The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) (König et al, 2022)

Consul

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The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Authors:
Rahel S. König
Werner C. Albrich
Christian R. Kahlert
Lina Samira Bahr
Ulrike Löber
Pietro Vernazza
Carmen Scheibenbogen
Sofia K. Forslund

Abstract
Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

The study: https://www.frontiersin.org/articles/10.3389/fimmu.2021.628741/full
 

perrier

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Their working thesis is: "Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS." Certainly, here we can outline massive use of antibiotics starting in the pre teen years. Dr. Borody did a small study with patients doing Fecal transplants. But there really has not been much movement in this area. Why?
 

ljimbo423

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Their working thesis is: "Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS." Certainly, here we can outline massive use of antibiotics starting in the pre teen years.
This is one of the things they think can cause or contribute to ME/CFS.

I too had many rounds of antibiotics, for many things before I was seventeen. When I was 17 I developed ME/CFS.

Dr. Borody did a small study with patients doing Fecal transplants. But there really has not been much movement in this area. Why?
I think funding is a big reason.

There are some researchers working on it like Derya Unutmaz, M.D, but the gut microbiome and how it effects the immune system, brain, etc, is so vastly complicated, research has really just scratched the surface.

That's not to say a breakthrough couldn't come at any time though.
 

Consul

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Their working thesis is: "Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS." Certainly, here we can outline massive use of antibiotics starting in the pre teen years. Dr. Borody did a small study with patients doing Fecal transplants. But there really has not been much movement in this area. Why?
There is a study going on in norway called "The comeback study" where they try fecal transplant on 80 patients. I think results will come in 2023.

This is a single-center stratified (on gender and donor), block randomized, placebo-controlled, parallel group trial with 12-months follow-up of 80 chronic fatigue syndrome/encephalomyelitis (CFS/ME) participants. Participants will be randomized to treatment by preprocessed thawed donor fecal microbiota transplant or preprocessed thawed autologous fecal microbiota transplant. Primary endpoint is the efficacy of FMT at three months by the Fatigue Severity Scale. The investigators will use patient reported outcomes for primary and secondary outcome measures.

Previous studies suggest that a dysbiosis of the gut microbiota may be a key feature in CFS/ME. We hypothesize that

A: CFS/ME is caused by a dysbiosis in the gut flora causing barrier leakage of bacterial products, a low grade systemic immune activation and disturbances in the host energy metabolism.

B: Recovery of a normal gut flora by fecal microbiota transplantation (FMT) alleviates symptoms and may even induce remission of CFS/ME.

This project aims to determine if there is a true cause and effect relationship between a dysbiotic gut flora and CFS/ME by testing if treatment of the observed dysbiosis by FMT also can resolve CFS/ME symptoms. In this process, collection of blood, fecal, and urine samples before and after FMT will open the possibility to explore the relationship between the gut flora, immune response, host energy metabolism and CFS/ME using technologies of microbiomics, metabolomics and immunological characterizations for a better understanding of the pathobiology of CFS/ME.
https://clinicaltrials.gov/ct2/show/NCT03691987
 

Consul

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I too had many rounds of antibiotics, for many things before I was seventeen. When I was 17 I developed ME/CFS.
I have no idea about "early life" but i used alot of antibiotics in my early 20s and got me/cfs in my late 20s.

It's a very interesting subject @Consul and if I could pick one possibility I'd go for increased gut permeability as the thing to target.
I have been wondering if thats why meditation has improved my health to some degree, stress can apparently increase intestinal permeability.
 
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keenly

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This is one of the things they think can cause or contribute to ME/CFS.

I too had many rounds of antibiotics, for many things before I was seventeen. When I was 17 I developed ME/CFS.



I think funding is a big reason.

There are some researchers working on it like Derya Unutmaz, M.D, but the gut microbiome and how it effects the immune system, brain, etc, is so vastly complicated, research has really just scratched the surface.

That's not to say a breakthrough couldn't come at any time though.
SAME!

Before I ever used antibiotics I was so fit and healthy, never sick or off school even for a day!
 

bertiedog

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I also had a fair amount of antibiotics from childhood because of throat infections every winter and once in my 20s very frequent UTIs but I didn't develop real ME/CFS until I was 50. However I did have 2 weeks of flu in 1979 from which I found it difficult to recover and this started off severe vertigo attacks/migraines that meant I was bedridden for short frequent periods up until I developed ME.

So basically my health never really recovered after 1979 but I was able to lead a more or less normal life until 2020.

Pam
 

ljimbo423

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However I did have 2 weeks of flu in 1979 from which I found it difficult to recover and this started off severe vertigo attacks/migraines that meant I was bedridden for short frequent periods up until I developed ME.
Explaining how viral infections can trigger ME/CFS, for me, is the biggest hole in the gut microbiome theory as a cause of ME/CFS, although I do think the gut is a major cause. I have read about a couple of possible explanations.

One is the "gut-lung axis". Which is being researched a lot more since Covid 19 has come around. Essentially, as I understand it, they say that when someone gets a respiratory infection, the lungs send messages to the gut, that can cause or worsen dysbiosis and/or leaky gut.

The other possibility I think about, is viral infections causing "primed" or "sensitized" microglia in the brain. This is what ME/CFS researcher Jarred Younger thinks is happening.

Then he says, it would take very little stimulus to cause them to fully activate, triggering the sickness response like fatigue, nausea, malaise, aches and pains, etc.

If microglia are "primed", and someone already has even a mild leaky gut from too many antibiotics, etc. Then even a small increase lipopolysaccharides (which provoke a strong immune response) in the blood from the gut, could trigger the microglia in the brain, activating the sickness response and causing symptoms.