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Hidden Link: The Microbiome and CFS

Evidence-based Reviewed Article

An image of microbiomeThe term “microbiome” refers to microorganisms (microbiota) and their genomes that exist in and on the human body. This includes millions of bacteria, fungi, viruses, parasites, and protozoa. Each human has roughly 600,000 genes from microbes, compared to only 23,000 from human sources. The gut microbiome has diverse microbial inter-species interactions that can be either beneficial or harmful. One example of an interaction between this is the microbiome and CFS (Chronic Fatigue Syndrome).

What Is Chronic Fatigue Syndrome?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness affecting up to 24 million people globally, for which there is currently no specific therapies. Chronic fatigue syndrome (CFS), or myalgic encephalomyelitis, is a long-term condition characterized by unexplained debilitating fatigue or exhaustion, brain fog or cognitive dysfunction, and gastrointestinal disturbances.

Other symptoms of CFS include:

  • Sleep disruption
  • Chest pain
  • Flu-like symptoms
  • Thinking and/or memory problems
  • Hair loss
  • Irregularities in body temperature dizziness
  • Muscle aches, cramps, or spasms
  • Rash
  • Weight fluctuations
  • Sore throat

Chronic Fatigue Syndrome (CFS) and Adrenal Fatigue Syndrome (AFS) are interconnected through the NeuroEndoMetabolic (NEM) Stress Response system, a comprehensive framework that describes how different systems of the body interact in response to stress. The NEM stress response encompasses six circuits—neuroaffective, metabolic, hormonal, cardionomic, inflammation, and detoxification—each involving various organs and pathways. Both CFS and AFS can be viewed as manifestations of an overwhelmed or dysregulated NEM stress response.

In the case of AFS, the hormonal circuit, which includes the adrenal glands, becomes imbalanced. Stress hormones like cortisol may be produced in suboptimal levels, affecting the body's ability to handle stress and contributing to persistent fatigue. Similarly, CFS, although not fully understood, may be related to abnormalities in the neuroaffective and metabolic circuits of the NEM stress response system. Both conditions might involve multiple circuits, including the inflammation and detoxification circuits, thereby explaining their wide range of symptoms, including unrefreshing sleep, cognitive difficulties, and exercise intolerance.

The exact cause of  Chronic Fatigue Syndrome remains a mystery, although it has been associated with viral infections. However, research indicates that in individuals with ME/CFS, there can be significant rewiring of the bacterial networks in the microbiome.

Microbiome and CFS Linked

Fatigue and Butyrate

New studies suggest that there is a link between the human microbiome and CFS. Based on the findings of a recent study, there might be a link between the degree of health-promoting gut bacteria and the severity of fatigue symptoms. A study published in the journal Cell Host & Microbe suggests that the health-promoting gut bacterium Faecalibacterium prausnitzii may significantly reduce exhaustion in persons who experience CFS (Guo).

Researchers measured the level of a specific bacteria in fecal samples taken from 106 CFS patients. The results were compared to 91 healthy subjects to see how gut microbiomes differ between the two. Subsequently, findings revealed that levels of the gut bacteria F. prausnitzii and Eubacterium rectale were decreased in CFS subjects. These two can be categorized as “good” bacteria. Furthermore, they play a critical role in the production of butyrate.

Lack of Butyrate

Butyrate, which is a gut microbial metabolite, plays a key role in the health of the gut microbiome and is linked to mucosal immune regulation. Specifically, it’s a fatty acid in the gastrointestinal microbiome that helps to break down fiber. Microbiome diversity can be altered in CFS patients, and microbes that produce butyrate can be reduced.

Reduced butyrate levels in persons with CFS could lead to inflammation in the gut and a weakened gut barrier. This combination could trigger an inflammatory response that extends from the gut to the brain. Additionally, decreased level of butyrate is linked to several diseases, including colon cancer, inflammatory bowel disease (IBS), and insulin resistance.

Furthermore, lower levels of the bacteria F. prausnitzii are also associated with the severity of fatigue CFS symptoms. Still, it is unknown whether a decrease in F. prausnitzii is a cause or consequence of CFS.

