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9th Invest in ME International ME Conference, 2014 - Part 2: Pathogens and the Gut
Mark Berry continues his series of articles on the 9th Invest in ME International ME Conference in London, with the emphasis shifting from autoimmunity to pathogens and the gut ...
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All plausible causes of ME

Discussion in 'General ME/CFS News' started by redo, Feb 22, 2013.

  1. redo

    redo Senior Member

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    Excluding the misdiagnosed patients, I think it's safe to assume that most of the CCC diagnosed ME patients have at least one common denominator.

    In my opinion, the way to get the best clues as to what can lie behind this disease is to try to answer the following question. Pieces which must fit the puzzle:
    1) Mononucleosis, giardisis and the flu are among triggers for the disease. What can be triggered by so wildly different things such as the aforementioned infections?
    2) If the Mella/Fluge results hold true, that what, has to be able to cause symptoms mediated via autoimmunity/autoinflammation – further narrowing the list of possible suspects.
    3) The cause(s) leading to ME has to be more prevalent in women than men.
    4) What's causing the disease must be able to produce a wide array of symptoms (brainfog, joint paint, visual problems, fatigue etc).

    If you have any other things you'd like to add to the list, then please do weigh in.

    The only candidate I know of, which fulfills the four criteria, are ERVs. Does anyone else know of other viable candidates?

    I recently stumbled across these graphics from the company of which Perron works for. It pretty much falls in line with everything I've thought about how ME erupts: I find it really hard to believe that a exogenous retrovirus can be the culprit of the disease, when we know all too well how mononucleosis, giardisis or a flu (and more things which are pretty unrelated) can trigger the disease.

    [​IMG]

    (see an article about Perron's work here)

    I am hoping we can get a debate going about this in the weeks to come. I'm working on getting a list ready for early March, which will be discussed with a person who's got several hundred thousands of dollars disposable, which can be used for ME research.

    My health is really frail, so I wont pop by daily to the forums, but please do drop some lines if you've got some thoughts on the matter. Both on what pieces must fit the puzzle, and also on possible candidates matching that list.
    Waverunner, merylg, justy and 2 others like this.
  2. snowathlete

    snowathlete

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    point 3, I think, has to be significant. I've been puzzling over that for years.
    One thing I am thinking now in relation to HERVs is: which of them are on the X chromosome? If it was on the X chromosome then that would explain, perhaps, why it is more common in women. The same arguement would mean that it couldnt be on the Y chromsome (unless there was another copy of the same HERV elsewhere on a different chromsome - which is possible, I think).

    Check this paper out which looks at one on the X chromsome in MS patients (also over represented by females):
    http://www.retrovirology.com/content/8/S2/P54
    taniaaust1, merylg and redo like this.
  3. redo

    redo Senior Member

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    Yes, it's the chromosomes which makes the ERV hypothesis fit with point three. I have read some about that, but I haven't seen the article you linked to yet, so thanks for that, snowathelte!
    snowathlete likes this.
  4. alex3619

    alex3619 Senior Member

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    Point three is a major issue here. I suspect its mis-stated. What is significant is that more women than men get ME, but I am not sure about teens, I think in some studies there is a more even split? If so then this indicates that hormonal influences are involved in the final development of ME, and these might be different in teens and adults.

    I have explained numerous times why exogenous viruses can easily be the cause despite superficial evidence to the contrary. This includes retroviruses. These infections do not necessarily launch a full scale offensive right away. Its not just about incubation periods. Many viruses, and indeed many nonviral pathogens, can lurk for a long time. They go dormant, invade cells, slowly spread through tissue etc. So what is causing the issue may not be the trigger. If a dormant pathogen awakes and does the damage while you are injured, poisoned, or infected with another pathogen, then the issues surrounding the trigger are not particularly relevant to the cause.

    Personally I am leaning toward enteroviruses as a probable cause, but I wouldn't rule out the many causes / one disease concept either, or even many causes / several diseases. However it is not sufficient for such a pathogic infection to induce ME. I think other factors contribute. So its pathogen + risk factors + disease course, or at least thats my current leading hypothesis. So an entervirus might infect someone at age 10, then spread through muscles and gut, then at age 20 they get a bad case of whatever, and the enterovirus reactivates. In particular it will dump enterovirus (and this is true of other pathogens including herpes viruses) into any inflammed tissue.

