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New E. coli study

Why wait for endless promises. Kefir and kombucha will help this very day! :)
 
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But then I don't understand if you use ustekinumab to block TH17 proliferation how come AIEC does not spread more? So why immune suppression does not make the disease worse?
 
One possibility is that the bacteria don't really invade tissues that much, so not having an immune response to it might not actually be a problem aside from possibly allowing the bacteria to become more widespread in the gut. Most likely the vast majority of the damage is caused not by the bacteria but by the immune response.
 
Anti-inflammatories are often used during infection to prevent tissue damage from an inflammatory cascade.

The only way to explain the deep transmural tissue inflammation in crohn's is that there is direct contact between tissue macrophages in the lamina propria and pathogens. Only macrophages that release TNF-a and dendritic cells that present antigen can cause the adaptive immune system to mount such a deep tissue response.

Inflammation compromises the intestinal wall, resulting in AIEC and other bacteria gaining easy entry into deeper tissue. There they will encounter lamina propria macrophages. These macrophages are everywhere in the intestine, there are more in the intestine than anywhere else in the body. These macrophages are unable to kill AIEC, end up releasing TNF-a, antigen presenting cells set off the adaptive response and you get a chronic loop of bacteria setting off inflammation and exploiting the tissue damaged caused by the inflammation.

The only way a bacteria can become a chronic infection is if it is able to thrive in an inflammatory environment. And yes, there is some irony there that the immune system which does its best to curtail pathogens entering tissue, can also damage that same tissue which allows that bacteria to enter tissue.

The immune system in crohn's disease patients can kill and control AIEC and pathogenic E Coli to a large degree, but these bacteria are able to evade much of the mechanics the immune system uses, especially those of the innate immune system (Xenophagy to name one), which means they become chronic infections, resulting in a chronic disease involving inflammation.

Crohn's is really an immunodeficiency of macrophages, combined with a chronic infection, likely involving E Coli in many patients, and possibly other pathogens in others.
 
The AIEC mentioned in the study are of course not "gut bacteria", they are purely pathogenic and have invaded the intestine, you'd think the fact AIEC has the word "invasive" in its name would be enough of a clue for them to properly describe these bacteria. AIEC are not supposed to reside in the gut in any shape or form.

When someone develops intestinal TB, and develops inflammation and granuloma in the small intestine like crohn's, we don't call these mycobacteria "gut bacteria" either, we call them pathogenic threatening the life of the patient.

It has been slow going before GI and others recognize that crohn's is simply a chronic infection where bacteria chronically activate lamina propria macrophages. This results in tissue damage. Anti-inflammatories can prevent the tissue damage to a certain degree, but it of course doesn't solve the infection, the disease and inflammation become chronic. The studies are fully behind this theory now, even though the language used in articles is still often missing the mark.
 
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You can ask the question how AIEC and other bacteria initially gain entry to begin with.

There is a very small part of the "healthy" population running around with AIEC too. It is a very small single digit number compared to people with crohn's disease where we can find AIEC in 60%-70% of patients, and the forms of AIEC you see in those "healthy" individuals tend to be less invasive.

Still, even though some of these people probably suffer from some intestinal issues because of it, they can not be classified as having crohn's. They likely run a high risk of developing crohn's, but they don't have the disease.

So you can ask the question how AIEC gained entry to tissue in crohn's disease patients.

It's not like we are born with crohn's, it happened rather acutely. It didn't happen over years or months. We went from having no intestinal issues to having a serious disease in a matter of weeks or days.

I'm not sure if answering this question is helpful for us, but the initial cause is likely something that compromised the intestinal barrier. Foodborne infections like E coli, salmonella, campylobacter can all do this.

The little data we have about very early crohn's disease diagnosis, where you can see the early events unfold, shows involvement of peyer's patches. Many bacteria gain entry in the small intestine through peyer's patches, including foodborne bacteria and AIEC.
 
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