Chronic fatigue linked to alterations in the gut microbiome

The myalgic encephalomyelitis (MS) o chronic fatigue syndrome (CFS) It is a disease that causes intense fatigue that is not related to the patient’s activity, nor does it improve when resting, and for which there is currently no cure. Its origin is unclear, but it has been linked to some risk factors such as viral infections (as with persistent COVID, most cases are attributed to exposure to viruses and other pathogens) and hormonal or immunological disorders, among others. .

Therefore, people who suffer from it do not only face obstacles immediate at the level of symptoms (severe fatigue, post-exertion discomfort, pain, sleep interruption and gastrointestinal problems) but obtaining a diagnosis and medical support can be an ordeal on many occasions, since there are no definitive results of laboratory tests or other biomarkers that strongly confirm CFS.

Two new studies have investigated the relationship of chronic fatigue syndrome with the

microbiomay the metabolites produced by microbes, and have found an association between the disease and a lower presence in the microbioma gastrointestinal of microbes that are responsible for producing the butyrate fatty acidwhich plays an important role in protecting the integrity of the intestinal barrier and in modulating the immune system.

The results showed significant associations between the severity of chronic fatigue symptoms and the levels of certain butyrate-producing gut bacteria.

The results of these studies indicate that these changes in the microbiome could partly explain the impaired immune system in patients with chronic fatigue syndrome. “It is important to note that this research shows correlation, not causation, between these changes in the microbiome and ME/CFS,” said Julia Oh, an associate professor in the Jackson Laboratory and lead author of one of the two papers, published in Cell Host & Microbe–. But these findings are a prelude to many other mechanistic experiments that we hope to do to better understand the disease and its underlying causes.”

Brent L. Williams, associate professor at Columbia University and lead author of the other paper, also published in Cell Host & Microbestates that they have shown that “there are robust bacterial signatures of disbiosis intestinal in individuals with ME/CFS” and that their findings have revealed “structural and functional alterations of the microbiome in a chronic disease that affects the quality of life of millions of people”.

Gut bacteria influencing chronic fatigue symptoms

The symptoms of chronic fatigue syndrome differ among those affected, and those affected can have very different medical histories, making it more difficult to study its causes and find treatments. For this reason, the two groups of researchers have highlighted the importance of carrying out studies such as theirs in which they have analyzed data from a large number of patients.

Julia Oh and her colleagues compared microbiome samples from 74 people who had been diagnosed with CFS in the previous four years with that of 75 patients who had experienced symptoms of the disease for more than 10 years, and with that of 79 healthy individuals, matched by age and sex. In addition, they analyzed plasma samples from the participants. What they found were microbial and metabolic traits that differed between the groups, including multiple biomarkers that were specific to people with CFS.

As we said, they discovered that the microbiomes of patients with the disease in the short term presented changes with respect to their diversity, and that the most relevant was a reduction in the number of butyrate-producing microbes. However, the gut microbiome of those with long-term disease had been restored and was more similar to that of healthy controls, but these patients had changes in the metabolites of your blood plasmaincluding many of those related to the immune system.

Biomarkers for chronic fatigue syndrome

Looking further, the Jackson laboratory team found that low-abundance microbes involved in the production of tryptophan, butyrate and propionic acid were largely absent in people with CFS. These substances are important in regulating metabolic and endocrine functions, including the modulation of inflammatory responses. Given the critical roles that butyrate plays in intestinal cells as a major source of energy and an anti-inflammatory, the researchers focused more on the butyrate pathway to better understand the role it might play in CFS.

They found that plasma isobutyrate is depleted in people with chronic fatigue syndrome, and that microbiome data also predicts decreased butyrate abundance and changes in the ability of the gut microbiome to metabolize or synthesize short-chain fatty acids. In general, the pathway affects dozens of plasmatic metabolites, and its alteration can have both metabolic and immunological consequences. These features point to ways to increase the accuracy of classification and the development of new therapeutic strategies.

Bacterial signatures of gut dysbiosis in people with CFS

For its part, the Williams study examined the microbiomes of 106 people with ME/CFS and 91 healthy individuals matched by age, sex, place of residence and socioeconomic level, and also analyzed metabolites in feces, finding reduced levels of butyrate metabolites in patients with ME/CFS. The results showed significant associations between the severity of chronic fatigue symptoms and the levels of specific species of gut bacteria, particularly bacteria Faecalibacterium prausnitziibutyrate producer.

The researchers have explained that while their findings cannot prove a causal relationship between microbiome alterations and symptoms and further research is needed before the results can be applied to new treatments, they believe they will be very useful in developing new diagnostic techniques and trials that focus on “dietary, probiotic, prebiotic or symbiotic interventions”, and that “could provide direct evidence that gut bacteria influence the presentation of chronic symptoms”.

Implication of the study of the intestinal microbiota in patients with CFS

Speaking to SMC Spain Jordi Casademontdirector of the Internal Medicine Service and head of the Fibromyalgia and Chronic Fatigue Syndrome Functional Unit at the Sant Pau Hospital in Barcelona, ​​points out that “intestinal microbiota studies are very complex to analyze, and for practical purposes there is almost nothing that can be used in the clinic, it is not possible to go, for the moment, beyond describing the finding”.

“The intestinal microbiota is, without a doubt, a very interesting field of study, but for now we could say that it is in the phase of collecting information and not drawing too many conclusions. There are enormous variations between individuals related to many parameters that we barely know and it is risky to try to draw conclusions that are of practical use. The same authors of these two articles insist that the data does not imply causation, simply a relationship”.

In statements to the same medium, Joaquim Fernández SolàProfessor of Medicine at the University of Barcelona and coordinator of the Central Awareness Unit at the Hospital Clínic de Barcelona explained: “These articles provide biomarkers which may be useful in assessing gastrointestinal involvement in ME/CFS patients. However, as the same authors already state in the limitations of the studies, these are not diagnostic markers of disease, but rather the process of gastrointestinal dysfunction. Nor do they immediately imply that they can act directly on the microbiota and improve CFS/ME symptoms. We are still at the beginning of scientific knowledge of the microbiota and its mediating role in multiple diseases, including ME/CFS”.


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