Microbiome and Abnormalities in CFS

A different 2023 study in Cell Host & Microbe analyzed gut microbiome-host interactions in short- and long-term chronic fatigue syndrome patients (Xiong). Findings revealed that:

An image of the microbiome

  • CFS patients experience reduced gut microbial diversity and increased plasma sphingomyelins (linked to cognitive impairment).
  • With decreased butyrate, short-term patients showed significant gut microbial dysbiosis.
  • Long-term patients showed largely resolved microbial dysbiosis. However, they had more significant metabolic and clinical phenotypic immune-related alterations.

As such, these findings indicate that the immune system becomes disrupted in patients with CFS. Furthermore, they point to the possibility that microbiome abnormalities may lead to an abnormal immune response over time.

Possible Causes of Low Butyrate in CFS

This study suggested that the mechanism of the problem may be because:

  • Individuals with CFS are usually deficient in one of the two genes (the “but” gene) necessary for the production of butyrate using the acetyl-CoA pathway gene. Also, a functional analysis further suggested that the bacteria using that gene were missing in individuals with CFS.
  • There were reduced levels of the substance acetate. Butyrate-producing bacteria require acetate to produce butyrate.
  • One of the four butyrate-producing pathways – the CoA pathway (dominant) – was responsible for the butyrate deficiency (Xiong).

Other Potential Reasons for Butyrate Deficiency

The exact cause of low butyrate-producing bacteria in CFS is unclear. However, low levels of physical activity could play a role in this problem. Recent studies suggest that physical exercise stimulates butyrate-producing bacteria that are low in CFS. One study found an association between reduced butyrate levels and fatigue, which suggests that the lower activity levels of more fatigued individuals with CFS may contribute to lower butyrate levels.

Still, there are several possibilities including, reduced gut motility, blood flows to the gut, as well as reduced circulation of bile acids. Furthermore, low butyrate levels are found in a variety of conditions, such as inflammatory bowel disease (IBD), IBS, celiac disease, colorectal cancer, and obesity. As such, it may be safe to say that low activity levels are not responsible alone for all the gut issues in individuals with CFS.

Microbiome and CFS Connected to IBS

The connection between the microbiome and CFS appears to be multifaceted, and when irritable bowel syndrome (IBS) is thrown into the mix, it becomes even more complex.

IBS is a common, but not a universal comorbid condition present in persons with CFS. It’s characterized by symptoms such as abdominal pain, bloating, or cramping typically associated with a bowel movement or changes in the appearance of stool (e.g. hard-packed or diarrhea), and frequency of bowel movement.

When looking and the microbiome and CFS, studies indicate that having IBS with CFS can make a significant difference in the diversity of your gut microbiome. Specifically, whether CFS patients had or didn’t have IBS showed in the alpha diversity of the gut bacteria. In this case, alpha diversity refers to the diversity of the complex ecosystems of the gut. In fact, the higher the species alpha diversity of the bacteria in your gut, the greater its health, resiliency, and productivity should be. However, research findings suggest that some CFS patients’ gut ecosystems are not as diverse and resilient as others.

The Gut Microbiome and the Immune Response

An image of the body's immune responseThe body’s microbiome plays a significant role in your overall health. Early research findings suggest that a person’s microbiota has a direct effect on several diseases, such as asthma, celiac disease, cancer, diabetes, inflammatory bowel disease, and heart disease. A dysfunction between the microbiome and the host is connected to these diseases.

As such, there seem to be potential mechanisms whereby your microbiome can impact your immune system. The highest levels of microbes and lymphoid tissue that support immune responses are found in your GI tract. Here, the immune system and the microbiota have a harmonious relationship.

According to an article published in the Journal of Clinical & Cellular Immunology, your body’s immune system benefits from the microbiome because it helps the body resist the colonization of pathogens. However, it’s also possible for the microbiome to alter the body’s response to a particular pathogen and limit the efficiency of prescription drugs and how well your immune system functions.

As such, the relationship between the immune system, the microbiome and CFS is a complex one and requires more research before much can be said about what may cause observed changes.

Is Chronic Fatigue Syndrome in Your Head?

