What are all the theories of what causes ME CFS?


Senior Member
You might find this interesting if you haven’t seen it: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222156/
It is about how poliovirus requires bacteria
Yes, I think I have seen similar papers where gut bacteria and viruses may promote each other.

Dr Markov's theory is that neither the bacteria or the viruses found in ME/CFS are directly causing this disease, but rather it is the toxins bacteria make that are responsible. Bacterial toxins are often lethal to humans in doses of around 1 or 2 μg, so these are certainly pernicious toxins. And if they were leaking into the bloodstream in sublethal doses, they could cause many ill effects.

Some ME/CFS researchers like Micheal Maes have proposed that ME/CFS could be caused by bacterial toxins leaking into the bloodstream from a dysbiosis intestines combined with a leaky gut (intestinal hyperpermeability). So this idea of bacterial toxins causing ME/CFS is not new. But the novel idea in Dr Markov theory is that the dysbiosis and leak are actually in the kidneys, not the gut, where all other microbiome researchers are looking.

To corroborate his theory of bacterial toxins causing ME/CFS, Markov found that 81% of 818 ME/CFS patients have severe levels of bacterial toxins in the blood (toxemia), and 17% had moderate levels bya blood test performed at an independent lab in the Ukraine. To my knowledge, Dr Markov is the first researcher to actually test bacterial toxin levels in ME/CFS patients (there was a recent study looking at LPS levels in ME/CFS, but LPS is just one of many bacterial toxins).

Nevertheless, viruses are the usual trigger for ME/CFS, so if Dr Markov's theory is correct, then we would have to explain how a viral infection can cause bacterial toxins to suddenly start entering the blood. It may be that the virus infects the kidneys and causes the kidneys to leak, and then a pre-existing bacterial dysbiosis in the kidneys starts to become a problem. But that's pure speculation, and it's really anyone's guess.


Senior Member
Certainly, it is possible to persist without a sustained etiology. I already described one possibility, I think. That is, the chronic or acute over-sensitization of the vagus nerve leads to a glutamate-mediated destabilization of microglia. These microglia then release cytokines and glutamate which leads to a cascade of localized neuronal overactivity. Just looking at the microglia, there are many other options on how they can be destabilized, e.g. viral infection of the stem brain, macrophage/monocyte migration into the stem brain, cytokine transport into the stem brain. The glutamate metabolism itself also plays a role, e.g. too much glutamate provision from glutamine or from a dysregulated citric acid cycle, or a dysfunctional glutamate decarboxylase due to B6 deficiency.

Moreover, there are secondary inflammatory feedback loops that can stimulate the vagus nerve after NTS pathology onset. For example, NTS pathology can alter the gut microbiome, dermal microbiome, and this then causes inflammation or opportunistic pathogens to take over, which again stimulates the vagus nerve. Viral reactivation is another factor. NTS pathology can trigger viral reactivation while the viral pathology then enhances the NTS pathology via the vagus nerve and possibly by macrophages and cytokines as well.

All of these feedback loops would have to be identified and solved in parallel. Otherwise, you're just trying to keep a ship from sinking by plugging one hole of many.
Do you have an opinion or thought about the adenosine 2A receptor and it's involvement in the glutamate cycle? I just found this, but don't know much about it.

"The molecular bases of the adverse effects of A2A receptor stimulation are attributed to its modulation of neuronal glutamate release, potentiation of NMDA‐mediated effects, central inflammatory processes, glial reactivity, blood–brain barrier (BBB) permeability and infiltration of peripheral immune cells, which are associated with excitotoxicity and the pathogenesis of several brain diseases."