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Strong gut/microbiome link to Parkinson's - possilbe relevance to ME/CFS

Discussion in 'Other Health News and Research' started by Skippa, Dec 2, 2016.

  1. Skippa

    Skippa Anti-BS

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    Mel9, ljimbo423, Jo Best and 11 others like this.
  2. roller

    roller wiggle jiggle

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    yeah, viruses and bacteria search is so exhausted already, isnt it?

    happy happy happy to further ignore the elephant herd in that smaller and smaller room :)
     
  3. Skippa

    Skippa Anti-BS

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    @roller do you mind translating that into something I can understand please?

    Ps haven't seen you posting for a while :)
     
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  4. Fighttolive

    Fighttolive

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    How profound is this discovery? Maybe it will open the floodgates..didn't a major study break headlines not too long ago about CFS being caused by alter microbiome?
     
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  5. Fighttolive

    Fighttolive

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    Wasn't there some big CFS remissions from fecal transplants also? I've been eating other people's s**t my whole life, why stop now!!
     
  6. trishrhymes

    trishrhymes Senior Member

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    Seriously, I think it's really interesting. I don't think they're suggesting a mystery bug that if only they could find it we'd all be cured.

    Rather I think the stuff about the microbiota may be relevant to lots of illnesses because the balance of different good and bad microorganisms in the gut seems to effect things like whether the gut lining is 'leaky', ie lets through into the blood organisms that really shouldn't be there and perpetuating inflammatory states, and also it effects whether we absorb nutrients etc.

    I think it's a fascinating field and may well have implications for ME too.
     
  7. Skippa

    Skippa Anti-BS

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    Yes, I think it is all going that way, many answers may come from the gut.
     
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  8. Simon

    Simon

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    This looks really important to me, it's the first strong evidence linking the gut microbiome to a brain-based disease, and links in to Mady Hornig and Ian Lipkin's work on the microbiome in mecfs, which assumes a central role for the gut-brain axis. This new Parkinson's disease research even focuses on key role for microglia, which many researchers think could play a central role in mecfs.

    Original study in prestigious journal, Cell
    Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease: Cell
    The work is on a 'mouse model' of Parkinson's Disease (PD), genetically engineered to have high levels of synuclein, the protein that clumps into fibres in PD, mice that go on to develop PD. Except it turns out the don't get PD if reared in gerrm-free conditions where they have no gut microbiome (trillions of bacteria, but viruses and fungi too).

    Following up the observation that microbiota in PD patients differs from healthy controls, they added gut bacteria from humans with PD to these germ-free mice, which triggered both neuroinflammation and symptoms of PD. Adding gut bacteria from healthy humans has no effect.

    And adult mice with the PD-like disease have the conditioin improved by antibiotics that wipe out the microbiome, and the symptoms get worse again when the microbiome is added back.

    Intriguing, huh?

    OK, a critical difference with PD is that was already a proven link to the gut. As for mecfs, many PD patients have gut problems either leading up to PD or after onset. However, PD researchers have found the synuclein protein found in the brain, also clumps in the gut nervous system, the 'enteric brain'..

    Putting this is a wider context, there are big concerns that links between the gut and disease are simple association, rather than gut problems causing disease. The best evidence (that I know of) for causal role is in obesity and inflammatory bowel disease - both diseases the feature the gut in a big way (in both cases transplanting bacteria in mice models can bring on the disease, as for PD). However, this is the first case where gut issues are linked to a disease of the brain.

    I'm hoping Cell won't mind me using their excellent graphical abstract here since the whole piece is open access
    [​IMG]
    View the original here
     
    Last edited: Dec 2, 2016
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  9. Marco

    Marco Grrrrrrr!

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    IF this pans out it might at least address one concern I've had about all this microbiome stuff - i.e. - can we point to a single human disease where the microbiome can be unambiguously linked to the pathology?
     
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  10. Simon

    Simon

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    The study also provided evidence that it's particulary bacterial products - short chain fatty acids (SCFAs) that are responsible for the effect. They used germ-free mice (no gut bacteria) and added the short chain fatty acids which provoked symptoms and microglial activation, and alpha-synuclein aggregation, just like gut bacteria did. Adding heat-killed gut bacteria had no effect.

    So overall these findings move on from the observation of gut symptoms in PD patients, and differences in gut bacteria between patients and healthy controls, to showing a direct role for gut bacteria in a mouse model (probably at least in part mediated by bacteriall short chain fatty acids) in causing activation of brain immune cells, aggregation of alpha-synuclein proteins and Parkinson-like symptoms.

    Better explanation:
    Parkinson's disease 'may start in gut' - BBC News

    Background Parkinson's disease may start in the gut and travel to the brain | New Scientist
    Inflammatory bowel disease is another. But yes, it's an important finding for exactly that reason
     
  11. eljefe19

    eljefe19

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    May I suggest Mesalamine and a combination of supplements like L-Glutamine, Colostrum and Probiotics to improve leaky gut?
     
  12. Jo Best

    Jo Best Senior Member

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    In UK, the translational biomedical research strategy of the Invest in ME Research Centre of Excellence for ME began with the gut. The foundation study got underway in October 2013 investigating the possible role of leaky gut. They've been collecting samples from housebound patients and house-matched controls (to allow for the effect on the gut microbiome of shared environment between patients and healthy controls).

