoms – pain in fibromyalgia, fatigue in CFS. Furthermore, fibromyalgia is usually also associated with IBS. Is it possible that these are all connected, maybe even having the same cause?  

It does not sound that unlikely, but it will have to be answered by science.


Can You Test for CFS?

CFS is hard to diagnose since its cause is unknown. CFS is therefore diagnosed by ruling out other conditions that may cause similar symptoms, such as thyroid gland problems, lupus, rheumatoid arthritis, HIV infection, Lyme disease, tuberculosis, or hepatitis. This is usually done through a test battery to exclude other diseases, including blood and urine tests.

Read more from Sara Adaes


Aaron LA, et al (2000). Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med, 160(2):221-7. doi: 10.1001/archinte.160.2.221

Collatz A, Johnston SC, Staines DR, Marshall-Gradisnik SM (2016). A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Clin Ther, 38(6):1263-1271.e9. doi: 10.1016/j.clinthera.2016.04.038

Galland L (2014). The gut microbiome and the brain. J Med Food, 17(12):1261-72. doi: 10.1089/jmf.2014.7000

Giloteaux L, et al (2016). Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 4(1):30. doi: 10.1186/s40168-016-0171-4

Kennedy PJ, et al (2014). Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol, 20(39):14105-25. doi: 10.3748/wjg.v20.i39.14105

Lakhan SE, Kirchgessner A (2010). Gut inflammation in chronic fatigue syndrome. Nutr Metab (Lond), 7:79. doi: 10.1186/1743-7075-7-79

Maes M, et al (2012). Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. J Affect Disord, 136(3):933-9. doi: 10.1016/j.jad.2011.09.004

Rimbaut S, et al (2016). Chronic fatigue syndrome - an update. Acta Clin Belg, 17:1-8. [Epub ahead of print] doi: 10.1080/17843286.2016.1196862

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