My latest UC theory-Call it part X

Canada Mark said...
Hmmm - ok... so there are people that were actually very healthy and did not take antibiotics... I really thought that would not be the case.

What about long intermittent bouts of IBS type symptoms prior - like just "D" and loose stools?

Or are there people that pooped perfectly normal one day and then awoke one day to see blood and mucus?

No blood or mucus, but I literally pooped normally one day and had diarrhoea the next. From that day forth I never had a normal BM again. Not a single episode of diarrhoea in my life before that, and I was 24 years old by this time. (Don't know if it's relevant, but I did have chronic constipation in my childhood/teens.)

Only taken one course of antibiotics, for a chesty cough which wouldn't clear up when I was 19.

As for the theory that IBD is a normal immune reaction to an abnormal gut dysbiosis, no; a normal immune system recognises antigens correctly and switches the inflammatory response off, instead of going to town attacking the contents of the bowel. You have Crohn's colitis and not UC, don't you? Well, Crohn's is now considered to be the result of a deficiency in the innate immune system. The macrophages are inherently faulty, which is what leads to the failure to clear out the crap from the gut wall.

jem.rupress.org/content/206/9/1839.full

Even UC may be an immunedeficient disorder rather than an autoimmune one.

www.ncbi.nlm.nih.gov/pubmed/21997382 - full article isn't free, which is annoying. So I can't read it.

Whether it's deficient or overactive, a faulty reaction with the immune system is involved somewhere. IBD seems to be caused by some insanely complex interaction of genes, the immune system, and the environment.

While macrophages may be faulty or UC may be an immunodeficient disorder, I believe  there is something causing it from the environment,epigenetic interactions,whatever.
Starting around 1920 our macrophages did not decide to get faulty on their own.
Old Mike

Post Edited (Old Mike) : 8/30/2013 12:02:05 PM (GMT-6)

I like the paper NicecupofTea posted as it's really quite interesting.

BUT, when you really read it thoroughly they are suggesting something: That at the root Crohn's Disease specifically there is is a problem with macrophages... Now... they haven't really proved anything as they point out in the end, just offer up a possible explanation through genetics.

What actually scares me again is this paper and the mode (some of the genes they speak of) what they are suggesting actually supports the "cellular infection" or whatever you want to call it. They even study the same bacteria! So it supports the Adherent and invasive Escherichia coli (AIEC) infection of Macrophages. Or the e-coli penetration into macrophages and the benefit they get from increasing or not allowing tnf-a to turn off basically.

Again here is the AIEC you can read and cross reference if you really, really want to get into it. www.nature.com/labinvest/journal/v92/n3/full/labinvest2011156a.html

There's quite a few other papers on this topic that outline the gentic switches that e-coli flip to accomplish this. That's why it may not be an autoimmune issue, just a different way of looking into it...

Again, it;s the e-coli in this line of research that is preventing the inflammation to turn off... because they use "our" inflammation for reproduction purposes. So easily mistaken for autoimmune because of the lack of "off"

Also there's an odd post on the forum about stomach acid in the colon... chlorine, coffee etc... I worked construction and drank a TON of coffee daily and nightly and drank water from the hose on site.

Though that really doesn't explain anything for the organic and healthy people.

@OldMike - Actually Crohn's likely first appeared 5-10 thousand years ago, with the advent of modern agriculture and strong selective pressure on a particular gene or allele - in the below link, 503f - which gave an advantage to those who had that particular mutation. The downside is that 503f, along with a combination of two other identified genes, also increases the risk of Crohn's disease.

blogs.discovermagazine.com/gnxp/2011/08/crohns-disease-is-about-barely-keeping-you-alive/#.UiDTX5LIUpQ

The upside of 503f is that it is a more efficient transporter of the antioxidant, ergothioneine. As a European with Crohn's, I probably have this mutation and therefore am a member of the enhanced transportation of erogothioneine master race. Go me.

Anyways, no, our immune system did not consciously "decide" one day it was fed up with doing its normal job and to stop working properly. It probably came about as a result of past genetic compromises which maybe helped some people at the time, and screwed up some of us in the present.

@freddyj - Yes, I know what you mean about it feeling like something just shifted; that's how it seemed with me as well :-/ I'm in a surgical-induced remission now, but I have Crohn's and I know something could trigger the return of that dread disease a second time just as suddenly as it did the first time. It's like a cloud hanging over my head. Anyway, I don't know the state of your current disease, but I hope you manage to get into remission. It is insanely complex and we all would have avoided the triggers if we could have done, so try not to stress out about not being able to find a cause :-/

@Canada Mark - The article never claimed to be anything other than a theory. But you need to understand the difference between scientific theory and other types of theory. Scientific theories are scrupulously rigorous. Scientists come up with a hypothesis as a possible explanation for something, then conduct experiments to test the accuracy of that hypothesis, and keep on conducting experiments. Over time, existing theories are either elaborated on and improved with new evidence, or discarded with lack of evidence. Over a long enough period of time, some scientific theories become so well-established that nobody except fringe lunatics believe they aren't true (the earth revolving around the sun, for example), but note that they are still called theories. There is always more to understand and learn; that does not mean what we know so far can be dismissed on the slightly contemptuous grounds it's only a "theory".

Sorry, that out of the way, it may be that they are on the wrong track with Crohn's and the innate immune system deficiency theory. Personally I don't think that they are, but it is relatively early days yet.

