Why it's all in the gut 2.0, this is a sketch of the revised hypothesis
Please do comment this newest version of the hypothesis! Look for parts where I have overlooked something, or am wrong. Here goes:
I think the best way to push forward is to assemble a hypothesis and see if it's waterproof. No matter what lies behind ME, it must explain these three vital questions.
Three big questions in ME
Why can so different things such as EBV or vaccines, food poisoning or the flu trigger the disease?
How is the disease transmitted?
Why has it been increasing so much in prevalence in the Western world?
While I don't sit with all the answers yet, I will offer my explanation. The short story of theory is this:
There is a latent (yet to be identified) virus -> We get a temporary immune suppression ("trigger") -> the virus becomes active -> autoinflammation/autoimmunity becomes rampant -> ME symptoms arises
In this article I will do my best to explain the three big questions and the domino chain leading to the disease.
Why can so different things trigger ME? This is the most puzzling question. What dose EBV and a vaccine have in common? Or a giardia infection and a heavy flu? There are many more triggers as well, but the only common nominator I have found is that they temporary suppress the immune system. But that's that. A giardia and a vaccine aren't likely to cause the same type of immune suppression - unless. Unless there is a middle link, something they both can trigger, and something which than causes the symptoms. The prime suspect as to what can go undetected is RNA viruses.
How is it transmitted? If a RNA virus is to cause disease in the patient group, it must come from somewhere. And what could that be? Given how there are no prime suspects, I have come to the conclusion that to the question as to how it's transmitted, the answer
is really that it isn't transmitted. We're born with it. It's called endogenous RNA viruses and all humans are born with them. The reason why we all have them, but they don't do harm to humans is because the body has, throughout evolution, adapted, and learned to silence them. Of the endogenous RNA viruses, it might be a known one, or it is a yet to be identified one.
Why is it increasing so very much in prevalence in the Western world? It has increased in prevalence the last century. One could say, naaahh, that's just better diagnostics. But that's just a small piece of the story. We would surely know about it if 0.2-0.4% of all farmers (and people) lied in bed unable to tolerate sunlight, or unable to do daily tasks because of ME symptoms some hundred years ago. Better diagnostics doesn't explain it. Only a fraction of it. We have been seeing a steep increase in ME cases, and it's still growing in prevalence. And, it barely exists in the poorest countries in the world. Both in Africa and Asia there are large regions where you can't find ME sufferers. Why is that? One of the biggest differences is this reason; and it's also the same reason why it's been growing so much in prevalence in the west: What we put inside our 30 feet long intestinal tract.
There are 20 trillion cells in a human body. There are 200 trillion cells in the intestinal tract. Microbes which defend and define us.
Microbes which may be a reason for disease if they're the wrong ones.
Gut Bacteria Lend a Molecular Hand to Viruses, and aids in making viruses pathogenic. We know for certain that if we eat a western diet, we have much bigger chances for getting overgrowth of the wrong bacteria in the mouth, leading to cavities. But, what happens if we get overgrowth of the wrong bacteria further down? There are thousands and thousands more bacteria in the gut than the mouth. Can we do that without consequences?
Research is actually pointing towards a new gut flora being responsible for
giving RNA viruses the possibility to act out. What happens is that the new flora creates a hole in the immune system, which specifically paves way for RNA viruses. Now, we're in a situation where
endogenous RNA viruses, which the body has learned to quench throughout evolution, suddenly can become active. All it needs to activate is a trigger, and in some cases it doesn't even need that.
When the disease is triggered it has very close resemblance to how the
human immunodefiency virus acts the first months: First in ME there is a period with tender lymph nodes, general malaise and a flu like feeling which doesn't go away, and than it progresses on to the later stages month by month. Aside from the obvious, a big difference is that there is no latency period after it's first begun.
So to sum it up: We are looking at a latent endogenous RNA virus (which most, if not all humans have), it gets triggered by an immune suppressing event and the RNA virus than becomes active, the activation of the RNA virus leads to autoinflammation/autoimmunity which in turn leads to the ME symptoms.
Why can severe stress be a trigger for the disease? Among other things,
severe stress can change the gut flora for the worse, and thereby "sweep the rug" under the immune system for a period of time. That period of time might be enough for the endogenous RV to go from latent to active.
Why do we get PEM? The PEM, a very common symptom in ME, is mediated though methylation, glutathione and levels of autoinflammatory cytokines. The malaise and general worsening ME patients get after exercise is unique from ME, and the reason why these three things happen is either because an active RNA virus goes direcely at it, and makes it happen. Or it's because gut problems does not only lead to activating of RNA viruses, but it also leads to these kinds of problems. At the moment I am leading towards to first of those.
Why does our symptoms get worse from concentrating? An important thing which happens when we concentrate is that the body releases dopamine and nordadrenaline. With ME patients we have problems breaking down those catecholamines, which means they just keep building up and up and it's making us worse and worse. Taking a long time out from concentrating (hours or days) is what's needed to get back to square one again. The reason for these problems is
changes in the gut flora.
Why is it we get somewhat better with probiotics, antibiotics, antivirals and Rituximab? (they are such different things!)
With probiotics, what we do is alleviate the gut problems which have risen. What happens is that if we are able to change the gut flora for the better, the body is more able to handle the RNA virus, as very much of immune functioning lies in the gut. The reason why some of the patients get worse so quickly of sugar (within days) is because it temporary changes the gut flora allowing for the wrong bacteria to get a stronger hold.
With antibiotics, there's more a mixed bag of results. I've heard many stories of people getting worse from certain antibiotics, and what they do is suppress helpful bacteria in the gut, and allows the harmful bacteria to get a stronger hold. But, with other antibiotics, it could really go after the wrong bacteria, and be very effective at it, doing much
more good than harm. What happens than is that patient feels better, because the immune system functions better as a result of less of the wrong bacteria in the 200 trillion cell thing which is our gut content. And on top of that some antibiotics may act as anti inflammatory drugs regardless of the gut pathway of action.
With (normal) antivirals, many have immune modulating properties (such as also Montoya have proposed is the mechanism of action) and it alleviates symptoms. It might do it via going after a somewhat active co-virus, or directly by immune modulation.
With Rituximab and other immune modulators you go more directly at the immune dysfunction caused by the RNA virus. Autoantibodies or cytokines could very well be it. Wiping out the pathogenic ones, could work wonders on the patients.
Why do more women than men get ME? The endogenous RNA virus model would be a parallel to the
HERV-W model in MS. While much is uncertain about the gender bias in ME, it seems to affect more women than men. MS affects women two to three times more often than men. The reason for this is the same as what's behind the
HERV-W (RNA virus) hypothesis of MS. The genders respond differently, and much of the reason if the differences in the immune system.
Note. The links in the text are meant to be sources where one could read more about the general idea of a topic. More like a
interesting to read list, than actual sources for evidence.
My health is really poor at the time, so I haven't put in all the links which is supposed to be there. And this is a first draft of the revised endogenous (instead of exogenous) retrovirus theory. Let me know what you think? Are there any holes? Are there anything supporting the theory not mentioned? Is there something which crashes with the theory?