    They published a detailed literature review June 2016. Here is a summary by the lead author of the article - http://blogs.ifr.ac.uk/ghfs/2016/07/me-cfs-virome/ ETA extract -
    The full paper - Reference: Navaneetharaja N., Griffiths V., Wileman T., Carding S.R. (2016). A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), J. Clin. Med. 5, 55; doi:10.3390/jcm5060055

    The IiMER Centre of Excellence is based at Norwich Research Park, but the research involves other centres, such as UCL and Oxford in UK, and is in collaboration with colleagues such as Maureen Hanson (one of the IiMER-funded medical students spent three months at the Cornell Lab) and Mady Hornig (Mady led a meeting at Norwich October 2015). This is the page on the new Invest in ME Research website for this research - http://investinme.org/ce-gm-projoverview.shtml
     
    Last edited: Dec 2, 2016
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  13. voner

    voner Senior Member

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  14. Marco

    Marco Grrrrrrr!

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    Well yes and no. From what I've seen there's a current wave of studies that purport to associate the microbiome with various diseases and even suggest the microbiome may trigger or exacerbate autoimmune disease.

    The various manipulations in that Parkinson's paper at first sight do appear to support a causal relationship and a plausible disease pathway but there are other explanations. SCFAs are known to mediate inflammation (and have been suggested to be anti-inflammatory which seems counterintuitive wrt the Parkinson's paper).

    Smoking, drinking, fatty foods and a sedentary lifestyle are also known to affect inflammation and may exacerbate existing disease states. What we wouldn't then conclude is that these behaviours 'cause' the disease.

    I take the point that the presence of SCFAs is necessary to trigger alpha-synuclein aggregation in this mouse model - but they had to engineer the mice to have high levels of synuclein in the first place. Any source of inflammation might have the same effect.

    As for 'triggering' autoimmunity (not claim made in this paper), I'm sure our resident expert would have a view on that.

    All that said - it's interesting but I'm still not convinced (from what I've seen) that a disturbed microbiome can be shown to directly cause any chronic disease.
     
  15. Hip

    Hip Senior Member

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    I tend to agree. We know that when the vagus nerve senses infection / inflammation in the peripheries of the body (such as the gut), then this nerve signals to the brain, and the brain then responds by ramping up levels of neuroinflammation and immune activation in the brain (probably as a protective measure to try to prevent infiltration of the peripheral infection into the brain, I should think).

    So if you have an existing neuroinflammatory condition in the brain, any inflammation that exists in the gut is likely going to worsen the existing neuroinflammation, by this vagus nerve mechanism.

    Gut inflammation may perhaps come from gut dysbiosis, or from a mild chronic infection of the gut with some mildly pathogenic bacterial species. So if you have a neuroinflammatory conditions, it make sense to keep you gut as heath and as inflammation-free as possible.

    But that does not necessarily mean that gut inflammation is the initial cause of the neuroinflammation (although potentially the role of gut inflammation could be more complex, if we consider immune priming).



    In the best traditions of medical science, another study just published found the reverse: that short chain fatty acids (SCFA) were lower in fecal samples of 34 Parkinson's disease patients.

    (Possibly though, perhaps that could be because Parkinson's patients are absorbing the SCFAs into their body more, thus accounting for the lower amounts found in the feces. In which case, the two studies would align.)
     
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  16. natasa778

    natasa778 Senior Member

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    This is not really 'new' new. This came out over a year ago:


    Parkinson's disease begins in the gastrointestinal tract, large study indicates

     
  17. Hip

    Hip Senior Member

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    I don't really see that as "strong evidence".

    I think they are perhaps implicitly hinting that a virus or toxin from the gut can ascend the vagus nerve and enter the brain (this is possible, via a mechanism called axonal transport), and once in the brain it then causes Parkinson's.

    However, as mentioned in my earlier post, the vagus nerve can send inflammatory signals to the brain which worsen neuroinflammation. So this mechanism could also explain why those with vagotomy had half the risk of developing Parkinson's.
     
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  18. roller

    roller wiggle jiggle

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    from the OP... this means...

    - parkinson is highly contagious, obviously


    - no unusual pathogens in the infectious fecal sample found ?
    - not said what parasites/pathogens they tested it for ?
     
  19. hopeful2

    hopeful2

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    My mother had Parkinson's Disease. She had terrible digestive problems for years before being diagnosed with PD, including severe gastro paresis and even had a feeding tube for a time. One thing that has been noticed with PD patients is that they often had a high exposure to pesticides either as farmers or in their drinking water. When I was young the house we lived in was bordered by a farmer's field to the rear of our house and we had a well that was right on the edge of the farmer's field that provided our drinking water. I can remember the farmer regularly spraying the field with pesticides during the summer. I now wonder if the pesticides made their way into our drinking water and once in our gut killed off some of our microbes.

    I was diagnosed with CFS back in 1988 and I had terrible digestive issues for several years before being diagnosed. I have had bad flare ups of digestive issues ever since and am on a very limited diet because of it. Last year I had 2 very bad viruses early in the year and was given a course of antibiotics after each. One of the courses was a very strong antibiotic. Afterwards I had a severe flare of my CFS that landed me in the hospital. It has been nearly 2 years now and my bowels still are not back to normal. It would not surprise me at all to find out that the gut microbiome was intimately involved in ME/CFS.
     
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  20. Simon

    Simon

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    @Marco too. If I understand you right, you're saying that the mouse model is simply susceptible to inflammation, and any source will do?

    A couple of observations on that:
    1. There are already plenty of studies linking the gut and microbiome to PD, so they didn't just do a study and say "ha, that's the answer' and I think that needs to be factored in to any interpretation
    2.
    Smoking strongly reduces the risk of PD, suggesting that generic inflammation doesn't trigger PD.

    Ha, interesting.

    Overall, I think this is quite good evidence for a direct role of the microbiome in PD, but I agree it isn't definitive.
     

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