One thing can be said for certain though: that CFS is not just in your head. Research findings point to biological markers for CFS in gut bacteria and inflammatory microbial agents in the blood. A study published in the journal Microbiome describes researchers correctly identifying CFS in 83 percent of patients through stool samples and blood work. This gave the researchers the opportunity to provide a noninvasive examination and some level of understanding regarding the cause of CFS.

Researchers made two significant findings:

  • Via DNA sequencing, they found the stool samples in CFS patients had less diversity in bacteria present in the gut and even fewer were anti-inflammatory.
  • The blood samples showed markers of inflammation that they hypothesized may have resulted from a "leaky" gut stemming from intestinal issues. This allows bacteria to enter the blood.

Thus, CFS is not merely in your imagination. It is characteristic of significant gastrointestinal and inflammatory changes. Signs of a biological abnormality provide evidence against the notion that the disease is only psychological in nature. There are significant physiological differences between individuals with CFS and those who do not suffer from the condition.

Microbiome and CFS: Remedying CFS

To date, there is no specific therapies or known ways to remove CFS. However, different remedies and lifestyle changes have been used to ameliorate and manage CFS symptoms.

Some options that are usually recommended include:

  • Developing healthy sleep habits
  • Practicing relaxation techniques, such as deep breathing, massage, and meditation
  • Lower anxiety
  • Gentle exercises, such as yoga
  • Water therapy
  • Maintaining a balanced and healthy diet
  • Taking nutritional supplements

CFS Therapies Related to the Microbiome

A different set of therapies for CFS may be implicated by the relationship between the microbiome and CFS. One bacterium in particular, Faecalibacterium prausnitzii, is implicated in the health of the microbiome and CFS. Supporting these bacteria may thus help symptoms.

An adequate intake of pectins seem to stimulate the growth of various beneficial bacteria, including Bifidobacterium, Lactobacillus species, Faecalibacterium prausnitzii, and Eubacterium rectale. Pectins are complex, plant-derived carbohydrates that cannot be digested by human enzymes. However, they can be easily broken down by certain commensal bacteria in your gut.

Inulin is another prebiotic that can be used to increase the level of F. prausnitzii in the intestinal microbiota.

The Best Probiotics for Chronic Fatigue Syndrome

An image of probiotics and the gutProbiotics are “friendly” microorganisms, usually bacteria or yeasts, that reside in the gastrointestinal tract or on other mucosal surfaces. They exert beneficial effects on your health. Some significant probiotic benefits for your microbiome and CFS include:

  • Increase the number of healthy bacteria in the gut, and reduce unhealthy bacteria.
  • Boost the protective ability of the gut wall to serve as a barrier to prevent unwanted compounds from entering.
  • Reduce your body’s production of inflammation-producing compounds, minimizing inflammation in your gut.

Microbiome and CFS: The Best Probiotic Strains for CFS

There are many different strains that can be beneficial in reducing inflammation, supporting the immune system, and preventing the growth of bad bacteria. These include:

  • Bifidobacterium bifidum – supports the immune system and inhibits harmful bacteria. One study published in Gut Microbes found that 6-8 weeks of Bifidobacterium infantis supplementation reduced C-reactive protein, TNF-alpha, and IL-6 levels in chronic fatigue syndrome patients.
  • Bifidobacterium longum – reduces inflammation, and removes lead and heavy metals. A study suggests that Bifidobacterium longum inhibits inflammation by regulating the balance of the immune system, improving intestinal barrier function, and helping prevent the growth of harmful pathogens.
  • Akkermansia muciniphila – beneficial traits include facilitating the growth of butyrate producers via producing acetate, which minimizes a loss of colonic bilayer. In so doing, reduces inflammation.
  • Lactobacillus acidophilus - can help reduce fatigue after exertion.

However, it is essential that you talk to your healthcare provider before taking any of these supplements. Discuss with your healthcare provider the possible benefits and harms of any remedy, such as medicines and other therapies.

Supplementation

These Dr Lam supplements may help support gut health and your microbiome through CFS. However, don't take any new supplements without talking to a doctor first.

