So I've really been researching hard into what are the feedback loops that perpetuate chronic illness. I think I'm starting to piece this thing together.
Basically, from what I've discovered, neuro-inflammation is at the heart of almost every chronic disease out there. And when I say "inflammation", i'm not talking about
the classic rheumatologists version of "autoimmunity" where in a b-cell creates an antibody which attacks the body.
I'm talking about
neuro-inflammation perpetuated by micro-glia. I must have read 20 pretty heavy scientific papers on this, from diseases ranging from alzheimers to major depressive disorder to chronic lyme to CFS. It's always the same story:
The microglia in the brain get angered by some sort of stressor. This could be a pathogen (lyme) which triggers a PAMP (Pathogen-Associated Molecular Pattern), or a toxin, or psychological stress or even alcohol abuse, which triggers a DAMP (Danger-Associated Molecular Pattern). As an aside, this ties into the P2X4 purinergic pathway that Neil Nathan/Navieaux talk about
w/ the Cell Danger Response, but that is only one of the related pathways.
When this happens, the micro-glia (and toll like receptors that they interact with) get upset. Theyre the immune system of the CNS. They begin to release cytokines, which makes the astrocytes fire ion-channels which fire glutamate and causes brain changes. This is called hyper excitability. This is the biggest piece of the puzzle. Once the glial cells shift from M2 (anti-inflammatory) to M1 (inflammatory), neuroinflammation becomes chronic.
This leads to autonomic stress. Autonomic stress directly impacts the gut microflora through the vagus nerve. There is cross-talk between the gut and the brain. The brain talks to the gut through the vagus nerve, and the gut talks to the brain through the various neuro-transmitters.
As autonomic stress picks up, the microflora starts to change. The vagus nerve cannot stimulate the gut to rest and digest. This change in gut metabolism leads to the creation of various gram-negative bacteria, such as e. coli and streptoccacus, which release lipopolysaccarides. These LPS are endotoxins to the brain, and directly stimulate glial cells. And around and around the loop goes. This trigger of the glial cells due to the release of LPS is one of the biggest drivers of neuro-inflammation.
This is why we all keep coming back to the chicken and egg problem. Does gut dysfunction cause the neuro-inflammation, or vica versa? The answer is that these things happen co-incidentally. It can start in the gut, or the brain, but the because of the cross-talk, the patterns become ingrained and strengthen each other.
The take-away is that once homeostasis breaks down, it's very hard to correct. It takes a multi-systems approach.
You need to 1.) clearly remove any offending pathogens, but this may not be enough in itself for people who have been sick for a long time 2.) fix the gut and any sibo that is present 3.) stimulate the vagus nerve and fix the autonomic nervous system 4.) YOU NEED TO CALM TO GLIAL CELLS DOWN. This may be a big reason why LDN helps many people.
I can post papers on gut-brain axis, on glial cell activation, on signalling pathways in the brain, etc, later. There's too much to post in one spot.
But people may find this article interesting on some suggestions for ways to calm the glial cells down.
https://www.healthrising.org/blog/2017/09/15/glial-cell-inhibitors-next-sleep-drugs-fibromyalgia-chronic-fatigue-syndrome-mecfs/We also need new approaches to autonomic nervous system reset. DNRS is not enough. Has anyone tried vagus nerve stimulation?
Post Edited (dcd2103) : 3/10/2021 7:02:44 AM (GMT-7)