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More Clues into ME/CFS Discovered in Gut Microbiome

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Gut microbiome. Butyrate production in people with ME/CFS goes down. Microscopic view of gut microbes from a woman sleeping

As many as 2.5 million Americans live with myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS for short. It’s a serious disease that can often arise after an infection, leaving people profoundly ill for decades with pain, cognitive difficulties, severe fatigue, and other debilitating symptoms.

Because ME/CFS has many possible causes, it doesn’t affect everybody in the same way. That’s made studying the disease especially challenging. But NIH is now supporting specialized research centers on ME/CFS in the hope that greater collaboration among scientists will cut through the biological complexity and reveal answers for people with ME/CFS and their families.

So, I’m pleased to share some progress on this research front from two NIH-funded ME/CFS Collaborative Research Centers. The findings, published in two papers from the latest issue of the journal Cell Host & Microbe, add further evidence connecting ME/CFS to distinctive disruptions in the trillions of microbes that naturally live in our gastrointestinal tracts, called the gut microbiome [1,2].

Right now, the evidence establishes an association, not direct causation, meaning more work is needed to nail down this lead. But it’s a solid lead, suggesting that imbalances in certain bacterial species inhabiting the gut could be used as measurable biomarkers to aid in the accurate and timely diagnosis of ME/CFS. It also points to a possible therapeutic target to explore.

The first paper comes from Julia Oh and her colleagues at The Jackson Laboratory, Farmington, CT, and the second publication was led by Brent L. Williams and colleagues at Columbia University, New York. While the causes of ME/CFS remain unknown, the teams recognized the disease involves many underlying factors, including changes in metabolism, immunity, and the nervous system.

Earlier studies also had pointed to a role for the gut microbiome in ME/CFS, although those studies were limited in their size and ability to tease out precise microbial differences. Given the intimate connections between the microbiome and immune system, the teams behind these new studies set out to look even deeper into the microbiome in larger numbers of people with and without ME/CFS.

At the Jackson Laboratory, Oh, Derya Unutmaz, and colleagues joined forces with other ME/CFS experts to study microbiome abnormalities in different phases of ME/CFS. They matched clinical data (the medical history) with fecal and blood samples (the biological history) from 149 people with ME/CFS, including 74 who had been diagnosed within the previous four years and another 75 who had been diagnosed more than a decade ago. They also enlisted 79 people to serve as healthy volunteers.

Their in-depth microbial analyses showed that the more short-term ME/CFS group had less microbial diversity in their guts than the other two groups. This suggested a disruption, or imbalance, in a previously stable gut microbiome early in the disease. Interestingly, those who had been diagnosed longer with ME/CFS had apparently re-established a stable gut microbiome that was comparable to the healthy volunteers.

Oh’s team also examined detailed clinical and lifestyle data from the participants. Combining this information with genetic and metabolic data, they found that they could accurately classify and differentiate ME/CFS from healthy controls. Through this classification approach, they discovered that individuals with long-term ME/CFS had a more balanced microbiome but showed more severe clinical symptoms and progressive metabolic irregularities compared to the other two groups.

In the second study, Williams, Columbia’s W. Ian Lipkin, and their collaborators also analyzed the genetic makeup of gut bacteria in fecal samples from a geographically diverse group of 106 people with ME/CFS and another 91 healthy volunteers. Their extensive genomic analyses revealed key differences in microbiome diversity, abundance, metabolism, and the interactions among various dominant species of gut bacteria.

Of particular note, Williams team found that people with ME/CFS had abnormally low levels of several bacterial species, including Faecalibacterium prausnitzii (F. prausnitzii) and Eubacterium rectale. Both bacteria ferment non-digestible dietary fiber in the GI tract to produce a nutrient called butyrate. Intriguingly, Oh’s team also uncovered changes in several butyrate-producing microbial species, including F. prausnitzii.

Further detailed analyses in the Williams lab confirmed that the observed reduction in these bacteria was associated with reduced butyrate production in people with ME/CFS. That’s of special interest because butyrate serves as a primary energy source for cells that line the gut. Butyrate provides those cells with up to 70 percent of the energy they need, while supporting gut immunity.

Butyrate and other metabolites detected in the blood are important for regulating immune, metabolic, and endocrine functions throughout the body. That includes the amino acid tryptophan. The Oh team also found all ME/CFS participants had a reduction in gut microbes associated with breaking down tryptophan.

While butyrate-producing bacteria were found in smaller numbers, other microbes with links to autoimmune and inflammatory bowel diseases were increased. Williams’ group also reported an abundance of F. prausnitzii was inversely associated with fatigue severity in ME/CFS, further suggesting a possible link between changes in these gut bacteria and disease symptoms.

It is exciting to see this more-collaborative approach to ME/CFS research starting to cut through the biological complexity of this disease. More data and fresh leads will be coming in the months and years ahead. It is my sincere hope that they bring us closer to our ultimate goal: to help the millions of people with ME/CFS recover and reclaim their lives from this terrible disease.

