Lipkin's Monster ME/CFS Study: Microbes, Immunity & Big Data
The Microbe Discovery Project outlines an ambitious new study by top researchers that has collected patient samples, but needs desperately funds to complete the work.
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The microbiome hypothesis: Lipkin's collaborative, part 1 (Simon McGrath blog)

Discussion in 'General ME/CFS News' started by Simon, Jul 17, 2018.

  1. Simon

    Simon

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    New blog at ME/CFS Research Review


    [​IMG]

    A gut reaction is the problem in ME/CFS – that’s the main idea being pursued by Dr Ian W. Lipkin of the Center for Infection and Immunity at Columbia University. He believes that the body’s response to changes in the gut could be what’s driving ME/CFS for at least some patients.

    Lipkin’s collaborative group, the Center for Solutions for ME/CFS, will test this theory as part of a $9.6 million, five-year research programme, which Lipkin was good enough to discuss with me via phone and email.

    This huge research programme, which is funded by the National Institutes of Health (NIH), is made up of three main projects. This blog looks at the first two, which will use high-tech approaches to see if changes in the gut are causing changes in the body, particularly in the immune system. The third project, which looks at the biological response to exertion in ME/CFS, will be covered in the next blog.

    ....
    Read the full blog
     
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  2. Simon

    Simon

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  3. percyval577

    percyval577 Senior Member

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    Maybe at any opportunities they also could have an eye on the other direction, eg that the immunesystem would drive/keep the gut microbiome for some purpose in some direction. The reason being that the microbiome produced a lot of stuff needed/utilizised by the body.
    (I personaly would opt for this - but probably more complicate to investigate - possibility.)
     
    Last edited: Jul 17, 2018
  4. ljimbo423

    ljimbo423 Senior Member

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    Thanks Simon, great info!:thumbsup::)

    I would just like to add that ME/CFS researcher Chris Armstrong also thinks the gut is driving ME/CFS-

    LINK

    So that's 3 leading ME/CFS researches now, that are publicly saying they think the gut is the driving force behind ME/CFS. Three and counting!:)

    My feeling is, that as the research continues to unfold, more researchers will be onboard with this hypothesis.

    Jim
     
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  5. Frenchguy

    Frenchguy Senior Member

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    The problem in US research (in general, not specific to ME/CFS research) is that they don't works properly on plausible physiological models based on currents data.

    NIH invests millions $ in differents centers. Theses researchers collect massive informations , put them in a computer and are sure that the response is here.

    I don't think it's the best way to resolve a problem. When we look at actual data on pubmed, we can see a lot of work (ok, many studies performed on oxford and Fukuyama criteria should be excluded).

    I like people like R.Phair because he presented an hypothesis based on data, which could explain many symptoms, and works to prove or disprove this hypothesis. He is Professor in biomedical engineering, and for now, it's the only who work on a plausible hypothesis.

    If researchers don't ask the right questions, for example, why people have light and sound sensitivity, why they have orthostatic intolerance, which mechanism could explain conceivably PEM, they risk to spending time and money for nothing.

    The company BM systems works on physiologicals models establishments for disease known incurable, or difficult to treat (you can see pdfs on their website). It's like machine learning like @mariovitali uses.
    http://www.bmsystems.net/ (@Ben H , in case it's interesting for Ron).
    They are working with French researchers to establish models. The goal is to perform additional tests to confirm or disprove theses models, and test treatments.

    It's possible that the gut can be a factor for some people (i myself have problems...). It's don't think studying the gut will lead to treatment (I don't know a disease in which the gut cause neurological, autonomic, PEM, and "brain pain" symptoms . Like in many disease, i think ME/CFS have entry points, but they have to find the way to cut the vicious circle, it's the more important for us.

    As French, I haven't to say that because Europe don't invest 1€ in research (i hope things are changing in France).
    If we look many diseases, researchers are working since decades on trying to find the causal factor, but they don't. They now treat mechanisms which allow disease's control.
     
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  6. ljimbo423

    ljimbo423 Senior Member

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    I don't think mitochondrial dysfunction and the gut being the driving force in ME/CFS have to be separate issues. I think the immune system activation and the oxidative stress from the gut, can cause the mitochondrial dysfunction seen in ME/CFS.

    I think that's what Chris Armstrong, Derya Unutmaz and Lipkin
    are saying too. That it's the gut causing the mitochondrial issues.

    I don't think research into the gut as the driving force behind ME/CFS, in any way discounts how important mitochondrial dysfunction is.

    This is a quote from Simon's blog explaining Ian Lipkins ongoing research-

    So Lipkin is also looking into mitochondrial dysfunction, even though he thinks the gut is driving ME/CFS.

    If immune system activation from the gut is causing low grade brain inflammation, which very plausible from the research I've done. The low grade brain inflammation, mitochondrial dysfunction and immune system activation, could explain most or all of the things you mention above.

    That's why the 5 teams from the ME/CFS collaborative and the 5 teams from Solve ME/CFS initiative (SMCI) are all focused on the gut, the immune system, the brain and metabolomics- (mitochondria).

    These four areas, if dysfunctional, could explain all of the symptoms of ME/CFS, in my view.

    The 5 SMCI teams are from all over the world.:) Sweden, Spain, USA, United Kingdom, Germany and Israel.


    LINK


    Jim
     
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  7. percyval577

    percyval577 Senior Member

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    :thumbsup::thumbsup::thumbsup:
    Neverthless, they might find something even without good searching questions.
     
