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Assessment of intestinal tight junction proteins in Chronic Fatigue Syndrome

Discussion in 'Latest ME/CFS Research' started by M Paine, Mar 16, 2016.

  1. M Paine

    M Paine Senior Member

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    This paper seems to have been missed (I coudn't find it here, apologies if this is a repost).
    Perhaps that's because this paper is a conference paper that reports negative results. Negative results are still informative, in this case very much so if you are interested in the topic of gut permiability...

    Assessment of intestinal tight junction proteins in Chronic Fatigue Syndrome

    Rachel J. Passmore, E. W. Brenu, S.B. Ramos, S. Marshall-Gradisnik, N. Wong, S.L. Hardcastle, S. Johnston, A. Hawthorn, T.Nguyen, T.K Huth


    National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, Griffith University, Parklands, Queensland, Australia.


    ResearchGate link (PDF of full paper is available for download)


    "The aim of this study was to determine whether the gastrointestinal symptoms in CFS are caused by increased permeability in tight junctions resulting in subsequent translocation of pathogenic bacteria into the lumen. Serum concentrations of the intestinal proteins zonulin, LPS, and FABP2 were examined in CFS patients and healthy controls."

    "As increased tight junction permeability has been implicated in the pathogenesis of other fatigue associated diseases, where the translocation of pathogenic bacteria out of the intestinal mucosal layer causes an inflammatory response [5,8,9], it is reasonable to conclude that it may also be implicated in the aetiology of CFS. However, as these were no significant differences in the concentrations of any of the tight junction proteins measured, this suggests that increased permeability and subsequent translocation of bacteria into the lumen may not contribute to the pathogenesis of gastrointestinal symptoms in CFS. In addition, further classification of CFS patients based on gastrointestinal symptomatic criteria may be beneficial to further understanding the role of the tight junctions in CFS."
     
    Last edited: Mar 16, 2016
  2. M Paine

    M Paine Senior Member

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    I wonder if anyone is pursuing research into other pathways which may be leading to tight junction permeability, such as auto-antibodies against the cellular receptor for zonulin.
     
  3. msf

    msf Senior Member

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    I would have a lot more confidence in this finding if they used the CCC (I can´t access the full paper, I assume they used Fukuda again though).
     
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  4. M Paine

    M Paine Senior Member

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    @msf Yep, Fukuda
     
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  5. kangaSue

    kangaSue Senior Member

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    My money's on remodeling of ion channel function because of gut inflammation as being the reason for intestinal permeability. The gut is in a constant flux of low grade inflammation in healthy individuals, for normal digestion the intestinal mucosal layer demands a three-fold increase in blood flow volume requirement. Preservation of skeletal muscle is of higher order importance so with the common low blood volume finding in chronic fatigue syndrome, if the flow is diverted away from the bowel during peak demand it creates a hypoxic environment in the gut mucosa layer and resultant inflammatory chain of events.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980675/
    [Breakdown of the mucosal barrier potentially leads to translocation of microbiota or their toxic products. Two promising plasma markers, reflecting translocation of bacteria or their products, are D-lactate and endotoxin lipopolysaccharide (LPS), which are metabolic products or components of the commensal bacteria of the gastrointestinal tract.]

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/
    [In fact, consequences of intestinal inflammation, even if mild, persist for weeks beyond the point at which detectable inflammation has subsided (for review see [73]). Thus, persistent changes in GI nerve function, resulting in dysmotility, pain, and gut dysfunction long after the resolution of the initiating inflammatory event could contribute to GI disorders observed in CFS.]
     
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  6. lansbergen

    lansbergen Senior Member

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    You got it but it is more complicated than anybody thinks.

    The chronic infection I suspect goes to the intestines regardless of port d'entree. Nowadays some researches can find it in animals in the mucosa at the beginning and the end of the digestive track. Tests are not ready for humans. Many are working on it but it will take quitt some time before it can be used in routine testing.
     
