New research: gut microbes identify 83% of patients

Signs of bacterial infection and inflammation

Recently, a team of researchers led by Ludovic Giloteaux of Cornell University measured the levels of several biomarkers in 49 ME/CFS patients and 39 controls, including LPS to measure bacteria in the bloodstream and CD14 and C-reactive protein to measure inflammation.  Researchers also measured the levels of intestinal fatty acid binding protein (I-FABP) to show GI damage.
ME/CFS patients showed significantly higher levels of lipopolysaccharides (LPS) in their blood, which means that they had more gram-negative bacteria than controls. These elevated levels of bacteria then caused the liver to produce LPS-binding protein, which was also elevated above levels found in controls. sCD14 is one of the ways that the body senses invading bacteria.  Levels of this inflammatory marker are high in those experiencing severe bacterial infections.  CD14 levels were also high in ME/CFS patients.

Microbial diversity

Giloteaux found that “ME/CFS samples had a significant overall lower microbial diversity, [which] differed at the phylum and family levels”: ME/CFS patients had especially low levels of Firmicutes in comparison to controls, and higher levels of Proteobacteria.
Proteobacteria include a wide range of pathogens, such as Escherichia, Salmonella, Helicobacter, and Yersinia.  Firmicutes are the largest group of bacteria in the human gut, and include Clostridium, Bacilli, and Ruminococcaceae.  ME/CFS patients were low in Ruminococcaeaea in particular, which has been associated with poor gut health, and low in Bifidobacterium, which is often used as a probiotic.

By using both inflammatory markers and the microbiome ‘blueprint’ of the disease, researchers found they could identify 83% of patients.

Microbiome as biomarker

The coupling of increased inflammatory markers plus dysbiosis led the researchers to conclude that damage to the gut is leading to microbial translocation, or the movement of bacteria from the inside of the gut to the bloodstream.  This in turn could lead to more inflammation and greater immune dysregulation.  While Giloteaux and his team did not claim to have found ‘the answer’ to ME/CFS, they may have identified a series of biomarkers: by using both the inflammatory markers and the microbiome ‘blueprint’, the researchers found they could identify 83% of patients.

More evidence

This is far from the first study to identify microbial dysregulation in ME or CFS patients — it’s not even the first to identify dysregulation in Firmicutes populations in particular.
In 2015, S.K. Shukla and colleagues examined blood and stool samples taken after patients and controls had exerted themselves. They found that both blood and stool sample microbiomes differed in ME/CFS patients (defined using the Fukuda criteria) in the abundance of “several major bacterial phyla”, including Bacilli in blood 48 hours post-exercise and Clostridium XIVa and IV (Firmicutes) in blood samples collected 15 minutes after exercise.  Moreover, the relative abundance of Firmicutes to Bacilli was skewed high in ME/CFS patients.
Other studies have verified dysregulation in the intestinal microbiota in ME/CFS. For example, a study of Norwegian ME patients demonstrated an increase of Firmicutes in patients over controls, including a fifty-fold decrease in Holdemania, and a 20-fold increase in Lactonifactor.

A piece of the puzzle

The gut microbiome plays a crucial role in human health, as 70% of the immune cells of the body live in the gut.  Healthy digestion supplies nutrients, produces beneficial or toxic metabolites and waste products, and destroys – or does not destroy – ingested pathogens.  The gut microbiome can also play a vital role in endocrinology by helping to generate and/or stimulate release of dopamine, norepinephrine, serotonin, nitric oxide, and the inhibitory transmitter aminobutyric acid — the gut bacteria may even directly affect the vagus nerve.
All this means that the gut microbiome could be a central key to unlocking the pathology of ME and CFS.
In the era of the metagenome, efforts to understand chronic disease have forced a shift from reliance on a ‘‘one microbe, one disease’’ model to a focus on how entire populations of microbes can become dysregulated. It is more likely that the structure of entire communities of microbes shift in individuals as they become ill, rather than that one pathogen is to blame.
For a more in-depth review of evidence of microbiome involvement in ME/CFS, see Navaneetharaja et al’s A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)? in the Journal of Clinical Medicine and check out MEpedia’s page on the microbiome.

[Edit!] If you’re interested in the microbiome’s effect on human health, a new text is coming out in October with a whole chapter devoted to gut dysbiosis and its relation to CNS disturbances. While this author can’t attest to the quality, it does look interesting! The Human Microbiota and Chronic Disease: Dysbiosis as a Cause of Human Pathology by Brian Henderson, Luigi Nibali.


8 thoughts on “New research: gut microbes identify 83% of patients”

  1. It’s great that these biomarker levels could potentially identify ME/CFS patients against healthy controls. Though I’d be curious to know what other groups might be similarly identified by their gut biome. Could ME/CFS be distinguished from Fibro, Chronic Lyme, or even MS, for example; or within different “subgroups” of CFS? Also, if Fukuda criteria are being used, are they really looking at true ME/CFS?

    1. I believe they were looking at Fukuda. I think it would be really interesting to see comparisons between ICC ME and Fukuda CFS, as well as healthy controls.
      You make a good point, Amy, that I hadn’t considered. Are we looking at ‘chronic gut dysbiosis’ or are we looking at something more specific? I wonder how this data would compare to other chronic illnesses where gut dysbiosis plays a role.

  2. Thank you for this summary! Informative, comprehensible, sticks to facts! =)
    Two points: it seems the presence or absence of certain gut bacteria could be an easily done confirmatory test for ME?
    Secondly it would be interesting to know rather this amount of microbial abnormality is present at illness onset or is something which gets more and more altered with time and/or symptom severity?

    1. I do think they’re hoping to find a biomarker test. I think they may have run into problems using Fukuda, for which the patient population may be too heterogeneous to ever get a better than 4 of 5 likelihood of diagnosis — which is still very good! However, if they used ICC criteria, they might’ve been able to get closer to the mark, since this is a less heterogeneous group of patients.
      It would be really interesting to see if patients who match CCC or ICC can be identified more closely, and how they compare to those who fit Fukuda only…

  3. I wonder how many CFS/ME sufferers have had GI infections prior to getting CFS. My son had E Coli severely 2years before starting CFS symptoms.

  4. Better still, if they have found this issue, what can we do to help fix it? My tummy is killing me…any suggestions?

Comments are closed.

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