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Gut dysbiosis in severe mental illness and chronic fatigue: a novel trans-diagnostic construct? A systematic review and meta-analysis, Safadi, 2021

Discussion in 'Psychosomatic research - ME/CFS and Long Covid' started by Sly Saint, Feb 9, 2021.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    refers to 'chronic fatigue' throughout but then says
    https://www.nature.com/articles/s41380-021-01032-1
     
    Last edited: Feb 9, 2021
  2. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I've had a very brief look at this:
    "Zonulin is a tight-junction protein and key regulator of intestinal permeability, with increased circulating levels suggesting a compromised intestinal barrier [6]". OK sounds interesting but I wonder if this suggests you should expand they type of [blood proteomics] test Maureen Hanson published recently i.e. to try to establish whether there is a potential link to this protein or indeed other proteins.

    "autoimmune root has been suggested for CFS. Gut dysbiosis and structurally distinct endotoxins have been shown to trigger autoimmunity [57, 58], with downstream consequences of neuroinflammation [5, 59] and clinical phenotypes of sickness behavior."

    B-cell autoimmunity seems to be less likely i.e. since rituximab (which kills B-cells) didn't work [Fluge & Mella].

    T-cells still seem to be a candidate but, if I understand it correctly, that's disruption/auto-reactivity --- rather than autoimmunity [https://www.s4me.info/threads/the-p...reactivity-in-me-cfs.18640/page-3#post-318032]


    Derya Unutmaz was looking at MAIT (T-cells); in the context of a disrupted gut barrier in ME. I don't know what's happening/happened with that research.
     
  3. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    It looks like another robotic word salad to me.
    That opening sentence looks nonsense and isn't even grammatical.

    Reduced gut-microbial diversity (“gut dysbiosis”) has been associated with an anhedonic/amotivational syndrome (“sickness behavior”) that manifests across severe mental disorders and represent the key clinical feature of chronic fatigue.
     
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  4. Midnattsol

    Midnattsol Moderator Staff Member

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    Too tired to read and comment now much now, but if they are calling zonulin a tight junction protein that is not correct. Zonulin can regulate TJP expression and organization at the cell membrane, but it is not itself a TJP. It's produced many places in the body and is associated with various issues. In the gut it seems it will increase following gluten exposure in sensitive individuals, and may partly explain non-celiac gluten sensitivity.
     
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  5. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I'm laughing --- I was hoping you'd review it - the laugh was a bonus - thanks.
     
  6. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    There's a lot of truth to this in my opinion. I apologize in advance for giving such a disgusting and explicit description of what this is based on: I tend to have episodes of diarrhea with coincide with bad mood and generally feeling intensely unwell. Once the last load of diarrhea is expelled, I quickly start feeling better. There must be something in the gut that causes an ongoing reaction until it's expelled.

    One time by sheer luck I've had zonulin tested during a flare of particularly bad gut symptoms and it was high, about 4 times the upper limit of the normal range.

    This is I think proof of concept that "gut inflammation" for the lack of a better term can have strong effect on mood. To what degree this is relevant for mood disorders is not clear but it seems like a valid idea to explore further.
     
    Last edited: Feb 9, 2021
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  7. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

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    Looks like the CFS data in this meta-analysis consists almost solely of the paper by Giloteaux et al. 2016 (and some papers by Maes which I have my doubts about).

    So it might be more useful to simply read that paper.

    Giloteaux L, Goodrich JK, Walters WA, Levine SM, Ley RE, Hanson MR. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/ chronic fatigue syndrome. Microbiome. 2016;4:30
    By combining results from different illnesses, the results look more impressive than when you take each separately (which seems to me to be the more reasonable approach).
     
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  8. Andy

    Andy Committee Member

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    An ME Association post today.

    Code:
    https://www.facebook.com/meassociation/posts/3763463213711309


    I reckon if you have to go through that kind of experience then it would certainly affect your mood, even if there wasn't anything else at work affecting it. I've had similar experiences and it's not a fun time.
     
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  9. Mithriel

    Mithriel Senior Member (Voting Rights)

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    When I crash, my insides shut down but it is in the same way everything else slows down, my thinking included. It is no wonder that our systems are out of kilter when everything starts up again.

    Maybe it causes gut dysbiosis but it seems back to front. The sickness behaviour if such a thing exists or, more realistically, the relapse, causes gut problems.

    So getting sick causes sickness behaviour?
     
  10. Andy

    Andy Committee Member

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    My understanding is very much that, as you say, getting sick causes sickness behaviour. It's only people with false illness beliefs who believe that it works the other way around.
     
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  11. Penelope McMillan

    Penelope McMillan Established Member (Voting Rights)

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    I have Ulcerative Colitis and when that is flaring, I have massive, debilitating fatigue.
    It is nothing like ME 'fatigue' at all. It's a pure fatigue, not complicated by other symptoms. In fact, when I do nothing because of my UC fatigue, my ME symptoms reduce, due to the extra resting.

    So on a simple experience of just me, it makes sense to me that gut dysbiosis might be associated with fatigue.
    But I am also very clear that fatigue from my gut is NOT the same as what I experience with ME, ever.

    That word fatigue has a lot to answer for. It's like pain - one word to mean many things. Leading to research and articles that are a nonsense because they are not clear enough about what it is they are discussing.
     
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  12. Woolie

    Woolie Senior Member

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    I'm actually really surprised this paper got published, because it seems to have no proper overarching rationale. Why were these particular diseases singled out and not others?

    I'm not saying people with these diseases don't have gut problems. But the group choice just seems so random. Wouldn't it be helpful to compare those illnesses for which the disease process is better documented, wouldn't that be a better way to get a handle on whether the gut abnormalities are cause or effect? My guess is, if you take any sample of people who are unwell in some way, and you'll get these kinds of generic effects.

    They have attempted to draw all the illnesses together as being somehow related to "sickness behaviour", but that seems to be so loosely interpreted, anyone with any chronic illness would qualify. Terms like "sickness behaviour" and also "stress" seem to give licence to all types of science crimes, like glossing over important differences and inappropriately generalising findings from one domain to another entirely different one. We would be better off - and less muddled overall - if we banned them from the dictionary altogether.

    And in fact, for all their talk, these authors don't actually examine any measures of "sickness behaviour" at all. All the analyses look at things like overall symptom severity in the different diseases. Its like the sickness behaviour is some sort of marketing hook.

    Its become fashionable to call the kinds of nonspecific findings they report here "transdiagnostic", but I think this elevates them to a status they don't deserve (it implies something about how they represent common underlying features of all psychiatric disorders). Better to call them nonspecific observations. They may or may not mean anything.
     
    Last edited: Feb 16, 2021
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  13. Mithriel

    Mithriel Senior Member (Voting Rights)

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    The first time I heard of sickness behaviour was many years ago in the context of why some animals isolate themselves and hide when they get ill. It is a valid area of study but over time it appears to have been hijacked by BPS ideas so rather than a set of instinctive evolutionary responses it has become wanting to behave as if you are sick. Also the idea, without any evidence, that the behaviour continues even when the disease had gone which is used to back up pre existing theories.
     
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