PS: Just wondering. Have you heard of Thomas Borody, an Australian gastro? He believes that Crohn's is a 'syndrome', or a cluster of infectious diseases.

www.scirp.org/journal/PaperInformation.aspx?paperid=19619 - you need a PDF reader to read this, but luckily this article is a fairly straightforward read unlike the genetics one ;p

I don't know why, I just don't really believe Crohn's is an infectious disease (perhaps a few cases, but not the majority...).

PPS: My brain is done-in now, so I'll read the AIEC thing later... :-/

Good history of IBD. I use this to try and develop timelines.

Old Mike

http://onlinelibrary.wiley.com/doi/10.1002/ibd.3780010103/pdf

Post Edited (Old Mike) : 8/30/2013 3:01:31 PM (GMT-6)

I understand hypothesis/experiment/theory/law quite well. I write these often for fluid dynamics to prove disprove them through software and on site testing/experiments. Same process, same review procedure, same chain of events, same end results. It's the papers that are produced based on experiments that overlooked or did not account, not only for all variables, but those variables that are directly associated with other processes/hypothesis. It's a common issue in research. i.e things overlap with other hypothesis that they did not account for/read in their experiment to prove, disprove or account for. In this case being autoimmune vs. bacterial infection. Which, or both are triggering/capable of triggering said event - in this case particular gene expressions. In this case neither papers prove or disprove so it's open to the readers interpretation until such time as one or the other is proven through further experiments.


That being said my internal bias (which we all have) is a goofy view of "autoimmune disorder" :

Nature is not dumb, and does not make mistakes. It always knows where the "off" switch is. And bacteria have had 3.5+ billion years to figure out how to screw with our switches.

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@OM - I like the selenium idea. I actually had a plumber suggest this to me three years ago! Including Vit E and I think fish (real fish, not oil). I said what the heck does a plumber know about Crohn's-Colitis.. haha... Quick to judge... bad habit. - turns out the plumber has a PhD in Chemistry but grew up old school working for his dad through school and enjoys the day day to day working with hands. I never tried it though as the guy is a little ummmm... odd... but maybe I should have.

I knew it was a mistake to check HW so shortly before bedtime -_-

Uh, nature makes mistakes constantly. Errors in DNA replication during cell division leads to mutations all the time. And from harmful mutations come diseases.

http://en.wikipedia.org/wiki/Mutation#Harmful_mutations

As for your first paragraph, you seem to be griping that the articles in question don't take into account multiple hypotheses and pit them against one another. Huh? Comparisons are suited to things where they can make that kind of comparative approach, eg results of various meds in treating a particular disease. It's not that hard to get the raw data by running several clinical trials.

But how on earth would you go about comparing one unknown factor to another unknown factor? Bacterial infection sounds about as simple as it gets, right? Except for when, even after decades of research, the offending bacteria still can't be reliably isolated and identified (hello there, MAP). Likewise, the mechanism by which the immune system causes IBD still cannot yet be fully described. You're not seeing the trees for the forest, to slightly re-word a popular saying.

Anyway, I absolutely must, really, beyond a shadow of any doubt, go to bed now. I'll have a look at the probiotics thing tomorrow (with about 5 other things :-/) but if I don't get enough sleep, I won't be fit for anything. Goodnight.

This crap keeps us all up into the wee hours searching for an answer... Or anything to get rid of the crappy feeling.

Actually replicating DNA is #1 top priority for cells. DNA base pairs are damaged all the time, but it's due to chemical processes within the cell itself and/or exposure to toxins and other external environmental sources (smoking etc) causing a "lesion" in the DNA structure. Not by mistake.

Oddly due to the 3.5+ billion years bacteria have have on us they are masters at recognizing, and fixing these.

Nature does some pretty darn cool stuff on it's own.

I'm off to bed to... BUT I want to read about this selenium thing a little further... or heck, maybe I'll get up early and go buy some. I'm running outa things to try anyway...

I think the saying is "throw enough S*&t at the wall and eventually something will stick"

haha

Hmmmm... Hey OM, I came across this while looking up Selenium:

www.hindawi.com/journals/ppar/2012/620839/

You may want to read and look down this path a little. I have not come across this before. It touches on a lot of common aspects that have popped up and ties into your breakdown of the mucosal barrier. ANd also ties into some of NiceCupOfTea's Immune Response side of things.

If I read this right we may want to look at things that increase PPARy expression, like probiotics, butyrate and so on.. and avoid other items than decrease expression. Though I'd have to read it a few more times to make sure this is the correct interpretation.

Post Edited (Canada Mark) : 8/31/2013 7:08:05 AM (GMT-6)

Again, the cell is not making the mistake during replication - it simply cannot... nature does not and cannot survive this way - by making mistakes. Nature does not make mistakes. It follows specific laws.

The "Mistake" or lesion as it's called is always caused by an external influence be it a chemical reaction inside the cell or an external influence from outside the cell. Over time cells have evolved error checking to try and overcome these influences and prevent/repair lesions.

It's the chemical reactions and external influences that cause error in replication leading to disease etc.

Really, the most amazing thing to think about is just how or when did a cell ummm even recognize that something "an external or internal influence" was causing replication errors and therefor it needed to evolve or incorporate an error checking procedure to try and prevent these.

Ok... maybe not THE most amazing thing, haha... but it's pretty darn crafty and cool of nature to come up with this procedure in the first place.

Post Edited (Canada Mark) : 8/31/2013 11:08:21 AM (GMT-6)

Too much good stuff came out today..

Old Mike

Quantification and Characterization of Mucosa-Associated and Intracellular Escherichia coli in Inflammatory Bowel Disease.

http://www.ncbi.nlm.nih.gov/pubmed/23989750