Defective mucus sugar. Chicken or the Egg problem perhaps solved

Sorry did not mean to put this in the old thread.

I pulled this out of one of my zillion mucus threads.

Chicken or the egg,worth another read by everyone.

Might explain why everyone does not get UC.

We still have the question why the defective sugar.

Old Mike

http://omrf.org/2011/04/11/omrf-finds-defective-sugar-root-colitis/

mucus viscosity increases distally

http://www.ncbi.nlm.nih.gov/pubmed/19300126

Post Edited (Old Mike) : 10/30/2014 9:33:56 AM (GMT-6)

All this stuff has been in this thread since the get go.

Here is what might really be going on,my speculations,which might not agree with 98% of mainstream medicine.

My latest thought is that once you get a mucus breach which for some reason

is not repaired quickly enough,the bacteria just keep coming and coming,zillions and zillions of them.

Leukocytes are overwhelmed,immune cascade starts then you are screwed.

After re-reading the 10000 biopsy paper it hit me.

This is not like a normal cut,which can be easily walled off by the body and the bacteria killed off.

In this case the wall is the mucus barrier.

Or much of the infection is walled off in the ulcers,but the ulcers are denuded of mucus.

As you can see in this case,the body would have a difficult time fixing this,since it would

appear that the mucosa is not meant to contact large amounts of bacteria.

So as I have been saying a few times this week,UC is not auto immune nor an aberrant immune response,

to commensal bacteria.

Its a normal immune response to a massive amount of bacteria,possibly 10000 different types.

Not sure of course if it is just mucosa  associated bacteria, stool bacteria or both.

Pred thickens mucus.

Smoking thickens mucus.

Antibiotics thin mucus.

NSAIDS and 5asa not sure anymore.

NAC thins mucus.

Butyrate thins mucus.

Bacterial protease thins/destroys mucus.

Old Mike

 

Post Edited (Old Mike) : 7/4/2014 1:04:24 PM (GMT-6)

Maybe you've come across this before?..

Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulcate sodium:link.springer.com/article/10.1007%2Fs00795-011-0550-7

And this
www.eurekaselect.com/104694/article

Stumbled on the mention and I was curious what the heck it was.

The Role of Intestinal Epithelium in Inflammatory Bowel Disease and Inflammation Related Intestinal Cancer J. Jasper Deuring PDF

If you copy this into google it's the first one that pop's up. Again, it's not your cup of tea I don't think, but there is some interesting stuff really.

Here is the fixed link for the one I was curious about or if you've come across it:
Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulcate sodium: www.ncbi.nlm.nih.gov/pubmed/23001296

I've never heard of Irsogladine...

Side note: In regards to the bifo bacteria one, in my particular case I tired to add it (Bifidobacterium bifidum) again a few days ago. This is the third trial and every time by the second day I start to feel discomfort and then a small amount of mucus appears. Stop and wait about 24 hours and things clear up. Other on here take it with no ill effect.

I could't access the full paper but I'm pretty sure this applies directly to it: - The sugar removal aspect.
www.ncbi.nlm.nih.gov/m/pubmed/3030298/?i=5&from=/2221078/related

Post Edited (Canada Mark) : 7/4/2014 6:26:46 PM (GMT-6)

1) Does anyone have a link to the 10,000 biopsy paper? Or at least know the name of it so I can find it myself?

2) Something that may be of interest to you guys. An experiment that I was a part of in the fall found that administration of NOD1 and NOD2 agonists resulted in an increase in goblet cells. We didnt look into whether or not this translated into increased mucus production, but it wouldnt be much of a leap to think it would.

Retinoic acid suppresses mucus production.

Will see if I can go anywhere with this.

Old Mike

http://dmm.biologists.org/content/5/4/457.full

beta carotene

http://www.sciencedaily.com/releases/2012/05/120501134414.htm

http://www.ncbi.nlm.nih.gov/pubmed/3475230

Probably not going anywhere.

Post Edited (Old Mike) : 7/6/2014 10:24:17 AM (GMT-6)

Hi there,

btw, I have regular contact with Dr. Swidsinski and if you have any questions please let me know. I recently discussed FMT with thim and he was rather curious and expressed his anger about this new trend. From his perspective there will be some deaths caused by this treatment which will become apparent by class 1 trials.

