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The Role of Toll-Like Receptors In CFS/ME: A Promising New Therapeutic Approach?

Discussion in 'Latest ME/CFS Research' started by shannah, Mar 27, 2015.

  1. shannah

    shannah Senior Member

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    Courtesy of Jan Van Roijen
    Research from Italy

    Anyone have access to the whole paper or know of the therapeutic approaches they're referring to?

    Abstract
    Perturbations in immune processes play an important role in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), a multifactorial disorder mainly characterized by severe and prolonged fatigue and tipically affecting a variety of bodily systems including the immune system.

    Recent reports have shown that CFS/ME is an inflammatory disorder may be associated with autoimmune responses, mainly characterized by reduced functional activity of most immune cells, including neutrophils, natural killer cells, monocytes/macrophage and dendritic cells, together with dysregulations in cytokine levels, responsible for changes in the adaptive immune system.

    Interactions between gut microorganisms and host immune function have been shown to contribute to aberrant inflammation in CFS/ME patients.
 Commensal and/or pathogen-associated molecular patterns detected by Toll-like receptors (TLRs) expressed on intestinal epithelial cells appear to trigger inflammatory signaling cascade leading to neuroinflammation and neurodegeneration.

    This paper examines the role of TLR-mediated innate immunity in CFS/ME with evaluation of the current literature, also discussing about innovative therapeutic approaches represented by immunomodulators TLR-targeting.


    http://www.ncbi.nlm.nih.gov/pubmed/25808894
     
    Last edited: Mar 27, 2015
  2. adreno

    adreno PR activist

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    Of course they go directly to immunomodulators, instead of focusing on the gut dysbiosis.
     
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  3. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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  4. Bob

    Bob

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    Isn't that a chicken or egg question? i.e. which comes first? Gut dysbiosis or intestinal epithelial cell dysfunction? (BTW, I'm not sure this study is suggesting gut dysbiosis.)
     
  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Not a lot so far. This isn't really a journal. It is a place where people put ideas that they think somebody might invest money in for drug company projects. The abstract contains a lot of dogmatic introductory statements that look tendentious and no actual content. I am not sure why bacteria binding to toll-like receptors in the gut should cause neuroinflammation. It sounds like a word salad of trendy ideas to be honest.
     
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  6. adreno

    adreno PR activist

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    I don't understand it as bacteria binding directly to the TLRs. But bacteria can regulate the expression of TLRs. Wouldn't this have an effect on inflammation?
     
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  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    They say bacterial molecular patterns being detected by TLRs - which means bacteria binding to TLRs to my understanding. I cannot see how this makes your brain unhappy. And gut epithelial cells are normally exposed to shedloads of bacterial molecular patterns. Maybe in the article there is a novel or plausible idea but this looks to me like rent-a-hypothesis!
     
  8. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    It seems consistent with a lot of studies I've read on interactions between the gut microbiome and the immune system, although I admit I don't have an in-depth understanding of this. I'd love to see the full text.

    EDIT: the phrase "evaluation of the current literature" suggests that it is to some extent a review, which seems worth a read.
     
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  9. Marco

    Marco Grrrrrrr!

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    You're probably right about the rent a hypothesis but isn't LPS often used in models to induce neuroinflammation?
     
  10. adreno

    adreno PR activist

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    It is, and activation of TLR4 increases intestinal permeability and endotoxins in plasma. See:

    http://www.ncbi.nlm.nih.gov/pubmed/22906518
     
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  11. adreno

    adreno PR activist

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    You are right about this:

    http://journal.frontiersin.org/article/10.3389/fimmu.2013.00512/full
     
  12. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I am sorry but I cannot make head or tail of any of this really. If you simply think in terms of 'if this goes up that goes up and that goes down' you can build any hypothesis about inflammation you like, and you can always find a transgenic mouse that will illustrate it. But a story about a human disease has to have the right sort of beginning, middle and end in relation to primary causal factors, plausible feedback mechanisms and specific clinical result. As far as I can see the psychiatrists have decided to play with these pathways in the lab because it is trendy and they can get grant money but in terms of real human illness it makes no sense whatever. I may be wrong but I have been in this game a long time. The microbiome is trendy in everything, including RA, but I have yet to see anything that makes sense come out of studying it, other than the very specific and atypical case of Helicobacter.
     
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  13. Crux

    Crux Senior Member

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    As an anecdote ; I can induce neuritis, and a shingles outbreak, simply by having a serving of naturally fermented food, a probiotic, or anything with commensal bacteria.

    I realize all food is teeming with microbes, so the 'dose makes the poison', in my case.

    Since the shingles, herpes zoster virus, resides in my spine, and my symptoms are neurological ; I believe that commensals can cause neuroinflammation in some people.

    I'm only one example, but I suspect this is happening to many folks, especially those with ME/CFS. ( Lactic acid has been found in the CSF of people with MS. Some people with Parkinson's have been found to have SIBO.)
     
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  14. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    My understanding of 'commensal bacteria' or 'commensal microflora' is the micro-organisms present on and in our bodies, as described here. They are essential to our survival.
     
  15. Crux

    Crux Senior Member

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    Yes, commensal bacteria are essential, and symbiotic with us as their host.
    Although,if their numbers are overgrown, then they can become infectious and inflammatory.

    A search for reports regarding infections from many types of commensals is pretty easy to find.

    Edit: I hope this doesn't seem snarky, apologies if so.
     
    Last edited: Mar 27, 2015
  16. thegodofpleasure

    thegodofpleasure Player in a Greek Tragedy

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  17. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    No problem. As you can see from some of my blogposts, e.g. this one, the role of the gut in ME/SEID is an area of great interest to me.
     
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  18. adreno

    adreno PR activist

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  19. Sea

    Sea Senior Member

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    Interesting Crux. Also, I've heard parents of kids with PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) say that their child reacts with a flare of symptoms to some or all strep family probiotics
     
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  20. Crux

    Crux Senior Member

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