    If the person has a connective tissue disorder this worsens the risk, as inflammation/infection in the gut, or even immune disturbances elsewhere as I hope to blog about later this year, can increase the risk of gut bacterial toxins crossing into the blood stream. That is not enough however. Unless the translocation is extreme, the liver should handle it. What would stop that? Not enough glutathione.So methylation issues might be involved, as might dietary choices and drug use such as NSAIDs especially paracetamol.

    I think, but cannot prove (its an hypothesis for now) that the LPS (lipopolysaccharide) family of bacterial toxins entering the blood stream in quantity triggers ME. I hope to blog about this in the last half of the year.

    The range of potential pathogens is high in my opinion. Its not primarily about the pathogen though, its about what the pathogen does in the body, and how the body reacts. There is a prevailing notion, which we know to be false (with numerous examples), that pathogenic infections have highly similar outcomes in different people. That is why common pathogens like entero- and herpes viruses have been dismissed, I think prematurely.

    I don't rule out a HERV however. Nothing in my interpretation is against HERVs as possible causes. This is particularly true for active HERVs in the intestines.

    Just to be clear, autoimmune/autoinflammatory processes are very much a part of the enterovirus hypothesis I outlined here.
    Sparrowhawk, leela, Persimmon and 6 others like this.
  5. Marlène

    Marlène Senior Member

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    My 50 cents:

    I think the terrain (= body) causes ME. We are all invaded by viruses and bacteria throughout our life.
    If for some reason you miss (x + y +z) then the virus and/or bacteria are able to proliferate again.
    Deficiencies in x, y and z are caused by genetics, stress and the virus/bacteria themselves.
    Hormonal changes are the pivotal point.

    People with genetic tendency to autism, ADHD and allergies are more prone to these deficiencies.
    taniaaust1 and merylg like this.
  6. Guido den Broeder

    Guido den Broeder *****

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    ME is triggered by enteroviruses. It is not an autoimmune disease.
    merylg likes this.
  7. Valentijn

    Valentijn Activity Level: 3

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    It can't be both? Viruses can trigger autoimmune disease.
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  8. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I have clipped the message I am quoting for brevity and clarity - hope this is OK and that it works!

    There is enough evidence connecting ME to leaky gut, and enough evidence for leaky gut leading to autoimmunity, and for ME being an autoimmune disease that, in my view, supports the causal link between the triggers you cite and possibly a multitude of others and ME being leaky gut. Infection can cause leaky gut. Viral, bacterial, perhaps fungal or parasitic, antigens - rather than toxins - entering the bloodstream through the leaky gut wall would be the next phase in this chain. This would trigger the production of antibodies against the particular antigens that are encountered. Then the immune system mistakes one of the body's own cells or molecules for the antigen because it carries a similar marker (epitope), and autoimmunity results.

    I've given links for the above 'complete theory of ME' in other threads and can post them here again if required.

    Other things can cause leaky gut too - the wrong food, chemicals, stress, etc.
  9. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I too tend to the theory that increased susceptibility in women may be hormonal rather than directly genetic.

    Here's one link which brings in LPS, as referred to by Alex3619, to the leaky-gut-autoimmunity theory:

    http://integrativehealthconnection....1/Leaky-gut-in-CFS-treatment-of-leaky-gut.pdf
  10. SaraM

    SaraM Senior Member

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    Rich VanK posted a list long time ago, but I can't find it using the search option.
  11. Jarod

    Jarod Senior Member

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    I have no clue.

    but will offer my two cents anyways....I agree with Rich Van K's research.

    Intuition tells me it is some kind of issue(genetic etc) that initially messes up the glutathione production. Lyme or a virus setting up the DNA problem, or maybe a ERV that lays and waits in all of us.

    A number of triggers can start the down hill snowball. Anything from fluoride, to metals, to pesticides, to drugs/medications, corn syrup, MSG, bacterial and viral, you name it.....

    The triggers generally attack the specific organ, but ultimately it boils down to the glutathione production in the liver? Each person has different set of symptoms based on their DNA modifications and particular environmental insults to organs that have succumbed. For instance, some people get sinus infections because they were smokers. Others get brain fog because the got lead poisoning. However it eventually boils down to most of us with glutathione and detox (liver type issues) where we can't detox, or kill the bacteria and viruses that invade our bodies.

