Bacteria Are Smart Little Ba$tards
The whole lymphocyte thing made me look at the chicken and egg or breakdown/dysbiosis from a whole new viewpoint. Just can't type it out.. I'm sick and done tonight. This flare is killing me.
Maybe I'll try a super short version, but I gotta rest here.
I'd look at the "full breakdown" of the mucus layer more like the "defining event" rather than "the initial event" - The full or complete breakdown in an area leading to bacteria "penetration" - which then leads to bleeding and ulcers. So more so the defining event of UC. Guess it's all just wording though. In any case here's a thought.
As per that paper you like on emulsifiers shows that a simple test showing feces coated with lymphocytes is enough to diagnose UC with something like 85%+ accuracy - and to differentiate it from Crohn's. That's pretty remarkable.
Lymphocytes obviously play a very big role. We've heard this as well from the immune overdrive/autoimmune type stuff forever...
Here's where I started thinking different about
things though:
In DDS colitis - breakdown of the mucus barrier was the initial event that allowed bacteria to pass through, but the actual "bacteria penetration" resulted in the onset of colitis - not just the weakening or loosening of the mucus barrier. Unless i have misread that paper again, which I have gone though a few times now.
However this is a completely chemically induced version or model. This we cannot forget or overlook.
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Bacteria - 3.5+ billion years of smarts and I really doubt that any bacteria is not fully and completely opportunistic (commensal or otherwise). And they have been trying to get at us for as long as we have existed. SO they're super smart and crafty to say the least. We've co-evolved though as we use their byproducts as vitamins and energy and they feed on our mucus... but still. Bacteria should not be in contact with our colon cells or have easy access to our bodies in any way. They live on our surfaces... Or so I am lead to believe. And they really need to stay there on those surface, not inside us.
We have a protective barrier - Mucus... and a protective friend - bacteriaphages... and an immune system to respond to situations. These look to be our three primary defense mechanisms. All involve the mucus.
Turns out lymphoctes secrete proteases... in part to break down mucus quickly and help shed away bacteria. (I'm like 99% sure on this but have to do some re-reading)
Human genome project and others show very, very high concentrations of bacteriapaghes in people with UC/IBD - which means either their environment is stressed or their trying to infect and kill off a type of bacteria they don't like or that is threatening their normal "environment" - the mucus...
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So here's the bottom lime on my new line of thinking:
Stress (hormones)
Smoking
Food
etc etc....
All effect the bacteria make-up/diversity in our body.
Certain chemical additives seem like they effect our mucus and maybe even our bacteria diversity as well ( but I'd say indirectly on the bacteria diversity)
Hormones again and antibiotics seem to directly effect our bacterial diversity - both in positive and negative ways.
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Bacteria are smart little ba$tards... and opportunistic.
I think we've just been confused, by all the information and all the crazy immune responses and all the crazy pathways and well - we've just had the curtains pulled over on us..
I now think the most important paper you've posted is this:
medicalxpress.com/news/2013-09-collaborative-effects-multiple-bacterial-strains.html - BUT for a different reason.
In fact for the complete opposite reason, that I never thought about
till I read that article this morning and thought about
it all day long. "These strains collectively secrete a host of signaling molecules" and ""None of the organisms alone were nearly as potent as when they were in consortium" In the articles case it was to our positive advantage.
BUT the same will undoubtedly hold true for negative advantage.
I now think just a slight alteration in bacteria, (probably not even enough to really measure or even classify as "dysbiosis") is enough to be the primary trigger - and due to opportunity (smoking, stress, diet, antibitoics etc) gave just the right foothold or slight imbalance for a small group or gang of them to gain a foothold to release enough host signalling molecules to
"TRICK" our immune system into helping them get through the door (the mucus)... They signal and use our lymphocytes against us and we mistake this as fully from the immune reaction to them. Or an autoimmune reaction. When in fact it's these lymphocytes and the immune reaction that are actually helping them.
Remember bacteria are also at war with one another - trying to out compete each other for food resources and such. A small gang of a few basic strains with a common goal to break through would benefit highly by tricking our immune system into an inflammatory response to flush away the other bacteria they don't like.. or are competing for the same resources. These guys or the "gang" would just have the advantage in numbers and perhaps
location (further into the mucus) and flushing the good guys out that are on the outer layer would help their cause tremendously.
And more so the whole thing would start with just a little patch and in the area with the most and worst types of bacteria - and depending on how successful they were with their attack, would grow from there not only in length (throughout the colon etc) but in depth (into the inner mucus layer and eventually into their target - Us) and in numbers... Leading to a full state of measurable dysbiosis.
Fecal Transplants - may help some but I'd say more so from pure luck, but in some cases may make the situation worse by accidentally providing re-enforcement's to some gang or patch of commensals.
I'd really, really, really like to see what the LONG TERM results would be on fecal transplants for people that did this while on biologics and in full "clinical remission".
After all - we know that even when you reach full and clinical remission on biologics, and then stop, the disease usually comes back with vengeance after time. I now think biologics are simply stopping or hindering the "gang"... But not getting rid of them but simply by reducing the amount of lymphocytes or reducing tnf-a etc (their weapons of choice) that they can call on or signal to help them. SO they sit and wait again for the right opportunity... and wham...
PS - I'm not really suggesting lymphocytes are the primary or only mode or Modus operandi but trying to illuminate a common theme or path - shed some light through the curtains. Other gangs could easily "trick" our bodies into secreting excessive amounts of tnf-a as "their" weapon of choice when ganged up and opportunity is present. Such as the case with AIEC - Adherent Invasive E Coli. etc etc etc... and there's many others... they all have their own weapons and would become far more powerful in a "gang mentality" state. So many different ways for the disease to take hold. Again, their primary cause is to break down and get through the mucus. What better way to do this than engage us and have us do it for them?
That's my crack at it tonight... I guess it's the long version after all.
I'd go to bed but I can't get off the darn toilet...
And still, regardless if this is a nutty or whacky idea there's just all the more reason to fix the mucus... As Mike says. It looks to be the primary ummm starting point... it needs to be fully operational to do it's job in providing a barrier, providing food (bacteria) or more correctly a reproductive method to our bacteriaphage friends and an attachment point for them to adhere to (the mucus web) and providing food for multiple bacteria types in our colon and not allowing a gang of a few to grow, recruit new members and to overpower/manipulate the entire system.
Post Edited (Canada Mark) : 9/28/2013 1:26:46 AM (GMT-6)