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My crazy theory as to why UC starts in the rectum.

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Posted 4/1/2016 3:08 PM (GMT 0)
Based on my history.

UC 1980,quit smoking in 1977.

Prior history none.

Now back in 1971 Nov-Dec, a good case of Korean craps,resulting in D for about 2 weeks.

One day with the burning D, I felt something tear and a burning sensation for about 3 days, went away

and did not think about it again.

Came home from Korea Jan 1972, got a rectal abscess which needed emergency surgery sometime

in the spring of 1972, since then ongoing abscess, fistula ect.

1980 my scopes showed ulceration at 6cm.

Old proctologist said the UC/proctosigmoiditis might be caused by the abscesses.

So have been thinking about this since then.

As we know UC starts in the rectum for many/most.

Ok so what might be going on, is that you get a small tare, resulting in a infection which you might not

even notice, or a big one resulting in a abscess.

The consequence of this is that now the blood/immune system has been directly exposed to gut bacteria,

without any of the controlling effects such as mucus, and proper antigen presentation by the colon,

to the immune system.

So now the immune system is primed to commensal colon bacteria.

This is a form of autologous vaccination.

Since the immune system is now primed,it goes after commensal bacteria in the colon.

Why it mostly starts in the rectum is perhaps, the infection is from rectal bacteria where the tare

was,so the immune system is primed for the rectal area rather than a more proximal location.

So in other words the immune system has lost tolerance to commensal colon bacteria, and specifically rectal bacteria, or stool that has different bacterial populations from proximal to distal.

You will find that one of the definitions of UC is a loss of tolerance to commensal bacteria.

One way to regain tolerance, or even perhaps the only way.

Oral tolerance.

That's right autologous, oral FMT.

I have a study on that, some I believe might have went into remission, have to find it.

I might think you need small, long term dosage as a way to induce tolerance.

Found it.

http://www.gastrojournal.org/article/S0016-5085(15)00448-5/fulltext


You can also see from the study the autologous bacteria population seems to go in the wrong direction.

But, I am not looking to correct the dysbiosis in stool bacteria,but to establish immune tolerance.

as you can see 20% of the controls went into remission.

The controls used their own poo, which means autologous.

I guess I have posted on this before, but worth a rehash.

Of course the dangers of oral FMT is infection, especially in the lungs, or if you vomit.


You might ask yourself why is there no cure except surgery.

Answer: You can't un-prime the immune system,unless tolerance to commensal bacteria is somehow reestablished.


Does this explain increased incidence in the west, or increased incidence from moving from east to west in the world,or increased incidence with a western diet.


Perhaps the immune system once primed, everything is still ok,until something such as diet,

induces leaky gut, then more bacteria or antigens are presented to the primed immune system

and a sever immune attack is induced.


Also the immune attack is specific to the rectal bacteria or distal stool bacteria,so

that is why you would want to use your own poo for FMT and not from someone else.


you can see here some of the ways the gut protects itself from commensal bacteria

but what if the chain is broken by direct immune contact in an abscess

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920680/



some oral tolerance info

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292724/


now read here where it says clinical and experimental evidence.

pay particular attention where is says lack of inflammation with diversion of the fecal stream to ileal or colonic segments. 

Cant find it right now but there is an old abstract on enteral feeding,which causes a large loss in gut bacteria,

which puts crohns into remission, the docs could not explain it. When they restart food the crohns inflammation

returns. This theory perhaps also explains what is going on.

LINK    ---click where it says link

Old Mike

 

Post Edited (Old Mike) : 4/1/2016 4:34:34 PM (GMT-6)

Posted 4/1/2016 6:35 PM (GMT 0)
I think you're right. Doesn't seem crazy at all to me.
Posted 4/1/2016 7:25 PM (GMT 0)
Cant see this being a viable option. We get micro-tears all along our colons every day and our immune system is exposed to commensals all the time. If this theory held any water, we wouldnt see UC start only in the rectum. Its not like all of our immune systems just happen to be primed against ONLY the bacteria there.
Posted 4/1/2016 7:49 PM (GMT 0)
Marauder:
Micro tears are one thing they are in the controlled environment of the colon,where there are
mechanisms in place that mitigate immune response to bacteria.

