Team identifies possible bacterial drivers of inflammatory bowel diseases

Thanks OM.

Hmmm, the mice used in the study Mark originally posted for this thread were the mice that were prone to developing chronic inflammation after DSS cessation (the C57Bl/6 type). That's good to know. I'll go through the study again and see if it reads any differently now that we're aware the mice are also genetically susceptible to not recovering after DSS.

As far as remission goes: I still think this study supports the idea that doing something to treat the bacteria causing pro-inflammatory responses and the repairing the mucus can induce remission. If the root problem is genetic susceptibility that causes the break in the mucus barrier not to fix itself, then maybe fixing the barrier and treating the bacteria that are causing the symptoms can be enough to effectively treat the disease and possibly induce a robust, lengthy remission. Those genetically susceptible individuals may always be at risk of the barrier randomly breaking again.

I still think that those who of us who got UC after antibiotics may have experienced some sort of weakening in the mucus barrier and then dysbiosis lead to a pro-inflammatory microbial community that is not easily resolved. If the mucus is permeable for whatever reason which causes too much pro-inflammatory bacteria to invade the mucosa, it seems like it could cause a cycle of inflammation that keeps destroying the mucus barrier and does nothing to resolve the underlying dysbiosis causing the immune reaction in the first place.

So in essence, with my very shallow knowledge of this condition so far, I'm suggesting that in some people, genes may be the primary factor, in others the dysbiosis is the primary factor. Both seem to require a break in the mucus barrier to induce (the bacteria placed in healthy, colitis free C57Bl/6 type mice did not induce colitis) and both groups may have different genes and different bacterial makeups which means treatment will often be individual.

Even if I am totally wrong, I still think treating the pro-inflammatory bacteria will yield good results as far as treatment goes.

Marauder93 said...
@ Tunnel - Just so you know, C57BL/6 mice are the most common and standard type of lab mouse, they are nothing special. They CAN be induced with chronic DSS-induced colitis, but it takes a special protocol with many cycles of DSS. If you treat them with DSS for 5 days only, they will recover from it.

Oh. My bad. Thanks for clarifying though. I'm just starting to read into all of this stuff.

Reading through the paper a second time, interesting point I found.

Page 5 of the paper says:

"The bacteria that we identified as highly coated in SPFdys mice are known to colonize normally sterile mucosal environments, such as the inner mucus layer and intestinal crypts."

Even though in healthy conditions, neither the IgA+ nor the IgA- communities induced colitis, once DSS was added (something induced a break in the mucus), the IgA+ communities created severe disease and invaded the mucosa, while the DSS mice with IgA- communities were pretty much okay.

Maybe all it takes is one opportunity for bacteria and once they invade the mucus, it is difficult to stop.

Whose site dedicated to the mucus barrier is that? It's really informative.

Also, I have a question about something in the IgA coating study...

So we are not sure exactly how the immune system identifies pathogens and differentiates them from commensal bacteria with similar elements. But they suspect their activities can mark them for destruction as if they were a pathogen, i.e. being somewhere they are not supposed to be activates the immune system.

The IgA+ bacteria were all known to invade the mucosa when initiated into germ free mice, the IgA- bacteria did not penetrate the mucus.

The IgA+ bacteria also induced an IgA response to those same bacteria while they did not for the IgA- bacteria.

But even with these steps, and even with the penetration of the mucus... colitis was not induced until they added DSS.

Did I read that right? They observed that the bacteria penetrated the mucus, but nothing happened when they were introduced into the mice in healthy conditions... so is it simply the penetration of the bacteria doesn't cause the immune dysfunction?

I love this study but it does raise so many questions that I just want answered NOW. Haha. :)