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Preprint: Deficient butyrate-producing capacity in the gut microbiome of [ME/CFS] patients is associated with fatigue symptoms, 2021, Guo,Lipkin et al

Discussion in 'ME/CFS research' started by Andy, Nov 1, 2021.

  1. Andy

    Andy Committee Member

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    Abstract
    Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, debilitating disease of unknown cause for which there is no specific therapy. Patients suffering from ME/CFS commonly experience persistent fatigue, post-exertional malaise, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever and irritable bowel syndrome (IBS). Recent evidence implicates gut microbiome dysbiosis in ME/CFS. However, most prior studies are limited by small sample size, differences in clinical criteria used to define cases, limited geographic sampling, reliance on bacterial culture or 16S rRNA gene sequencing, or insufficient consideration of confounding factors that may influence microbiome composition. In the present study, we evaluated the fecal microbiome in the largest prospective, case-control study to date (n=106 cases, n=91 healthy controls), involving subjects from geographically diverse communities across the United States.

    Results: Using shotgun metagenomics and qPCR and rigorous statistical analyses that controlled for important covariates, we identified decreased relative abundance and quantity of Faecalibacterium, Roseburia, and Eubacterium species and increased bacterial load in feces of subjects with ME/CFS. These bacterial taxa play an important role in the production of butyrate, a multifunctional bacterial metabolite that promotes human health by regulating energy metabolism, inflammation, and intestinal barrier function. Functional metagenomic and qPCR analyses were consistent with a deficient microbial capacity to produce butyrate along the acetyl-CoA pathway in ME/CFS. Metabolomic analyses of short-chain fatty acids (SCFAs) confirmed that fecal butyrate concentration was significantly reduced in ME/CFS. Further, we found that the degree of deficiency in butyrate-producing bacteria correlated with fatigue symptom severity among ME/CFS subjects. Finally, we provide evidence that IBS comorbidity is an important covariate to consider in studies investigating the microbiome of ME/CFS subjects, as differences in microbiota alpha diversity, some bacterial taxa, and propionate were uniquely associated with self-reported IBS diagnosis.

    Conclusions: Our findings indicate that there is a core deficit in the butyrate-producing capacity of the gut microbiome in ME/CFS subjects compared to healthy controls. The relationships we observed among symptom severity and these gut microbiome disturbances may be suggestive of a pathomechanistic linkage, however, additional research is warranted to establish any causal relationship. These findings provide support for clinical trials that explore the utility of dietary, probiotic and prebiotic interventions to boost colonic butyrate production in ME/CFS.

    Open access, https://www.medrxiv.org/content/10.1101/2021.10.27.21265575v1.full-text
     
    Last edited: Nov 1, 2021
    Lindberg, Michelle, FMMM1 and 12 others like this.
  2. Andy

    Andy Committee Member

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  3. Trish

    Trish Moderator Staff Member

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    My understanding of changes in microbiome is that the biggest influences on gut bacteria are taking antibiotics, and changes in diet. In which case I hope researchers find a way to take these into account.
     
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  4. Andy

    Andy Committee Member

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  5. Mij

    Mij Senior Member (Voting Rights)

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    My butyrate-producing bacteria were below normal on my test when I had h pylori infection.
     
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  6. Snowdrop

    Snowdrop Senior Member (Voting Rights)

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    I remember back before S4ME came into existence that many people were talking about a new supplement called Miyarisan? Meant to boost butyrate production. Many of us still seem to be around ME forums.

    But maybe it's not as simple as that. I hope that they have found something useful and that some kind soul will be able to explain that when the time comes.
     
    Michelle, Tia, JaneL and 5 others like this.
  7. strategist

    strategist Senior Member (Voting Rights)

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    The impact of butyrate producing bacteria is something that could be tested in a clinical trial. Should be relatively easy to do.
     
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  8. Creekside

    Creekside Senior Member (Voting Rights)

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    I think if it was an effective treatment for ME, someone would have noticed it after taking butyrate supplements. I've had different antibiotics and drastic diet changes, which should have affected my butyrate production, but I didn't notice any significant differences in my ME.
     
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  9. Hutan

    Hutan Moderator Staff Member

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  10. Hutan

    Hutan Moderator Staff Member

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    I was just looking through the threads tagged with butyrate and noticed this interesting one posted by @alicec:
    Extensive impact of non-antibiotic drugs on human gut bacteria (2018) Maier et al

    They screened non-antibiotic drugs taken by humans against a range of bacterial species in the gut microbiome. they found 27% of the drugs they screened had an antibiotic effect, including antipsychotics.

    They also found that human-targeted drugs had an impact on major butyrate producers:
    So, it gets very hard to unravel what is causing what.

    This Lipkin study only controlled for antibiotic use in the 6 weeks prior to sampling.
     
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  11. Kiristar

    Kiristar Established Member

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    Wonder if this might be one reason why FMT sometimes proves successful...?
     
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  12. Hutan

    Hutan Moderator Staff Member

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    Screen Shot 2021-11-02 at 12.05.47 PM.png

    I'm not sure how important the differences in abundances are - here are graphs from the paper for two key species. Green on the left is controls, red on the right is ME/CFS. There's a lot of overlap and the average isn't very different, even though the p value suggests a difference.

    Maybe it's worth carefully going through the paper, but I haven't.
     
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  13. Midnattsol

    Midnattsol Moderator Staff Member

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    The worst part is you could likely get adequate information about the diet for this type of study from a semiquantitative food questionnaire with foods that are known to feed the "positive" bacteria. So including starchy roots and tubers (maybe also how they are prepared as cooked + cooled down is most beneficial in this instance sine the cooling process make the starches into resistant starch that the bacteria enjoy), cruciferous vegetables, fodmaps, white or whole grain products, legumes, nuts, (fatty) fish, supplements (I would ask for omega-3's specifically, not just prebiotics) and maye some others but these were at the top of my head. By seeing if they are being eaten 1-3 times a day, 1-3 times a week etc you likely could see if the pwME have a different diet than the controls (and this is seen in many chronic conditions as preparing and eating food, not least shopping itself, takes energy the patient doesn't have).

    If doing a questionnaire like that is too much effort for the patient group (which could be the case here), there are online solutions that even provide pictures to illustrate different amounts of food, which possibly could be tailored so the participant could save and return to it later.

    People of different ages also often have statistically significant different intakes of various foods like starchy tubers, fish, vegetables in general.. :whistle:

    Even though more pwME than controls took prebiotic supplements, this does not mean they consumed more prebiotics overall. So I don't feel this is warranted:
    They write that no pwME were acutely malnourished, but not how this was screened for. Malnourishment in illness populations are not uncommon, especially not with energy limiting diseases. From my point of view, ME increases risk of inadequate dietary intake in line with other illnesses although I have never seen the illness on a list of "increased risk" illnesses. When in PEM I would fit neatly into the category of an "at risk patient" with neurological disease (trouble to shop, prepare and eat food due to low stamina/low energy/muscle weakness, low appetite, nausea).

    Less butyrate producing bacteria is not unique to pwME, and associations with between butyrate-producing bacteria and fatigue could come from the fact that the food that boost butyrate production also include numerous other beneficial compounds, which when low in the diet could contribute to fatigue. I am a fan of butyrate, I just don't like that this point often is not taken into account :)
     
  14. Andy

    Andy Committee Member

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    Peter Trewhitt likes this.

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