Best
GermanOne

marauder, if you're interested in all this stuff - why don't you maybe try looking at, or into, the effects of NOD1 and 2 on "types" of mucin released - so acidic (sialomucins and sulfur mucins) or neutral mucins.... that might be pretty darn interesting.

-------------

OM - I'm sure you have these but:

Mucin depletion in inflammatory bowel disease.
www.ncbi.nlm.nih.gov/m/pubmed/2318990/

Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.www.ncbi.nlm.nih.gov/m/pubmed/8150346/

-----------

Here OM - Please read this pretty carefully. I've been working on updating my goofy website with other studies that might back-up Swidsinski's study - and your thoughts on surfactants and recent viewpoint. This all comes about from the CHOP thing where they tested in un-inflammed tissue of UC patients - indicating a possible defect in us with IBD to clear bacteria.

I was going through my notes and found a older study that I marked but didn't read until just now.

In regards to the actual 10,000 biopsy paper study two things stand out:

First from the early unpublished paper that you link to: Page 3 it states this;

"Although adherent bacteria were present in nearly all (94%) IBD patients who had not been treated with antibiotics, the highest concentrations of mucosal bacteria were found, not in the inflamed regions of the intestine, but in less or macroscopically non-inflamed regions." So this is speaking of bacteria making their way into the actual epithelial cells....

Now, in the final published version it deals with this aspect of the study as they could not be certain these intracellular bacteria where not a result of the biopsy proceed itself:

"In Swidsinski's published study it states that bacteria within tissue were often seen at biopsy sites that were mechanically damaged but not at the sites where the epithelial layer was intact in. For this reason, tissue invasion was impossible to discriminate from contamination by fecal bacteria that invaded tissue cracks caused by the mechanical pressure of the biopsy forceps while they were dragged through the endoscopic canal. "

So this aspect was a little in question. Was the intracellular bacteria present a result of the actual biopsy?

This is what I had earmarked to read (and probably didn't because the title wasn't so special or intriguing:

Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo: www.ncbi.nlm.nih.gov/pmc/articles/PMC3002833/#!po=15.6250

This study answers that very question and show's that yes, bacteria in IBD patients are found intracellularly a lot more often than controls. BUT please note that they qualified IBD patients for this study in clinically and histologically verified CD or UC in clinical remission. ALSO - Note the Distal aspect

This is a very, very significant finding.

Especially that tissue invading bacteria can be found in normal people, but not that often.

This obviously raises quite a few questions.

Post Edited (Canada Mark) : 7/6/2014 8:24:03 PM (GMT-6)

MarK: You have a big thread on this very subject,wade through the whole thing again.

I take note of what is going on in the rectum.

My distillation of all of this.

 It seems to me that in normal people there is not intramucosal bacteria,implying no mucus weakness or breach.

While in 14% of normal there is intramucosal bacteria ,but no immune reaction,thus a sidestep of the immune system.

In the case of UC,in non inflamed areas with intramucosal bacteria,they are evading the immune response,perhaps

the immune system has found them in the ulcers.

Still boils down to weak mucus initially,breach,whatever,the bacteria should not be there.

Old Mike

https://www.healingwell.com/community/default.aspx?f=38&m=2896386

here is one abstract I pulled of interest,the same thing might be going on in the colon

where these microcolonies do not provoke immune detection and evade host immunity.

http://www.ncbi.nlm.nih.gov/pubmed/22801011

PS:Just to show you how serious I am about mucus, I am stopping my VO Manhattens, which I have one

most every day. Alcohol messes with the transferases which build mucus. But did not drink them when I got UC,as

far as I remember.

Post Edited (Old Mike) : 7/7/2014 6:19:23 AM (GMT-6)

Well, as long as the bacteria remain intracellular they are somewhat safe... this is the preferred method (vs. adhering to the cell) for the majority of bacteria anyway. They can then hideout and replicate. Our immune system can't "see" or even sense them for the most part so it makes them not accessible to antibodies which would normally tag them for destruction if they were outside the epithelial cell.