In a rectal abscess there are no such controls, so the full weight of the immune system is launched
to control the infection. So the systemic immune system now remembers that these bacteria are dangerous.

As I also conjectured above since it is a rectal abscess, specific rectal bacteria are involved.
Or if it is distal stool getting into body tissue then distal stool bacteria are involved.
The distal stool bacteria populations are different than proximal stool populations.

So if I am right the immune system is primed/vaccinated for the distal portion of the colon.
Yea sure there are other possible reasons, like blood flow,high concentration of bacteria in distal stool,
ect.
That's my take.
Old Mike

Hell, I will even give you a case of true autologous vaccination resulting in IBD.
In this person it started out UC like then switched to crohns like, why, I have no idea.
But I can speculate, in me the autologous vaccination is with distal stool bacteria probably from the outside
of the stool or rectal associated bacteria, with the girl, they used whole stool which may give a different
bacteria population.
Posted 4/1/2016 9:14 PM (GMT 0)
Fascinating stuff. Makes a lot of sense to me. Thanks for posting.
Posted 4/1/2016 9:51 PM (GMT 0)
I believe when I was in my early 20's I had my first abscess. This was well before any UC symptoms. I scheduled a doctor's appointment for a general physical and was going to ask the doc about it, but by the time I got in to see the doc, it had cleared up on its own...reabsorbed or whatever. I had no idea what it was at the time. Full blown proctitis didn't appear until 13 years later. I think your theory makes a lot of sense.
Posted 4/1/2016 11:04 PM (GMT 0)
Old Mike,
this sure does make some sense to me. Let's say, at least as much sense as anything else I have ever heard!
I first had bleeding hemmies about 8 months before I was diagnosed with UP.

I really appreciate your thinking and your posts. Please keep sharing your thoughts and theories!
Posted 4/2/2016 2:21 AM (GMT 0)
There was a member here, I think wierdal or something like that who did a home made oral FMT. I think it helped him. I will say though the yuck factor is pretty high with this method even if it is your own stool. I would still do it though if it worked.
thanks for posting oldmike!! I swear you are going to find the cure to UC!
Posted 4/2/2016 2:44 AM (GMT 0)
If at some point I decide to try it, it will be the triple gel cap method.
Will freeze what ever is made up for a long usage time.
Basically pack the stool in a small gel cap, insert it into a larger cap, then insert into a still larger cap.
Change latex gloves between cap prep.
Do not contaminate the next cap in the line.
This way at least you get it down your throat without contamination until it hits your stomach.
Still sounds dangerous even if you burp, or it somehow aspirates to the lungs.
But this method has been used in human FMT trials, I believe without adverse events.
Believe I posted the actual method sometime ago have to search for it.
I also suspect you need to get them frozen fast to prevent any water in the stool from dissolving
the inner caps, or they are using special caps that dissolve in stomach acid but just not water,
need to look into it more.
I am also guessing that if I do this, my wife has to be out of town or something.

Will have to go over oral tolerance induction again, for sure,how antigens are presented for

induction, ect.

It may also be possible that heat killed stool may work.

Then there is that old saying by Soupy Sales, of which many have never heard of.

Don't try this at home, kids.


VIEW IMAGE


more oral tolerance super complex

http://www.nature.com/mi/journal/v5/n3/full/mi20124a.html


OM

Post Edited (Old Mike) : 4/2/2016 5:48:44 AM (GMT-6)

Posted 4/2/2016 8:59 AM (GMT 0)
Possibly 1 path to one type of UC. This does not sufficiently address the incidence rate after large or prolonged antibiotic exposure, so there would seem to be other paths and/or types.

also, key species could be under-represented in the fecal matter after the immune attack. I am not convinced it needs to be autologus. we originally get our consensual population from early exposures, and new exposures from other hosts or tailor made probiotic cocktails seem like viable options to me.

I have always though solutions would come from probiotics.
Posted 4/2/2016 2:22 PM (GMT 0)
Well as long as I am on the subject of oral tolerance here is a new mess.