I should also mention later this year on December 12-13, NIH will host a research conference on ME/CFS. The conference will be held in-person at NIH, Bethesda, MD, and virtually. It also will highlight recent research advances in the field. The NIH will post information about the conference in the months ahead. Be sure to check back, if you’d like to attend.


[1] Multi-‘omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Xiong, et al. Cell Host Microbe. 2023 Feb 8;31(2):273-287.e5.

[2] Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS. Guo, et al. Cell Host Microbe. 2023 Feb 8;31(2):288-304.e8.


About ME/CFS (NIH)

ME/CFS Resources (NIH)

Trans-NIH Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Working Group (ME/

Advancing ME/CFS Research (NIH)

Brent Williams (Columbia University, New York)

Julia Oh (The Jackson Laboratory, Farmington, CT)

Video: Perspectives on ME/CFS featuring Julia Oh (Vimeo)

NIH Support: National Institute of Neurological Disorders and Stroke; National Institute of Allergy and Infectious Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; National Center for Advancing Translational Sciences; National Institute of Mental Health; National Institute of General Medical Sciences


  • Katherine Snow says:

    Very interested in the gut bacteria research. I am a healthy and active 85 year old woman. Bladder (rarely
    occurs) is easy to diagnose and treat. Gut and bowel are more complicated. Don’t believe I have a serious problem, but any knowledge would be helpful.

  • konjoo lee says:

    CFS/ME is a condition in which the functions of the brain that control the respiratory, circulatory, nervous, digestive, and muscular systems are out of order. ME is a condition in which high uric acid causes gout-like pain in CFS conditions. When the brain loses control of the digestive system, functions such as bowel movement and absorption also fail, resulting in symptoms such as IBS-IBD. When this movement or absorption is broken, the growth environment of microorganisms changes. As a result, the distribution of gut microbes is altered. In other words, changes in the gut microbiome are not helpful in diagnosis or treatment.
    Accurate diagnosis of CFS requires that brain signals from the brain not be delivered to each organ. And the treatment also requires that the brain signal is normally produced and accurately delivered to each organ so that the organ operates normally.
    Brain signal failure is often caused by electromagnetic wave interference caused by invisible electromagnetic waves, radiation, and negative charges. Failure occurs in the brain itself or failure occurs at the neural network level.
    CFS/Long COVID is cured in about 2 weeks, and ME takes time to excrete uric acid, so it can be cured in about 3-4 months.
    These treatments go beyond the concept of modern medicine to treat diseases with drugs. In other words, electricity is out of order, so it is impossible with medicine forever. It is like a computer malfunction cannot be treated with medicine or injection.
    Instead, it is easy to fix the fault electrically, but it is possible to treat it.

  • Pete Dozois says:

    Medications specifically ppi’s and probable herbicides in food are the cause. Severe debilitating joint pain. 20 years I’ve been battling this. Always eating exasperate it’s symptoms.

  • Deborah Holcomb says:

    Thank you for the focus on ME/CFS. It is also exciting to see patients being taken seriously and research being done!

  • Philip B Campbell says:

    I have had CFS for more than a decade. Here’s a story that is relevant and supports the research. A few years ago I had a massive blood clot in the superior mesenteric vein, blocking the blood supply to the upper bowel. They surgically disconnected my stomach from the intestine to give the intestine a chance to recover (it was close). After four months of getting my nutrition by a pic line straight into a vein, my stomach was reconnected and I went back to eating food. My gut had had a four month holiday. This had to have changed the biome. As I recovered I eventually reached the same level of function I had before the blood clot. The interesting thing is that I continued to improve to the point that I began to dream about putting CFS behind me. In the four or five years since this I have lost some of the gains, but I am still in better shape than I was before the blood clot. Perhaps this is because my gut, though traumatized, had a reset of the biome.

  • Fahmida pathan says:

    Thank you for research about ME/CFS.We are waiting to see the research advances.

  • Robbi says:

    At my wits end, I googled “2023 HELP unknown debilitating symptoms I am slowly dying” and here I am. I told every specialist, including JHU, that there was something more than Crohn’s disease (i.e. plus extensive other diagnoses and tragic symptoms)!!!! Interesting article and I truly believe CFS finally explains what I could never put into words! It is why I literally have physically deteriorated, struggle with consequences of overdoing it, and since 2017, had to tap out of work and have been homebound (luckily with difficult explanation of accommodation to work from home)! I fought claiming disability beyond words!

    As an overachiever, ex-All American USNA swimmer, I have been grieving the loss of my physical prowess for years! I literally dream of being checked into a medical research facility to figure out WHY I am so physically limited in life! I feel I am slowing dying, and would 100% AGREE to donate my body to science (while alive)! ANY information towards answers, would be a GODSEND! PLEASE HELP GUIDE ME to a place where I can find a better quality of life! My sons deserve better from this single Mom! THANK YOU! Robbi

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