And they all have their little niches or types of cells then can gain access to so they are limited in how far they can get into us. So they don't become a "systemic" issue and kill us. Or fast I guess one would say. We would die from say toxic mega-colin as a consequence.

Certain fragilis strains and a few others release a toxin that paralyses some of our immune cells (leukocytes) as well - so they can march right on by. Maybe the leukocytes in the 10,000 biopsy paper all lined up might be blind to the one's sneaking by and entering the cells BUT are really there lining up and protecting from all the other bacteria in our guts... especially if there's a mucus barrier problem. Makes more sense from that viewpoint. So the soldiers line up in place of a proper mucus barrier. A defensive move to counter a defect.

Our epithelial cells live for about 4 days. Bacteria on average replicate every 20 min. 1 turns in to 2, 2 turn into 4, 4 turn in to 16 inside of a single hour. So one lucky bacteria that actually sneaks in can turn into well... a heck of a lot over 4 days. Then when the cell naturally dies they are released and wham - all heck brakes loose from the immune response for a bit and a few remaining work into other cells... and the cycle repeats.

Something like that.

And it's not like there's only a few cell in our barrier - I looked it up cause I was curious and there's an estimated 5 × 10^10 ! Just in the colon! One-sixth to one-third are shed every 24 hours and this makes for ~10^10 exfoliated cells per day. That's a heck of a lot of replicating and a heck of a lot of releasing potential...

So just like you suggested - an all out war. Normal (and intense) immune response to a whack load of bacteria. Type thing. Add all the negative effects of the actual immune response itself and it's actually a little scary what could be going on down there.

--------

I guess the bottom line, at least for you and others with Ulcerative colitis is you have a reduction/loss sulfurmucins corresponding to disease activity and this seems to be either the main factor or a direct consequence.

What doesn't make sense to me yet is why "b.fragillis" makes up >60%-80% of the biofilm imaged in UC when their dominant food source might be from breaking down sulfomucins (organic sulfur released from the cysteine). The cysteine bonds at the end of mucins are like the jail bars that keep bacteria from being able to get through. A loss in sulfomucins would seem to hamper a b.fragilis biofilm - not promote. Unless of course the reduction is actually from them directly breaking breaking down. So a consequence of a b.fragilis biofilm itself - like eating all the sulfomucins as they are actually released. Sulfomucins are highest in the distal colon - and they are predominantly present at the upper part of the crypts as shown in the first paper I posted on the recent sulfur farts thread. This is exactly where the fragilis biofilm is imaged in the 10,00 biopsy paper.

This thought then makes me think of Sulfate Reducing Bacteria - The presence of these corresponds to an increase in sulfomucin release from globlet cells n the distal colon. A severe excess of these perhaps initially creates a all you can eat sulfurmucin buffet for b.fragilis to thrive and become pro-dominant and just keep on eating all the sulfurmucins as they are released.

Like a one-two punch.

I don't know.


As for me with Crohn's-Colitis I cannot figure anything out other than it appears I may have thicker/normal mucus but far more intracellular bacteria. To be honest I've never spent much time even reading about Crohn's-Colitis specifically which is kinda weird.

Maybe this is why the combo of WOO and Imuran work so well together for me - whereas just one might not do the trick.

Who the heck knows... Sure do learn a lot of interesting stuff at least.

Post Edited (Canada Mark) : 7/7/2014 11:10:47 PM (GMT-6)

MarK or anyone else.
I am a little confused on what they mean by intramucosal.
What I think it means is that the bacteria have penetrated the mucus layer, and that they are in the crypts, and possibly between the colon cells, but not necessarily inside colon cells,or intracellular.

There is also a possibility there is something like this going on in the colon from mouth bacteria,subversion

of the immune system.

http://www.upenn.edu/pennnews/news/gum-disease-bacteria-selectively-disarm-immune-system-penn-study-finds
Old Mike
PS:After they pulled my sons colon I asked the gi doc if there was anything remarkable in the pathology,he said yes,there was no bacteria in the crypts. Perhaps the 12 antibiotic pills he had to take the night prior to surgery,killed them all, I have no idea.

Post Edited (Old Mike) : 7/8/2014 4:53:10 AM (GMT-6)