  7. Justin30

    Justin30 Senior Member

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    This makes sense.....

    The reason I say this is that only when a subject is stressed that translocation occurs.

    Stress via physical, mental or emotional stress.

    The only time I feel severe GI upset is when any of these three factors occur.

    The one thing that also I feel causes this is dyregulation of the ANS in the form of dysautonomia like mentioned in the above posts. But even when my dysautonia is bad I dont always have GI pain.

    So my guess at rest without Oi we probably have the same junctions as normal people yhe second we are put under stress this changes as a study released a couple months back showing 3x the amount of translocation of gut bacteria.

    Might I also mention that mass dysfunction found in ME has to due with issues of malabsorprion of vitamins, minerals, proteins, etc. This is why we have muscle wasting, detox problems, neurotransmitter problems, etc. Just what i think....there is a massive neurological component too
     
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  8. kangaSue

    kangaSue Senior Member

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    This is the same mechanism that results in runners getting gut ischemia after an endurance event (gut pain and diarrhea) which for them is usually short lasting because they don't generally have a problem with low blood volume causing slow reperfusion. Some do go on to develop ischemic colitis though.

    I have chronic intestinal ischemia (but not ME/CFS), getting diagnosed with that took years because there were never any inflammatory markers present in blood tests. Only a colonoscopy revealed the extent of inflammation and mucosa damage, to the point that the scope perforated the bowel.

    My G.I. chose to ignore a prior finding of bowel wall thickening on a CT scan, a finding I later learned is suspicious for possible intestinal ischemia, something to be aware of if you've had or need an abdominal CT scan for chronic gut issues.
     
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  9. wastwater

    wastwater Senior Member

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    Increased cytokines can make tissue leaky
     
  10. M Paine

    M Paine Senior Member

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    Does anyone have a link to the paper or papers which demonstrated this? I've often wondered how this was measured. And are there any working hypothesis into what mechanism is responsible for this? Does marrow slow down red blood cell production while in a state of inflammation? Is Iron being sequestered in response to (and potentially in absense?
     
  11. M Paine

    M Paine Senior Member

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    Do you have a link to that paper?
     
  12. jimells

    jimells Senior Member

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    This isn't for ME in particular, but refers to POTS, which many of us have. The full paper is readable and worth the time to do so.

    http://circ.ahajournals.org/content/111/13/1574.long


    I don't recall seeing this study before, but it looks interesting
    http://www.ncbi.nlm.nih.gov/pubmed/19469714
     
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  13. Snow Leopard

    Snow Leopard Hibernating

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    Despite the null result, I like this study better than some of their others from this group, for the fact that it had a novel hypothesis. I'd like to see more novel studies - we need to take the risk of having null results and do these sorts of novel studies.
     
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  14. Justin30

    Justin30 Senior Member

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  15. M Paine

    M Paine Senior Member

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    Right, I wondered if you were talking about that paper @Justin30.

    When you say "showing 3x the amount of translocation of gut bacteria", I think that the paper you referenced stops short of proving that. The paper provided a relative count of different bacterial species (more specifically their DNA), in which the relative abundance of certain phyla were more abundant, but it does not give any insight into the overall abundance of bacteria.

    Also worth mentioning, that the study isolated bacterial DNA sequences, not bacteria. This is not to say that the findings aren't highly suggestive of Bacteria in serum (or at least their cellular components), but it's worth being clear that the translocation of living Bacteria is not confirmed by that paper.
     
  16. Justin30

    Justin30 Senior Member

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    Look into the work of Dr. David Bell and Dr. Rowe

    The machine that measures blood volume is called a DAXOR. The old version of the test is a nuclear medigine test that takes up too 4 hours. The Drs I mentioned will hopefully give you an insight. Someone else may provide some links.

    Not sure about Bone Marrow

    They have found anemic cfs/ me patients i guess when they used to call low blood volume hypovolemia theres is a component. Dr Bell found low blood plasma and low red blood cell count. He doesnt know why, niether does anyone else.
     
