Microbiome Changes May Be a Signature for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Researchers have found differences in the gut microbiomes of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) compared to healthy controls. 

ME/CFS is a serious, chronic, and debilitating disease characterized by a range of symptoms, including fatigue, post-exertional malaise, sleep disturbance, cognitive difficulties, pain, and gastrointestinal issues. The causes of the disease are unknown and there are no treatments.

In one study, senior author Brent L. Williams, Ph.D., and their collaborators analyzed the genetic makeup of gut bacteria in fecal samples collected from a geographically diverse cohort of 106 people with ME/CFS and 91 healthy controls. The results revealed key differences in microbiome diversity, quantity, metabolic pathways, and interactions between species of gut bacteria.

Dr. Williams and his colleagues found that people with ME/CFS had abnormally low levels of several bacterial species compared to healthy controls, including Faecalibacterium prausnitzii and Eubacterium rectale. These health-promoting bacteria produce a short chain fatty acid called butyrate. 

More detailed metabolomic analyses confirmed that a reduction in these bacteria was associated with reduced butyrate production in ME/CFS. Butyrate is the primary energy source for cells that line the gut, providing up to 70% of their energy requirements, support for the gut immune system, and protection against diseases of the digestive tract. 

The findings indicate that imbalances in these 12 species of bacteria could be used as biomarkers for ME/CFS classification, potentially providing consistent, measurable targets to improve diagnosis.

In another study at the Jackson Laboratory in Farmington, Connecticut, Julia Oh, Ph.D., teamed up with other ME/CFS experts to study microbiome abnormalities in different phases of ME/CFS. Dr. Oh’s team collected and analyzed clinical data, fecal samples, and blood samples from 149 people with ME/CFS who had been diagnosed within the previous four years (74 short-term) or who had been diagnosed more than 10 years ago (75 long-term) and 79 healthy controls.

The results showed that the short-term group had less microbial diversity, while the long-term group established a stable, but individualized gut microbiome similar to healthy controls. Dr. Oh and her colleagues found lower levels of several butyrate-producing species, including F. prausnitzii, especially in the short-term participants. There was also a reduction in species associated with tryptophan metabolism in all ME/CFS participants compared to controls.

Both studies identify potential biomarkers for ME/CFS, which may inform diagnostic tests and disease classification. Understanding the connection between disturbances in the gut microbiome and ME/CFS may also guide the development of new therapeutics.


Cheng Guo, Xiaoyu Che, Thomas Briese, Amit Ranjan, Orchid Allicock, Rachel A. Yates, Aaron Cheng, Dana March, Mady Hornig, Anthony L. Komaroff, Susan Levine, Lucinda Bateman, Suzanne D. Vernon, Nancy G. Klimas, Jose G. Montoya, Daniel L. Peterson, W. Ian Lipkin, Brent L. Williams. 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 DOI: 10.1016/j.chom.2023.01.004

Ruoyun Xiong, Courtney Gunter, Elizabeth Fleming, Suzanne D. Vernon, Lucinda Bateman, Derya Unutmaz, Julia Oh. Multi-‘omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients. Cell Host & Microbe, 2023; 31 (2): 273 DOI: 10.1016/j.chom.2023.01.001

NIH/National Institute of Neurological Disorders and Stroke. “Studies find that microbiome changes may be a signature for ME/CFS: Altered gut microbes linked to debilitating chronic disease.” ScienceDaily. ScienceDaily, 8 February 2023. <www.sciencedaily.com/releases/2023/02/230208124337.htm>.

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