  8. mariovitali

    mariovitali Senior Member

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    Everyone is looking at the Gut without looking at the Liver.

    This is going to be "fun"....

    EDIT : I am sorry to say this in such a way but i begin to feel at loss here.
     
    Last edited: Jul 17, 2018
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  9. Frenchguy

    Frenchguy Senior Member

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    I hope you can present your theory at EUROMENE Mario
     
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  10. Frenchguy

    Frenchguy Senior Member

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    I hope, like all ME/CFS patients, but chances are low. It's like if you want to fish a sardine with a hook sized a tuna,
     
  11. percyval577

    percyval577 Senior Member

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    Si. It´s stumbeling around. On the other hand science needs luck sometimes, you never know where you will arrive.
    btw: [Mn + any infection]:time -> iNOS (<)-> NO <-> ACh <- [fat, sugar]:time. You might hook what this is?
     
  12. Frenchguy

    Frenchguy Senior Member

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    You can search, if you don't know what to look for, you will not find. It's my view.

    I'm not doctor, researcher or biochemist. I worked in industry as engineer before get sick.
    When we worked on a complex and costly project, we generate differents hypothesis before working.
     
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  13. percyval577

    percyval577 Senior Member

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    Oui, you need ideas. Without ideas no evaluation of facts. More on the long run, without facts no ideas.
    The recent paper has found a correlation between severness of our disease and amount of microgenomics in the blood (or so, my mecfs brain, you know probably), including specific correlations.

    "In ME/CFS without IBS, decreased tyrosine correlated with decreased P. distasonis. Increased TG 54:6 A was correlated with D. formicigenerans and TG 54:8 was correlated with decreased B. caccaeand D. formicigenerans. Parabacteroides and Bacteroides species have the ability to convert complex polysaccharides into energy sources24. D. formicigenerans ..."

    It´s a trace and a great finding,
    maybe not already a good idea to propose: "gut ->strange disease". I find it rather unlikely.

    A more interesting idea is: gut<-usage of the gut, or as things like to be complex: gut<->usage of the gut.
    But now what for a usage? How many years do they have? Maybe something will develope if they manage to have fantasy.

    Without fantasy no ideas. Without ideas theory. Without theory no useful facts.
     
    Last edited: Jul 19, 2018
  14. percyval577

    percyval577 Senior Member

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    No, I have looked at the liver, and I have come to the conclusion that the arginase would be indirectly the first cause of our disease: Messages #17 and #29 ff. Accordingly I improve (very slowly though).
    Please read, especially if your difficult to understand program has come to a comparable conclusion.
    Manganese and arginine are key. Nitric oxide is central. Part of an equilibrium might be acetylcholine.
     
    Last edited: Jul 17, 2018
  15. Learner1

    Learner1 Forum Support Assistant

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    Immune system activation yes, but I doubt the gut is the main cause of mitochondrial dysfunction in all of us.

    I've identified different contributors to my mitochondrial dysfunction, some of which are genetic as well as others, none which involve the gut.
     

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  16. ljimbo423

    ljimbo423 Senior Member

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    I agree that there are many things that can cause or contribute to mitochondrial dysfunction.

    Such as mold allergies, drugs, genetics, epigenetics, high levels of heavy metals, high levels of pesticides or other toxins, etc.

    I feel like these things, if they cause ME/CFS, will be considered as "atypical ME/CFS" as research continues. My feeling is that a dysfunctional gut will be found to be "typical ME/CFS" or the primary cause of ME/CFS.

    I think that's where the research has and is leading and that's why there are a few leading ME/CFS researchers already, that are saying publicly that they are in agreement with the gut as the main driver of ME/CFS.
     
  17. Learner1

    Learner1 Forum Support Assistant

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    As they keep saying, there are many subsets. I do not believe there's such a thing as typical or atypical ME/CFS.

    Every single one of us has unique genes and environmental exposures that make us one of a kind.
     
  18. Hip

    Hip Senior Member

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    I think we might be able to rule out the idea that PEM is caused by bacteria leaking into the bloodstream by the following simple observation: ME/CFS patients who take corticosteroids can eliminate any PEM effects from exercise.

    Now corticosteroids are known to reduce the antiviral Th1 immune response, but increase the antibacterial Th2 immune response. This means that if the immune response to bacteria were the cause of PEM, then corticosteroids would likely make PEM worse, because they increase the antibacterial Th2 immune response.

    But we know corticosteroids ameliorate PEM, so that fact is evidence against the idea that PEM is caused by bacteria in the bloodstream.
     
    Last edited: Jul 21, 2018
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  19. Learner1

    Learner1 Forum Support Assistant

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    My PEM is ameliorated by glutathione and BCAAs, but not by hydrocortisone or dexamethasone.
     
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  20. ljimbo423

    ljimbo423 Senior Member

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    Yes they do in some people short term. A very, very few will have major long term benefits. Most people that take them for weeks, months or years, of which there are many here, get some minor to moderate improvements.

    Some are made much worse by corticosteroids. I am one person they make worse and there are others as well.


    Steroids also lower the TH2 response of the immune system not just the TH1 arm. Asthma is often TH2 dominant and steroids bring relief to many people with asthma.

    Lipopolysaccharides increase the innate immune system or TH1-

    LINK

    LINK

    I think the immune system dysfunction/exhaustion etc. in ME/CFS is very complicated.

    I think Chris Armstrong's, Derya Unutmaz's and Ian Lipkins hypothosis, that the gut is the primary driver in ME/CFS is right on the money. My feeling is they probably have more of the "inside" scoop than you or I do.:)
     
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