This type of e coli is increasing.

Oral Tolerance Failure upon Neonatal Gut Colonization with Escherichia coli Producing the Genotoxin Colibactin

Old Mike

http://iai.asm.org/content/83/6/2420.full

Posted 4/2/2016 3:13 PM (GMT 0)
OM: So youre saying this theory would only apply to people who got UC after a rectal abscess? Maybe, but that the number of people with a rectal abscess who ALSO have just the right genetic and environmental conditions to cause loss of tolerance is a very small cohort. Also wouldnt explain why UC like conditions wouldnt develop in the upper colon when abscess occur.
Posted 4/2/2016 3:27 PM (GMT 0)
Part of the issue is blood injected auto vaccination with fecal material was actually one of the first treatments for Crohn's Disease itself by Dr. Burrill Crohn. It worked pretty well according to him, but when others tried they could not replicate his success. He favoured surgery at some point thereafter, before he knew about recurrence after surgery. Then he passed away.

I think back to Dr. Chiodini's thoughts on loss of tolerance to commensal bacteria, where he wrote that article asking if this is the case, then why patchy? and so on...

Perhaps it's actually the inflammatory event that is more likely the environmental trigger or culprit versus loss of tolerance to commensal bacteria?

EDIT: Something to think about:

We also don't 'tolerate' bacteria. Even commensal bacteria. Same applies to food. We do not 'tolerate' food. To the immune system there is no difference between food, bacteria or virus. They are all foreign. What we do is develop regulatory T-cells that suppress the immune reaction - or counter balance and suppress the inflammatory response to that particular antigen that the immune system has deemed 'safe'.

Post Edited (Canada Mark) : 4/2/2016 9:31:21 AM (GMT-6)

Posted 4/2/2016 3:45 PM (GMT 0)
I was also just thinking there is a lot of cases of rectal/anal abscesses in things like diabetes and so on that these people do not go on to develop IBD. Maybe it would be dependant on the type of bacteria causing the abscess though. One never knows. ? but then that would imply a specific bacteria cause I guess.

Just thinking of stuff out loud really.
Posted 4/2/2016 4:30 PM (GMT 0)
Marauder: For all I know bleeding from hemies might also induce,since there might be immune
contact with fecal bacteria,by direct contact.
Yes probably genetic and other components involved.
Don't think there is anyway I can know who only has distal ulcers vs proximal ulceration, at onset.
But we do know that most UC starts in the rectum, then spreads proximal.

I was going along minding my own business at 32 years old, then one day bam,cant remember
if I had an active abscess at the time. But between 1972-1980 I had quite a few, with active leaking
tracks. My initial tear was mechanical back in 1971 I felt it happen.

CM:What Dr. Crohn did may act like an allergy shot, depending on the dose, the immune system
might go tolerant, so it might work both ways depending on the dose.

Why crohns might be patchy, don't know.

another interesting paper, if have gut infection when say as a kid lots of bacteria can translocate into blood


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733441/

never the less I still believe something different goes on with direct exposure of the blood/immune system

 that is not under the control of any gut protective mechanisms.
Old Mike

Posted 4/2/2016 6:10 PM (GMT 0)
Hmmmmm.... Well the if a bacteria (or virus or large peptide) bypasses the gut and goes direct to the blood there are two things that immediately happen:

1) The compliment system is activated in response. Compliment works like a chain reaction. In fact it is working 24/7 to protect us... believe it or not, water of all things (H2O) molecules are responsible for inactivating the chain reaction and keep it from killing us... Anyway the compliment reaction is first and virtually instantaneous. C1 activates C2 and so on... until something tells it not to to continue the chain reaction...

2) The type of antibody response changes. Exposure through our epithelial cells result in a secretory IgA (sIgA) response... which is more of a muted, broad spectrum type response. But in the blood it will result in an IgM, IgG etc response. It's called class switching. The result (change and type of antibody) is an increase binding affinity between the the antibody and antigen. The different antibodies have more binding sites. The type of antibody (IgG, IgM etc) binds more specifically (sticks better) and triggers a far more robust immune response with different chemokine release.

