Scientists Find Links to Chronic Fatigue Syndrome in Genes and in the Gut Microbiome
Two studies present new data on ME/CFS, offering “credibility and validity” to the experiences of patients struggling with symptoms
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In the 1980s, outbreaks of a strange illness resembling mononucleosis swept through New York and Nevada. Patients reported debilitating fatigue and pain, among other symptoms. Experts were “baffled and skeptical,” Philip M. Boffey wrote in the New York Times in 1987.
“Whatever it is, it seems to be growing in frequency,” Anthony L. Komaroff, then the director of general medicine at Brigham and Women’s Hospital in Boston, told the newspaper at the time. “Literally every time I say to a friend that I’m studying this illness, and then describe it, they say ‘Oh, my God. My niece has it, or my next-door neighbor, or my boss.’”
With these incidents, chronic fatigue syndrome, or myalgic encephalomyelitis, broke into the national consciousness. The condition is defined by a combination of extreme exhaustion after physical or mental exertion, brain fog, dizziness and chronic pain. It often manifests after a viral or bacterial infection and affects up to 3.3 million people in the United States alone, though the vast majority have not been officially diagnosed.
Now, two new studies assert that they have found physical links to the condition, taking key steps toward long-sought avenues for diagnosis—though any diagnostic test or treatment remains far off. The first, published last month in the journal Nature Medicine, found markers in the gut microbiomes of patients experiencing symptoms. The second, a preprint that hasn’t yet been peer-reviewed and was made available last week, identified eight potential “genetic signals” linked to the illness.
“Our findings will provide credibility and validity to the experience of the people with [this condition],” Sonya Chowdhury, CEO of the U.K. charity Action for ME and a co-author of the genetic research, said at a press conference, per Science’s Catherine Offord.
Key concept: Chronic fatigue
Chronic fatigue syndrome was a term chosen by a working group from the Centers for Disease Control and Prevention, but some CFS patients argue that using the word “fatigue” does not capture the severity of symptoms.
Sufferers of what experts call ME/CFS have long fought for recognition that their condition is physically caused, rather than psychological. This effort hasn’t always been successful, and patients have struggled for decades to get doctors to treat their symptoms.
“There are things that can help alleviate symptoms, but the barrier to treatment is often the doctor’s own skepticism about the patient’s complaints,” Diana Berrent Güthe, founder of Pandemic Prep Consulting and Survivor Corps, tells Connecticut Public Radio’s Sujata Srinivasan. “Nowhere do you see more medical gaslighting than in this area. It’s like we’re playing basketball using a football and expecting the game to go on.”
In what is now the largest DNA study of ME/CFS to date, the team behind the pre-print paper analyzed the genomes of 15,579 ME/CFS patients in the U.K. as part of the DecodeME project. They compared the ME/CFS patients’ genomes to those of nearly 260,000 people without the condition, identifying eight distinct regions of the human genome that appeared different in the DNA of people with ME/CFS.
“When we dig down into these eight different genetic signals, we find genes that are related to both the immune system and the nervous system,” Chris Ponting, a geneticist at the University of Edinburgh and co-author of the DecodeME study, tells New Scientist’s Michael Marshall. “Overall, the activities of the genes in these signals are enriched in the brain’s tissues. They are more likely to be active in the brain than elsewhere, pointing to a nervous system involvement.”
The team looked for these same signals in other large sets of genetic data, but the results weren’t strongly replicated. Additionally, genetic variation can only explain a small part of a person’s risk of developing ME/CFS. For many diseases, “risk is influenced by many thousands of genetic variants, each of which on its own has only a tiny influence,” Doug Speed, a statistical geneticist at Aarhus University in Denmark who was not involved with the research, tells Science.
In the Nature Medicine study, researchers used an artificial intelligence tool to analyze four years of myriad patient data, including blood test results, gut microbiome genomics and patient-reported symptoms, from 153 ME/CFS patients at a research center in Salt Lake City, Utah. They compared these results to data from 96 healthy individuals.
Scientists found that data on the gut microbiome could predict certain symptoms in ME/CFS patients, and data on immune cells could predict symptom severity. Still, they stress that this is just one step in understanding the mysterious disease. The team hopes the work contributes to improved treatment. “We may be able to intervene—through diet, lifestyle or targeted therapies—in ways that genomic data alone can’t offer,” Julia Oh, a microbiologist at Duke University and senior author of the study, says in a statement.
Chowdhury, of the DecodeME study, tells Science that she hopes the research spurs further investigations that could lead to diagnostic tests or treatments, and her team wants to look for rare genetic variants that might be associated with ME/CFS. “We urgently need more research, more researchers coming into the field,” Chowdhury adds, and “more research funding to build on what we’ve found.”