    When we get sick, I think we are partly missing the bodies ability to absorb and utilize certain nutrients and cofactors. For instance some people needing maganese or sulfur. We have an impaired ability to absorb the nutrients due to the cells being so weak and obstructed.
    taniaaust1 likes this.
  12. snowathlete

    snowathlete

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    I look forward to reading your blogs Alex, they sound great!
    Maybe some others would flesh out their own hypotheses too...? If you care to write them, I'll care to read them!
  13. SilverbladeTE

    SilverbladeTE Senior Member

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    "All plausible causes"....hm...?

    I'm pretty sure we've really got Chronic F**kwit Syndrome.
    Decades of putting up with plonkers like Wesselly have burned out our adrenal glands and mutated us into the undead! GNASH GNASH! :p


    M.E. PATIENT AFTER 4 WEEKS OF GRADED EXERCISE TORTURE

    [​IMG]
    :alien:



    all joking aside, Alex's theory sounds good :)
    Scaldy, cigana, overtrain and 2 others like this.
  14. taniaaust1

    taniaaust1 Senior Member

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    What all those things do and the other ME/CFS triggers eg stress, surgery or whatever.. they all run the body down and could be making it vulerable to whatever else lurks inside of us.

    This theory would also explain ME outbreaks too.. maybe in those there is A DIFFERENT virus say a common one but more stronger then normal which goes throu affecting the whatever which the person ends up succumbing too (what has interested me is that many of the ME outbreaks have been described differently to one another but then maybe that is cause of whatever symptoms the dr or researcher was most interested in?).

    I dont have a set theory yet on all this, whether its just being caused by one thing or more then one thing working together.. but whatever it is.. I think MANY different factors end up being involved.
    redo likes this.
  15. Shell

    Shell Senior Member

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    I believe ME is autoimmune as well. The massive rise across the northern hemisphere in autoimmune disease is still a puzzle to scientists - and as the research is so fragmented is likely to remain so.
    I have a child with type 1 diabetes which is autoimmune and one with severe gut problems and gluten intolerence. My guess is that if she ever gets a biopsy she will be dx with some form of celiac which is autoimmune.
    If doctors took proper family histories instead of only asking very very limited tick box questions they might learn something.
    I know other families with ME and other autoimmune diseases in them.

    I also think female hormones are at play in a lot of this. The pituitary runs the whole show and we have a lot of complicated and finly balanced hormones ensuring growth, fertility and other stuff. They are all interconected. (Another massive mistake in modern medicine is the horribly piece meal approach. Multidisciplinary teams have vanished since the 1980s in the UK)

    Anyway, that my 2d worth. (anyone else remember when 2p was 2d?)
    justy likes this.
  16. Persimmon

    Persimmon Senior Member

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    Alex, that sounds very like Dr Chia's theory. In fact, your example (infection at 10; trigger sets off illness at 20) corresponds closely to what Dr Chia thinks happened to his son.

    I have one question about this hypothesis: is it easily reconciled with the apparent success of Rituximab?
  17. Mattman1

    Mattman1

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    Triggers are what I wonder about often as we'll; can this one disease have multiple triggers. Looking at this forum, one would have to conclude it to be likely-- the fire can be set in multiple ways. I like what Chia said concerning how he tries to get a detailed history of a patient in the events leading up to becoming sick-- if we can't really find bio markers now, than it seems that finding all possible causes of ones illness is one of the most practical things we are left with.
  18. alex3619

    alex3619 Senior Member

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    Hi Persimmon, what I am saying is not based directly on Chia except that it is Chia who supplied a lot of the data on tissue infection by enterviruses.

    The issue about what happens at one point and then later is based on my two hit hypothesis. I have been discussing that for many years, since long before I joined Phoenix Rising. It was very unpopular back then.

    However, you are right in pointing out my current hypothesis is very similar to Chia's.

    What changed my mind to make me view this as a leading hypothesis:

    1. The Rituximab trials. Nearly all the candidate pathogens infect B cells. They can leave their latent state and lyse the B cells when they pass through inflammed tissue. Enteroviruses do this, though most of our other pathogens do too.

    2. Infected B cells with a latent virus are likely to have disturbed chemistry, and a short lifespan. We now have three occasions where we have seen research that shows a lack of mature B cells in us, though absolute numbers are usually OK.

