Regarding the serial FMT study: Really glad they are looking at multiple FMTs and how it affects gene expression. I have yet to read it more fully as that doc won't
open on my computer, it only
opens on my cell phone. Just woke up too.
I think I've read pediatric/early onset IBD tends to be more aggressive and more tied to faulty genetics, which could be a reason for the volatility.
Also I forgot to mention in my other post that DIY FMT prep and probably FMT done in the hospital exposes the stool to a lot of air killing many of the anaerobes, which could potentially be beneficial. Additionally, I feel it's flawed to only examine the bacteria present in the fecal matter, what bacteria stuck to the mucosa? I'd imagine the patient's stool would end up looking very similar to donor stool considering it was implanted into the colon, so i'm not sure how helpful it is to measure patient stool bacterial comps and conclude that the microbiota took hold.
It says that they did get into remission, but relapsed 11 weeks later. That's unfortunate, but not totally unsurprising. Don't know what to make of this really, could be anything, including that FMT just didn't work as a long term solution for these kids.
Regarding usefulness of FMT in light of recent discussion
If UC is in fact bacterial breach of the mucus layer and this is causing the run away immune response (and this is not a secondary effect) then it would make sense to think that FMT would only make things worse. FMT can make things worse for some people with UC, but many report either no effect or a positive one.
My thinking is that despite FMT introducing more bacteria into the mix is that the wider diversity and beneficial strains are immuno-regulatory to help calm down runaway immune responses potentially as well as thicken the mucus barrier itself. Metabolites may have effect as well but I don't know much about
that. Generally I think the wider bacterial diversity introducing immuno-modulating effects as well as strengthening the mucus barrier are the two critical components of FMT But maybe timing is important, if the mucus barrier is too messed up, then maybe business as usual occurs. Would also need to research more how microbes and their genes and metabolites effect the strength of the mucus barrier.
FMT possibly fails on its own because many transplants are prepped with lots of exposure to air and I can imagine with the gut being mostly anaerobes that that could have a big effect. Inflammation present in the gut kills off lots of commensals except for those that are resistant to inflammation (possibly a reason why the inflammatory response is chronic, lots of bacteria won't die from the inflammatory response medicalxpress.com/news/2015-01-harmony-friendly-gut-bacteria.html
) which might keep the immune response going. Disease progresses because the mucus layer continually gets beat down by inflammation letting more inflammatory-resistant commensals through/more biofilms forming/etc? Perhaps biofilm explanation is not even necessary, commensals are already pretty inflammation resistant. Then again, if biofilms do play a factor, they may potentially get in the way of the mucus barrier regenerating properly.
Admittedly, my view on UC is slanted to explain my own case and cases similar to mine. UC symptoms correlating with antibiotic use. No family history of autoimmunity (though maybe its just starting to show up in my family now through me? *shrugs*). However, in absence of any host-genetic defect with the mucus barrier or immune system, I think just generations of family living in industrialized societies with reduced bacterial diversity and lots of antibiotic use could make this thinking broadly applicable, not just to cases tied closely to antibiotic use.
So my thinking is that bacteria/FMT can be effective at dampening the immune response and creating a stronger mucus barrier. But perhaps simply infusing bacteria themselves is not helpful. Fewer anaerobes are going in, maybe many get killed off due to inflammation...doing transplants while also working to restore the mucus barrier and calming down inflammation. Even if biofilms are an effect of UC rather than a cause, I could see that potentially getting in the way of restoring the immune system and calming down the inflammatory response. Might prevent FMT bacteria from taking hold as well.
Post Edited (Tunnelvisionary) : 4/9/2015 11:15:43 AM (GMT-6)