brucen36 said...
I've read the paper outlining the theory. It's interesting. I'm not saying it's wrong, but if you read carefully, it is indeed very speculative. I hope it's right as that would at least focus therapeutic development to the right source.
He has new peer reviewed study coming out shortly. I think we should withhold our judgments until we see his update.
brucen36 said...
However, regarding it not being full invasion in mild UC, according to the theory, at least some bacteria is gaining access through the tight junctions to the basement membrane. If the immune system is not able to fully respond, then what happens to these bacteria? They should persist and replicate within that compromised environment. Their numbers will continue to grow since nothing is inhibiting them (due to immune suppression drugs), until they can indeed begin a full invasion and cause sepsis. But this does not happen. So I'm not sure I fully buy this argument.
UC is not transmural like Crohn's, so you are not going to see auto-infections as often, unless there are very deep ulcerations to the point of perforation. Biologics and immune suppression don't fully deactivate the immune system, they simply inhibit its migration into the bowel. The science behind this is consistent. I invite you to read more about
the pathophysiology of UC and how the gut wall functions. Tight junction disruption is not analagous to perforation/sepsis, but it's enough to sensitize the immune system to colon bacteria and begin attacking.
brucen36 said...
Regarding the autoimmunity, you kind of contradicted yourself. You said the bacteria are uniform through the colon and so autoimmunity should be equal along the entire colon from the beginning. But then you follow it up with the rectum has the highest concentration of bacteria. If it is auto-immune, then rectal only disease is possible for pretty much the same reason you outlined for H2O2, the highest concentration of bacteria are in the rectum and so it begins there first. As the overall load of bacteria grows due to various stressors, the concentration passes a certain threshold so it spread to higher parts of the colon, which formerly were below the threshold. Again, not saying auto-immune theory is wrong or right either.
I'm talking about
immune system sensitization. Auto-immune means that the immune system is attacking the body's own cells or it's attacking something inherent to the body like gut bacteria. The gut of infants is colonized very rapidly and childhood exposure to bacteria informs the developing immune system. The prevailing UC theory is that the body is either attacking its own colon cells or it has "forgotten" to not attack native gut flora.
What I said in my last post, which is not contradictory, is that if the body has developed an immunity to its own gut bacteria OR the colon wall, then why is only the last 12 inches of colon affected? The concentration of bacteria is irrelevant to auto-immune theory. If the immune system is attacking rectal bacteria then it should also be attacking ascending colon bacteria. Similarly, if it's an attack on the colon wall itself, then why just the rectum, when colonocytes are in the entire colon?
The reductive theory of disease explains this. The rectum has the highest concentration of oxidative stress because it is where waste is the most concentrated and bacterial counts are highest. So cell turnover is highest. It's not because (as you claim) that bacterial load is highest so more bacteria are leaking into the body. That is not how the pathophysiology of UC works. The immune system doesn't *cause* leaky gut, it *responds* to it.
What you are saying about
spread of UC according to bacterial counts pouring over into higher areas is incorrect. Even conventional UC theory would not agree with you. There is not an out of control bacterial problem causing auto-infection that spreads. UC due to infection is uncommon. Most UC patients have normal gut flora species, the ratios are just way off.
brucen36 said...
Food doesn't cause sepsis, again because of a matter of concentration. When food gets past the barrier, it doesn't replicate, whereas bacteria that get past can replicate, and so only they should cause sepsis.
The immune system is still active even during so-called immune suppression. Neutrophils don't disappear from the body, neither do macrophages. Their access to the mucosa is hindered by drugs. UC is a mucosal disease, it is not transmural. In UC, ulcers develop which fester due to colon bacteria. The ulcers have to get deep before sepsis occurs. The gut immune system is incredibly complex and leaky gut does not mean bacteria automatically get to enter the rest of the body and start replicating.
I understand your reasoning but it's too simple-pointed. There is more going on than 2 or 3 factors.