It's totally an oddball and crazy thing that propped into my head again today but here is what I was thinking about
geometry:
It's nothing new or shocking, just an observation, but thinking back to all the stuff on nano particle issues where these guys have been trying to sneak small things across the mucus barrier for a few years now in order to increase absorption of meds etc. The mucus barrier is quite the structure and prevents a lot from getting through. So it's been driving them nuts how to accomplish this. So they try and encapsulate meds in super small particles (smaller than bacteria) to pass right through. Which they still have difficulty doing. Bacteria on the other hand are quite large. From all this we learned one very important thing; geometric design of the tight first layer of mucus. This comes from the direct imaging they did.
What was realized is that the tight layer can be visualized in sort of a 3D diamond structure. So like this if it works:
Figure 1
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Figure 2
Picture the above diamond shape but with random straight lines protruding here and there inside and outside.
But 3d. Nature engineered mucus this way because of it's efficiency in trapping all shapes. So if you put a rod shape or circle shape bacteria inside this basic 3D diamond structure (Figure 1) it can enter from one direction - through the wide
opening, but barring any movement in another direction it becomes trapped.
Now, the bacteria could move through this structure somewhat easily through all the wide sections in the 3D diamond mesh or web. Especially rod shaped bacteria on end - they could pass straight through. So what nature did was create these little random straight fibers or filaments that project outward in odd directions (figure 2). These "random" fibers condense some of the
openings and significantly reduce the pore size down to something smaller than typical bacteria. So now the bacteria when they enter this tight mucus can get in to a certain point, even on end for rod shapes but eventually "bump" into these fibers. As soon as they do the diamond shape "locks" them in place. And the straight fibers prevent them from literally being able to turn around. They can't wiggle their way out or through. It traps them, immobilizes them, and eventually sheds and gets rid of them.
It's such an awesome design that is meant to trap things, in fact there's no better way to accomplish this - It's the geometry more than anything that prevents bacteria and other foreign objects from getting through.
In the small intestine they say there's only one layer - and sometimes none - so Patchy. And the paper you most recently posted said this is perhaps because of the speed in which stuff flows through. Also in the distal colon, it's thickest (or tight and thick), again due to speed and the length of time things sit there - but I think it's also because that's the dumping ground for all other access points - the mucus elevator eventually empties everything there, from the epithelial barriers in the lungs, eyes, nose etc etc through the lymph system.
Anyway - back to the 3D Shape - The paper talks about
repeating structures of Threonine, Proline, and Serine - this makes a lot of sense because these would form the basic super tight 3D Diamond structure when joined or bound/linked together And this is described in your paper you posted... More importantly I don't think they would be very soluble until they and the O-glycans attaching them and making the 3d Diamond web structure were acted upon by an enzyme or oxygen, lipids (fatty acids) etc. And this would come from dietary intake and the bacteria that feed off them themselves. So the 3d Diamond mesh loosens up and expands as it get's closer to gut lumen and so on - and this process eventually expels the bacteria for elimination. So it might be the luminal side that has one of the biggest effects on the expansion of the geometry or mucus. The wide side of the 3D diamond shapes get larger and larger the closer they get to more of the acids, enzymes and so on in the lumen. The more of this stuff present in the diet (and ultimately the lumen) the faster it expands.
We learned the tight mucus layer replaces or regenerates roughly every hour. Which is quite a lot and is probably because of the need to expel all the crap. Otherwise the filter media (mucus) would get totally and completely clogged up just like a filter. And nothing would get through. More so water also needs to be absorbed by the body and this happens in the colon as well. And even more so water would play a role in the expansion by a reaction with the extra oxygen molecule and the o-glycans. H2O. The more water/oxygen present the faster it can degrade - or something like that. Oxygen might be a problem from this standpoint is the main point here.
Constipation could be some sort of super tightening problem. (totally guessing)
Anyway,
The random vertical fibers protruding outwards (that trap the bacteria and foreign objects) inside and outside of the diamond mesh are made from sugar molecules (o-glycans) topped off with a cysteine molecule. This is described in exact detail in your paper. Cysteine is not very water soluble. It takes a lot of water. I believe serine is what primarily breaks this up. So again I believe the bacteria that have serine protease enzymes would be good at this. Not being easily water soluble is the important point - It gives structure and helps "lock" bacteria in place so they can be flushed out as the mucus eventually expands.
I think here's a picture painted here in this paper you posted that you can easily visualize how and and why the initial tight mucus layer is formed, what its made out of, why it forms the shape it does (specific chemical properties of the three main repeating proteins), how and why it expands (enzymes, oxygen, serine) and how if this is even just slightly altered the 3d diamond structure would change and
open up and the straight filaments (with Cystine) would
open up as well - allowing bacteria to not only get through but actively participate in making it almost impossible for the body to keep up with replacing it. Draining the bodies reserves of these specific amino acids.
So your thoughts on this being the thing to fix, from a geometry perspective makes a whole heck of a lot of sense to me. Or as that paper you posted states (the initial event). From here everything goes wonky.
I really, really, really think your totally onto something here about
needing to find a way to fix this issue - or make up for it to give the body what it needs due to some sort of genetic effect in the process... in all cases I think it comes back to wonky mucus geometry and perhaps a miss-shaped mucus barrier. Fixing the geometry fixes the problem.
I sorta typed this pretty fast so hopefully it makes a bit of sense. I have papers on the geometry of the mucus barrier somewhere form the nanoparticle stuff.
Anyway Cysteine may be very important as well to allow the body to make the filaments and design the tight traps for bacteria.
I'm off to think.
PS - I picked up some Proline today - and thought I bought Threonine but turns out it was Taurine... so I have to go back tomorrow. I took 1 mg of Ploine tonight anyway. Maybe I'll take another mg before bed. I'm going to try this as well. I got nothing to loose at this point and the whole thing just makes sooooo much sense.
Awesome work! Keep digging.
Post Edited (Canada Mark) : 9/24/2013 6:25:58 PM (GMT-6)