Long-term fatigue and poor condition may be due to lack of butyrate

Author: Zhao Bei

Have you ever been extremely tired in your life, and even rest and sleep can't eliminate the fatigue? It's not that you are too lazy or too depressed, it may be that you are really sick.

There is a disease called chronic fatigue syndrome (CFS) in medicine, in which patients experience extreme fatigue for at least 6 months without underlying medical diseases. This fatigue worsens with physical or mental activity, but does not improve after rest, and is accompanied by symptoms such as depression, headache, gastrointestinal disorders, and allergies. This disease is also called myalgic encephalomyelitis (ME), sometimes abbreviated as ME/CFS, and there is also a new term called systemic exertion intolerance disorder (SEID).

Chronic fatigue syndrome not only affects mood, social interaction, and work efficiency, but is also prone to stroke, autoimmune diseases, etc. Unfortunately, there is no particularly effective treatment for chronic fatigue syndrome, and there is not even any symptomatic medicine. The only way to alleviate the symptoms is through conversation, diet therapy, acupuncture, massage, exercise, and other auxiliary means.

In order to develop treatments for chronic fatigue syndrome, the cause must be found. The causes of chronic fatigue syndrome are very complex. Viral infections, immune system disorders, hormonal imbalances, malnutrition, stress trauma, etc. may all be the culprits of chronic fatigue syndrome. Scientists collected and analyzed blood, feces and other samples from patients, looking for the differences between chronic fatigue syndrome patients and healthy people in the complex data, and what is the key to the disease. They found:

● Chronic fatigue syndrome patients have abnormal states of multiple immune cells[1]. For example, the number of pro-inflammatory cells is higher, which puts the body in a state of chronic inflammation. The number of natural killer cells that are responsible for cleaning up "garbage" in the body decreases, causing necrotic cells to accumulate in the body.

● The metabolism of patients with chronic fatigue syndrome is also abnormal[1]. Each of our cells is like a small factory, processing hundreds of "products". Key nutrients such as amino acids, lipids, sugars, adenosine, etc. are constantly assembled, decomposed and processed in cells every minute and every second. The transformation is like a complex production line. From raw materials to products, each step is important. This complex process is metabolism. During the metabolic process, different cells show their own specific functions, such as replication, movement, and signal exchange. Scientists have found that 80% of the "production lines" of patients with chronic fatigue syndrome have lower production capacity than healthy people, production is not active, cell energy and metabolites are insufficient, and function is definitely impaired.

● The intestinal flora of patients with chronic fatigue syndrome is disordered, and the intestinal epithelial cells of these patients are often more fragile, making them prone to intestinal problems such as enteritis.

A recent article published in the journal Cell Host & Microbe found that patients with chronic fatigue syndrome lack key intestinal bacteria that synthesize butyrate: Faecalibacterium prausnitzii and Eubacterium rectale[2]. Moreover, the lack of these intestinal bacteria occurs in the early stages of chronic fatigue syndrome patients, which may serve as an early detection indicator of the disease.

It can be seen that the state of immune cells, human metabolism, and intestinal flora disorders all have an impact on chronic fatigue syndrome. But why do intestinal bacteria, which seem to have nothing to do with fatigue, also get involved? Why is butyrate in the intestine related to fatigue?

Butyrate is a type of short-chain fatty acid and is currently a widely recognized metabolite that is beneficial to health.

(1) Butyrate can promote the regeneration of intestinal epithelial cells, ensuring the integrity of the intestinal epithelium and protecting it from the invasion of toxins and pathogens.

(2) In addition, butyrate can also reduce inflammation in the intestines and excite macrophages, which are the “patrol police” in the intestines. Excited macrophages can more effectively resist the invasion of bacteria and viruses [3].

(3) Butyrate is also an important source of energy for cells. 70% of the energy for intestinal cells comes from butyrate[4].

Although butyrate is important, it cannot be synthesized by our human body. Butyrate is a fermentation product of carbohydrates such as cellulose and starch. These carbohydrates are not only difficult to digest, but we do not have the enzymes to decompose them, so we can only rely on intestinal flora to decompose and ferment them. Moreover, not all intestinal flora have the ability to ferment cellulose. Only a few bacteria such as Faecalibacterium prausnitzii, Ruminococcus bromorum, and Eubacterium rectum can do it.

Butyrate has a wide range of effects in our body. Although butyrate is produced by intestinal flora in the intestinal cavity, it can easily pass through the intestinal epithelial cells, enter the blood circulation and travel throughout the body. Moreover, most cells recognize butyrate, and there are butyrate receptors on the cell surface that can bind to butyrate and thus be affected by butyrate. Therefore, many diseases such as diabetes, obesity, and neurological diseases are related to the butyrate content in our body.

Knowing the functions and processing methods of butyrate, it is not difficult to see how important the intestinal flora that synthesizes butyrate is to our health. So will supplementing this type of bacteria or supplementing butyrate help alleviate the symptoms of chronic fatigue syndrome?

Currently, with the cooperation of scientists and clinicians, some clinical trials of changing diet or supplementing prebiotics have been launched, including supplementing patients with chronic fatigue syndrome with fiber-rich foods, fermented foods, coenzyme Q10, and chocolate rich in cocoa polyphenols [5]. Dietary changes have indeed shown the effect of improving symptoms and are expected to be promoted among patients as an auxiliary treatment method.

In addition, clinical data on the supplementation of patients with probiotics or fecal microbiota therapy are also very encouraging. Probiotics or fecal microbiota transplantation can restore the homeostasis of the intestinal flora and lead to significant long-term improvements in energy and physical fitness in more than half of the patients [6-8].

Of course, probiotics for the treatment of chronic fatigue syndrome still need more data from large-scale clinical trials, and need to be continuously optimized before they can be transformed into drugs. But after reading this article, I believe everyone has realized the importance of butyrate. We can usually eat more fiber-rich foods, such as whole grains, vegetables, fruits, nuts and beans. This is the most effective way to increase butyrate and other short-chain fatty acids, and it is also beneficial to improve the composition of intestinal flora, helping us to live energetically and healthily!

References:

1. Tomas C, Newton J. Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review. Biochem Soc Trans. 2018;46(3):547-553.
2. Guo C, Che X, Briese T, et al. Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS. Cell Host Microbe. 2023;31(2):288-304.e8.
3. J. Schulthess, S. Pandey, M. Capitani, et al., The short fatty chain acid butyrate imprints an antimicrobial program in macrophages. Immunity, 50 (2019), pp. 432-445.e7, 10.1016/j.immuni.2018.12.018
4. JG LeBlanc, F. Chain, R. Martín, et al., Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb. Cell Fact., 16 (2017), p. 79.
5. Campagnolo, N., Johnston, S., Collatz, A., et al., Dietary and Nutrition Interventions for the Therapeutic Treatment of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review. J. Hum. Nutr. Diet. 2017, 30, 247–259.
6. Sullivan, Å., Nord, CE & Evengård, B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J 8, 4 (2009).
7. Borody, TJ, Nowak, A., Finlayson, S. The GI Microbiome and Its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy The GI Microbiome and Its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy. ACNEM J. 2012, 31, 3–8.
8. Borody, T. Bacteriotherapy for Chronic Fatigue Syndrome: A Long-Term Follow up Study. In Proceedings of the 1995 CFS National Consensus Conference; 1995.

This article is a work supported by Science Popularization China Starry Sky Project

Author: Zhao Bei

Reviewer: Wang Qiang, deputy chief physician, Department of Gastroenterology, Peking Union Medical College Hospital

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.