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  17. Justin30

    Justin30 Senior Member

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    That 3 x the amount of translocation may have been incorrect but for some reason I wrote it their as I had recalled an article or piece of literature that states this..could have been the original prohealth article. When you read a lot thing can get mixed up.

    I just went back and read the article which states:

    There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls.

    How else would they test to determine if their were Bacteria in the serum? Why else would they say specicific bacterial phyla from the blood? how would you test the amount of phyla if not through a DNA test?

    You may know more, do you care to share?

    There have been some people recently that mentioned the use of Rafaximin and the significant benefits the experienced from it. This was another thread on PR.
     
  18. M Paine

    M Paine Senior Member

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    >but for some reason I wrote it their as I had recalled an article or piece of literature that states this

    Yes, fair enough. There's a lot of literature out there, I would be interested in any similar papers or articles about this if anyone has anything

    > high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS

    Yes, the quote that you mentioned raised some eyebrows, and confused a few people. They say that there were "high levels" of bacterial sequences, but the paper only includes relative numbers.

    If the relative figure is 10%, that could be as few as one sequence, or millions, dependent on the absolute abundance of bacterial sequences.

    There was a bit of discussion about that in the thread on that paper here -> http://forums.phoenixrising.me/inde...following-exercise-challenge-in-me-cfs.41889/

    There's an explaination of why the absolute sequence counts are likely not reliable here -> http://forums.phoenixrising.me/inde...-challenge-in-me-cfs.41889/page-4#post-679428


    >How else would they test to determine if their were Bacteria in the serum?

    I'm not sure exactly. Perhaps by cell culture, immunomethods (detecting specific antigens), mass spectrometry or other PCR methods.

    I often wonder about this, and if there is translocation of living bacteria, do they remain alive in serum? In the presence of a healthy immune system, perhaps these microbes do not survive the shift from the permissive intestinal lumen, into the hostile bloodstream.
     
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  19. Justin30

    Justin30 Senior Member

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    LPS in indicator of fragmemted parts of dead gram negative and positive bacteria floating freely in serum.

    From what I understand sepsis or septic shock is one way for high levels of LPS. The marker for LPS in Serum is Soluble CD13 as I assume this cytokine reacts in some way with LPS.

    I assume new GI studies from Lipkin and Co. will highlighy this more.

    Further there should be several new studies coming out this year around gut stuff...

    KDMs primary focus is GI issues and translocation and intercellular bacteria.

    I think this definition of sepsis or septic shock provides and makes a lot of sense if you think about GI issue and translocation leading to low levels of sepsis cause damage througout the body. Look specifically at the Pathophysiology. As gram positive and negative bacteria make up the whole microbiome.

    https://en.m.wikipedia.org/wiki/Septic_shock

    So if you believe in the GI theory it would make sense that low level sepsis may be the underlying factor to dysfunction.

    To add to this when the immune system can not clear the body of the extreme toxic burden of LPS, viruses, active bacterias it can be suggested that the body is under to much stress and the immune system becomes underactive. Essentially the macrophages stop running around and cleaning up everything effectively.

    This leads to all sorts of dyregulation, damage and sepsis....

    I dont know though.....no one does....
     
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  20. Justin30

    Justin30 Senior Member

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    I just wanted to add that ME/CFS is like cancer in my eyes. It does affect all systoms yes but does so differetly in everyone.

    ME/CFS will turn into many disorders GUT ME, MITO ME, BRAIN ME, CNS AND ANS ME, etc.

    Then I feel will be categorized in stages like cancer 1-4.

    As well can spread to other sustems just like how cancer does.

    Its just sad the medical community has turned a blind eye to people sick and dieing slowly in beds for 3 decades.

    Then you have PACE and Wessely that have hurt millions worldwide through GET....

    Anyways nice chat @M Paine

    Seems like you are up on all this stuff which is is nice to see....
     
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