In the last three years, as long-term COVID-19 effects have become apparent, attention has shifted to a condition called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which has many of the same characteristics and symptoms.
Two research published today in the journal Cell Host & Microbe examine ME/CFS in relation to the microbiome and the metabolites produced by microbial species.
Both investigations discovered that ME/CFS is linked to lower concentrations of bacteria known to generate the fatty acid butyrate in the gastrointestinal microbiome. These immune system disturbances in ME/CFS patients may be partially explained by these microbiome alterations.
The senior author of one of the two studies and an associate professor at the Jackson Laboratory, Julia Oh (@jjsso0), emphasizes that the study “shows correlation, not causation,” between these microbiome alterations and ME/CFS.
“But these findings are the prelude to many other mechanistic experiments that we hope to do to understand more about ME/CFS and its underlying causes.”
According to Brent L. Williams, an assistant professor at Columbia University and senior author of the second paper, this research reveals that there are substantial bacterial markers of gut dysbiosis in persons with ME/CFS.
“It helps to expand on this growing field of research by pinpointing the structural and functional disturbances in the microbiome in a chronic disease that affects the quality of life of millions of people.”
ME/CFS is a chronic, complex, systemic illness characterized by dysfunctions in the neurological, immunological, autonomic, and energy metabolism systems. It has been known for decades, but no one really knows what causes it. It is thought that, like long COVID, most cases are caused by viruses or other infectious agents. ME/CFS is challenging to investigate because it tends to be heterogeneous; not all individuals with the condition have the same medical history and symptoms. According to both study teams, this is why it’s crucial to do studies like these that examine patient data from a large number of individuals. It is critical to investigate the microbiome since it has only just come to light as a possible cause of and indicator for ME/CFS.
In Oh’s work, shotgun metagenomics was used to examine the microbiomes of 79 healthy controls and 74 patients with short-term ME/CFS (defined as those diagnosed within the preceding four years) and long-term ME/CFS (defined as those who had had symptoms for more than 10 years). The researchers also examined participant plasma samples. The patients were getting care at the Bateman Horne Center in Salt Lake City, Utah. Members of the Jackson Laboratory have worked with the center for a long time.
The study showed that the diversity of the microbiomes of people with short-term diseases had changed in a number of ways. Most significantly, they showed a decline in bacteria that are known to generate butyrate. Butyrate is known to have a significant function in immune system modulation and is crucial for maintaining the integrity of the gut barrier.
Long-term illness patients, on the other hand, had restored gut microbiomes that were more like those of healthy controls. But the metabolites in their blood plasma had changed in a number of ways, and many of those changes had to do with their immune systems. Additionally, they differed from the healthy controls in terms of the concentrations of certain immune cell types.
Williams used shotgun metagenomic sequencing to compare the microbiomes of 106 people with ME/CFS and 91 healthy people who were the same age, gender, lived in the same area, and had the same income. The Center for Solutions for ME/CFS, an interdisciplinary, multi-institutional research organization, conducted this study. They included patients from five different locations around the US, which allowed them account for any regional variations in the microbiome.
The quantity of several microbial species was also examined in this investigation. It didn’t look at plasma, but this group has already published analyses of plasma metabolomics from their cohort in other places. It did examine the metabolites in the feces, and it found that ME/CFS patients had lower amounts of butyrate metabolites.
In particular, the butyrate-producing bacterium Faecalibacterium prausnitzii was shown to be significantly correlated with levels of certain species of gut bacteria in the research by the Columbia team. Additionally, research showed that people with ME/CFS had greater levels of bacteria overall in their stools as well as problems with how different bacterial species interacted.
Before these findings can be directly used to make new treatments, more research needs to be done. However, the researchers say that these findings will help make new diagnostic tools and could help make better animal models.
Despite the fact that these results do not conclusively show a causal link between microbiome abnormalities and symptoms, Williams notes that the microbiome-symptom connections provide potentially manipulable targets for next treatment studies. These studies “could perhaps focus on dietary, probiotic, prebiotic, or synbiotic interventions and could provide direct evidence that gut bacteria influence chronic symptom presentation.”
Oh says that her future studies will help to divide patients even more by how their disease affects them, including those with conditions that are often linked to ME/CFS, such as irritable bowel syndrome and neuroinflammatory disorders. This will enable us to identify certain microbiological and metabolomic components linked to this illness, she claims.
Williams intends to use animal models for more research on his results.
“A tractable mouse model to study the gut microbiome disturbances found in ME/CFS would provide an important tool to evaluate causal hypotheses, mechanisms, and treatments,” he adds.
Source: 10.1016/j.chom.2023.01.001 & 10.1016/j.chom.2023.01.004
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