    3. Enteroviruses infect muscle. We have litte idea of what they are doing, but it cannot be nothing. A buildup of any substance in a cell will cause a decline in that cell's function - it doesn't matter if its beta amyloid, prions or virus particles. The vast majority of blood vessels in the body are wrapped in a layer of muscle, even if its very thin. That partially mediates our blood vessel response - its the muscles that largely determine vasodilation or vasoconstriction. What happens if an enterovirus is infecting most of those muscles? Could this explain OI? POTS versus NMH are about how the brain and heart deal with OI, but the OI itself could easily be from an enterovirus.

    4. The primacy of the gut integrity: autoimmune, autoinflammatory and cytokine issues can in part be linked to suspected gut dysfunction. A marker for this is elevated serum LPS. The gut itself might be asymptomatic, but if LPS is in the blood then the entire immune system is primed to do something. I am trying to figure out what that something is. When you look at long term chronic infections of the gut a leading candidate, with other properties we suspect are important in ME, is the family of enteroviruses.

    5. Enteroviruses, like most of our candidate pathogens including herpes viruses, have a latent state. We are used to thinking of that as the virus being quiet. That is not the case, at least for enteroviruses. These viruses have three virus lifecycles. The first is the classic infect-replicate-lyse-infect cycle. The other two involve genetic modification of the virus. These virus particles can replicate, but slowly. That means they can produce low levels of viral proteins and nucleic acids. This is not ideal, and may result in constant low level immune activation - just as we suspect in HERVs. When did I discover these additional lifecycles? The day before Christmas last December.

    6. One of the consequences I suspect, but cannot prove, is that elevated serum LPS will cause substantial migration of a cell type called gamma delta T cells. If these become depleted in the gut, there are three consequences. The first is reduced immune surveillance, leading to increased infection of the gut. The second is decreased suppression of autoimmune and autoinflammatory processes in the gut, leading to increased inflammation and risk of autoimmune consequences. The third is reduced healing of the gut wall. Gamma delta T cells do a lot.

    I may say more later, I only just woke up and want my first coffee for the day.

    Bye, Alex
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  19. redo

    redo Senior Member

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    Hi Alex. Thanks for your feedback.

    If it's true that the prevalence of ME in women and men are equal (or somewhat equal) before puberty kicks in, then that would increase the likelihood for a thought 'ME linchpin virus' being exogenous. Do you know of any such studies on prepubertal prevalence?

    The hypothesis of methylation issues being involved (which I support) fits very well with the endogenous retrovirus hypothesis. ERVs can be silenced by DNA methylation (there are many articles on pubmed addressing those mechanisms)

    That would be interesting to read. I also think that LPS plays a role. I wont go into that in this post, yet I think it's a piece of the puzzle. When you write that it triggers ME, are you putting it alongside other triggers (EBV, giardia, the flu)? I don't think of the LPS issues as a «hit and run» thing. I rather think of it as something which contributes to making the patient symptomatic, and stays with the patient throughout the course of the illness.

    The idea behind the ERV hypothesis is that each patients immune system might react differently to the same infection, and that might cause a patient to get for example ALS instead of MS. There are also many different ERVs which are not yet known if they cause illness.
  20. redo

    redo Senior Member

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    Thank you for your input, MeSci!

    I am tempted to add a 5th piece which must fit to any theory of ME
    5) Syndromes such as ME, FMS and MS have become more prevalent in the last 100 years, and a theory of ME must seek to explain why.

    If anyone have either any more things to add to the premise list, then please do weigh in. And if anyone knows of mechanisms which can explain the increasing prevalence, and still fit with the other four on the list, then please do weigh in.

    If I'd read any studies showing quite clearly that the increase can't be merely due to people getting the diagnose more often (after all not all of the diagnoses existed a hundred years ago), then I'd be happy to add the number 5 to the list!

    I think the reason for the assumed increasing prevalence is gut issues. We know all to well what feeding the bacteria in the mouth with the 'wrong food' does (read: cavities). In the gut there are 10 times more cells than in the whole human body, why wouldn't feeding them with a 21st century diet with among other things lots of sugar, lead to somewhat similar consequences as we see in the mouth...

    I think ME doesn't erupt without issues like that (that doesn't mean in any way whatsoever that one has to feel bloated etc).

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