Digestive Enzymes

Adrezyme

Adrezyme is a proprietary formulation that’s packed with a variety of enzymes. These enzymes help with the breakdown of fat, carbohydrates, proteins, dairy, grains, and indigestible fibers.

Glutelyze

Glutelyze is a digestive enzyme formula that supports the digestive process, by digesting gluten and carbohydrates. It breaks down difficult-to-digest proline-containing peptides, found in dairy products and cereal grains.

Stomazyme

Stomazyme is a proprietary blend containing a combination of enzymes, as well as betaine hydrochloride and ox bile extract. It helps to support healthy digestion and has the potential to aid with the production of stomach acid, greater bile production, and the breakdown of carbs, fat, and proteins.

Probiotics

Pro-B

Pro-B is a potent probiotic formula that contains Lactobacillus acidophilus, which helps with digestion and supports healthy skin and the health of your immune system. Also, it’s beneficial in maintaining the "good bacteria" in your gut that support proper digestion and absorption of nutrients from food. Additionally, it can help you to maintain healthy intestinal flora and help support a balanced mycobiome.

Pro-Y

Pro-Y contains Saccharomyces boulardii, which is a strain of yeast with probiotics benefits. It may support a healthy gut flora balance, as well as the health and balance of the intestinal tract against environmental and internal stressors.

The Takeaway

The human microbiome and CFS are connected, in that changes in the microbiome are correlated to the condition. As such, it’s essential that the microbiome's health be maintained and the growth of good bacteria is supported. If you think you may have CFS and are unsure about your symptoms, Dr. Lam's Adrenal Fatigue Recovery Program can help you! In this program, you'll learn how to use supplements, which foods to eat, which exercises are best for you, and about your stage of adrenal fatigue. This course focuses on helping you make informed choices and avoid the pitfalls Dr. Lam faced in his recovery journey.

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References

Cornell University. (2016, June 27). Chronic fatigue syndrome is in your gut, not your head. ScienceDaily. Retrieved June 2, 2023 from www.sciencedaily.com/releases/2016/06/160627160939.htm

Groeger, D., O'Mahony, L., Murphy, E. F., Bourke, J. F., Dinan, T. G., Kiely, B., Shanahan, F., & Quigley, E. M. (2013). Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut microbes, 4(4), 325–339. https://doi.org/10.4161/gmic.25487

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

Guo, C., Che, X., Briese, T., Ranjan, A., Allicock, O., Yates, R. A., Cheng, A., March, D., Hornig, M., Komaroff, A. L., Levine, S., Bateman, L., Vernon, S. D., Klimas, N. G., Montoya, J. G., Peterson, D. L., Lipkin, W. I., & Williams, B. L. (2023). Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS. Cell Host & Microbe, 31(2), 288-304.e8. https://doi.org/10.1016/j.chom.2023.01.004

Rivera-Amill V. (2014). The Human Microbiome and the Immune System: An Ever Evolving Understanding. Journal of clinical & cellular immunology, 5(6), e114. https://doi.org/10.4172/2155-9899.1000e114

Roman, P., Carrillo-Trabalón, F., Sánchez-Labraca, N., Cañadas, F., Estévez, A. F., & Cardona, D. (2018). Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review. Beneficial microbes, 9(4), 603–611. https://doi.org/10.3920/BM2017.0125

Xiong, R., Gunter, C., Fleming, E., Vernon, S. D., Bateman, L., Unutmaz, D., & Oh, J. (2023). Multi-'omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients. Cell host & microbe, 31(2), 273–287.e5. https://doi.org/10.1016/j.chom.2023.01.001

Yao, S., Zhao, Z., Wang, W., & Liu, X. (2020). Bifidobacterium Longum: Protection against Inflammatory Bowel Disease. Journal of Immunology Research, 2021. https://doi.org/10.1155/2021/8030297

Dr. Lam’s Key Question

The connection between the microbiome and CFS is not fully understood. However, research suggests that an altered microbiome with low levels of butyrate triggers inflammation. Furthermore, levels of the gut bacteria F. prausnitzii and Eubacterium rectale seem to decrease in CFS subjects.

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