Also remember - from OM's 10,000 biopsy paper he posted on the other mucus thread: www.charite.de/arbmkl/themen/ubersicht/polensascha.pdf
5-asa's have antibacterial properties, just as antibiotics do, but they don't seem to kill these bacteria, they just cause them to reduce their metabolic respiration or go "metabolically silent" (shown very clearly in the paper). So they ummm hibernate but are still there. In the case of 5-asa's I'd tend to believe this is due more to a slight change in pH but could be wrong. Just a thought based on how bacteria respond to their "external" environment.
5-asa's seem to also inhibit sulfide production (from bacteria): gut.bmj.com/content/48/suppl_1/A82.full
So lot's going on in that department. I think 5asa's might thicken mucus as well. Not sure though.
L. Reuteri and L. Plantarum secrete specific antibacterial compounds that target and kill the bay guys. As well and more important they secrete both Serine and Threonine Proteases and these proteases do NOT break down the mucus (this surprised me).... They just form a biofilm and keep others in check. Have to dig this one out again... Can't find it at the moment.
They also reduce Tnf-a s-space.snu.ac.kr/bitstream/10371/30201/1/Ko-2007-Lactobacillus%20planta.pdf
- Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-α Search this if the link doesn't work.
This paper deals with the effects of Antibiotics on mucus thickness and how if under the right circumstances and say a pre-existing population of AIEC or any adherent type bacteria (there are lot's) can set things up for a very persistent infection. iai.asm.org/content/79/4/1536.full.pdf
Also again, remember all these bacteria (Adherent and Invasive) seem to be highly antibiotic resistant -even to Vanco and some of the big guns.
On a side note: The big drug company's have all pretty much stopped making new-antibiotics. All their efforts are focused on antibacterials. Something's fishy here. They're not telling the whole story.
Even more important - The above paper shows Metronidazole treatment compromises goblet cell function and inner mucus layer production... This will become incredibly important in a second - As I'll post a second mucus paper in a separate post under this.
I don't think this is going to be isolated to just Metronidazole. I would assume others will do the same.
Also we can't forget about
the fact that all these Adhesive bacteria do a few things:
1) They secrete a toxin that paralyses Leukocytes (White Blood Cells) - so they just walk right past them. I'll dig this one out as well and post when I find it. This goes back to the 10,00 biopsy paper and the picture of the wall of leukocytes. I believe (from memory) fragillis secretes this toxin the best. Though again I need to dig out the correct paper.
2) They all can invade our macrophages and/or epithelial cells - and they either induce inflammation (tnf-a) and/or they induce or prevent "apoptosis" depending on what they want to accomplish. All in all they hide out in our cells because our immune system won't attack them there. Then they replicate and move on. images.cell.com/images/EdImages/devcell/april/maurelli.pdf
3) They secrete a toxin (intercellular wise or in between or epithelial cells) that expands the gaps between our epithelial tissues as well. C-diff does this the best. Just search for it. Or see bellow fro C-diff and Confocal microscopy.
"Most likely this mucus layer (they are talking about
the inner most mocus layer here) is sufficiently dense with pores too small to allow bacteria to penetrate. Such a property is reflected in the insolubility of the inner mucus in chaotropic salts (guanidinium chloride) known to disrupt all non-covalent bonds. The only way to solubilize the inner mucus is to reduce (break) the disulfide bonds that maintain the polymeric net-like structure of the Muc2 mucin."
Further on they say "Entamoeba histolytica secretes a cystein protease that is capable of cleaving the human MUC2 mucin at a very specific peptide sequence. This is located at a position where there are no intramolecular disulfide bonds that can maintain an intact MUC2 network. A cleavage at this site disrupts the net-like polymer nature of the MUC2 mucin of the inner mucus layer, allowing the parasite to penetrate, reach the epithelial cells, and invade the host. Such proteolytic enzymes may also be found in some species of the human commensal flora."
Anyway - one still has to sort through Fact from Assumption or Highly Suggestive etc... And mouse from human and so on... But the pathway from mucus breakdown via antibiotics is very clear - same with food source/environmental chemicals. Just not proven "fact" much like everything else.
Oh and let's not forget about
our little buddies (Our third immune system). Once the mucus layer is thin - these guys have nothing to bond to and help keep us free from bacteria. newscenter.sdsu.edu/sdsu_newscenter/news.aspx?s=74269
Also one last thing. Here's an awesome one on C-diff and the expansion between. And more so they see other bacteria... www.plosone.org/article/info:doi/10.1371/journal.pone.0058753
Bottom line - at this point in time I'd bet everything I had that if you can get rid of the bacteria there would be nothing more left for the immune system to respond to. No more immune response = no more inflammation.
Autoimmune is not the case here... It's nothing more than a bacterial infection. The drugs we take just calm the reaction to the bacteria.. that's all.
Fixing the mucus barrier would be step 1. Killing these ba$tards step 2. Healing Step 3.
Post Edited (Canada Mark) : 11/2/2013 6:24:12 PM (GMT-6)