What is already known
Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a disease characterized by prolonged, extreme exhaustion that doesn’t improve with rest, mental clouding, muscle pain and gut problems — among other symptoms. The triggers of ME/CFS are unknown, and although patients have altered gut microbiotas, the consequences of microbial changes associated with ME/CFS remain unclear.
What this research adds
Two independent teams of researchers found that ME/CFS is associated with reduced levels of gut microbes able to produce the fatty acid butyrate—a metabolite that is involved in preserving the integrity of the gut barrier and modulating the immune system. One study showed that people with short-term ME/CFS had reduced microbiota diversity, including a decrease in butyrate-producing microbes, whereas those with long-term disease had reduced blood levels of immunomodulatory metabolites. The second study also found reduced levels of butyrate metabolites in stools from people with ME/CFS.
Conclusions
The findings may help to develop new diagnostic tools and better animal models of ME/CFS.
Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a debilitating disease that affects up to 2.5 million people in the United States alone. Now, two independent teams of researchers found that ME/CFS is associated with reduced levels of gut microbes able to produce the fatty acid butyrate — a metabolite that is involved in preserving the integrity of the gut barrier and modulating the immune system.
The results of the studies, both published in Cell Host & Microbe, may help to develop new diagnostic tools and better animal models of ME/CFS.
“This research demonstrates that there are robust bacterial signatures of gut dysbiosis in individuals with ME/CFS,” says Brent Williams at Columbia University, who is a senior author on one of the studies. “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 characterized by prolonged, extreme exhaustion that doesn’t improve with rest, mental clouding, muscle pain and gut problems — among other symptoms. The triggers of the condition are unknown, and although patients have altered gut microbiotas, the consequences of microbial changes associated with ME/CFS remain unclear.
To investigate the link between ME/CFS and the gut microbiota, the team led by Williams analyzed stool samples from 106 people with ME/CFS and 91 healthy people. Another group of scientists led by Julia Oh at the Jackson Laboratory looked at stool and blood samples from 149 people with ME/CFS and 79 healthy controls.
Reduced butyrate
Williams’s study found that the levels of Faecalibacterium prausnitzii and Eubacterium rectale, two butyrate-producing microbes that are common in the human gut, were reduced in people with ME/CFS.
Lower levels of F. prausnitzii were associated with more severe fatigue, the team found. The results may provide targets for diagnostic tools and therapeutic approaches, the researchers say.
“While these findings don’t unequivocally demonstrate causative relationships between disturbances in the microbiome and symptoms, these microbiome-symptom relationships present potentially actionable, manipulatable targets for future therapeutic trials,” Williams says. “These trials could perhaps focus on dietary, probiotic, prebiotic, or synbiotic interventions and could provide direct evidence that gut bacteria influence chronic symptom presentation.”
Altered metabolites
Oh’s study showed that people who had ME/CFS for less than four years had reduced levels of butyrate producers, including Roseburia and F. prausnitzii. Indeed, gut and plasma butyrate levels were reduced in those people.
The gut microbiotas of people who had ME/CFS for more than 10 years had reverted to a composition similar to those of healthy controls, the researchers found. However, people with long-term disease had reduced blood levels of immunomodulatory metabolites.
Because ME/CFS shares many symptoms with ‘long COVID’, unraveling the biological mechanisms of the condition may be relevant also for the COVID-19 pandemic, the researchers say.
“It’s important to note that this research shows correlation, not causation, between these microbiome changes and ME/CFS,” Oh says. “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.”