Perhaps the compliment/class switching could result in abnormal or more aggressive response to commensal bacteria that happen to get directly to the blood.
Posted 4/3/2016 4:28 AM (GMT 0)
First time here in a while. So you no longer believe Pravda's theory? Wow I'm shocked
Posted 4/3/2016 5:09 AM (GMT 0)
www.sciencedirect.com/science/article/pii/S2237936315000337

Read down to the discussion towards the end. Radical Induction Theory.
Posted 4/3/2016 10:33 AM (GMT 0)
I have actually thought of trying the oral tolrance to stool method...but the wprst case scenarios in my head always stops me from trying.

I have always wondered if the (non-beneficial) bacteria in the stool or pathogenic harmful bacteria in stool might spread to the non diseased areas of the intestinal tract!!!

This in turn might cause a more severe form of crohns or uc we have now!

Mind boggling..
Posted 4/3/2016 12:08 PM (GMT 0)
Homer:

Yes I still believe in Pravda'stheory, what I was trying to do was force remission without the use of meds

in in combination with many antioxidants, did not work for me. 

Pravda uses meds plus many antioxidants, seems to work better than just meds alone.

But for the first time since 1986 I was able to force a mini remission, of which I have now lost.

Using curcumin, and a very short pred course. In the past I have not seen any effect from short course

pred.

Mark:

 From your posted paper..

These findings showed that the topical effect of SCF depends on the concentration used and the intervention time. In all animals which underwent intervention with SCF, we could detect, through the histological study, the formation of a thin protective film covering the colon mucosa in most animals. This finding, coupled with the improvement of the degree of tissue inflammation, confirms the ability of this drug, in acting as a mechanical barrier hindering the contact between the epithelium with the existing flora in the intestinal lumen

 

Along with this there is also antioxidant action.

The more I read on the gut protective immune system, the more I realize that the protection

is so good that something has to go radically wrong for anyone to get IBD, even the genetic component

needs some other environmental component for IBD to happen.

Part of the story is broken immune tolerance to commensal bacteria,again this should not just

happen in the gut due to all the protective mechanisms.

My thinking is simply what are the consequences of breaking immune tolerance to gut bacteria, EX-GUT.


What I mean by EX-GUT is anywhere in the tissue outside of the gut immune control,such as an abscess

in muscle tissue.


Is it possible that all bets are off, you have now been auto-vaccinated against your own commensal

gut bacteria. Specifically rectal associated bacteria, whether from the mucosa, and or distil stool types.

In both cases the bacteria types will be different than proximal bacteria types.

Populations shift from proximal to distal.

But in the case of crohns, perhaps some proximal bacteria are also in the distal stool,who knows.


Even with this there may still be safety mechanisms in place.

Going over my history again, the first emergency surgery in 1972 was for a massive abscess.

No IBD. But still had a mess down there from other new smaller ones and constant leaking

fistula tracks, and this is after the surgery healed. 

So the first mechanical tear back in 1971 induced for me a chain of events, that I am still trying to deal with.


strange I decided to search google for auto-vaccination, this is my first hit.

seems back in 1929 they were using it to cure UC, if back then of course they could verify actual

UC as opposed to something else.


http://www.autovaccination.com/





Old Mike

 

Post Edited (Old Mike) : 4/3/2016 7:13:38 AM (GMT-6)

Posted 4/3/2016 6:22 PM (GMT 0)
By developing your own theory for why UC starts in the rectum, aren't you by definition disagreeing with Pravda's theory for why it starts in the rectum?
Posted 4/3/2016 6:56 PM (GMT 0)
Not sure, if I remember correctly he says ROS/peroxides in the basement membranes first.
Well if the immune system is going after bacteria, or trying to get to bacteria, it is going
to generate ROS/peroxides.

So complex, I think I need another 100 years,to figure it out.
Hopefully some smart doc, will figure it out within the next 3 days, or so.
Or it has been figured out and we don't know about it, buried in some old patent.


Or it is something stupid like excess salt.

http://www.jci.org/articles/view/81151?utm_campaign=impact_2015_november&utm_content=short_url&utm_medium=pdf&utm_source=impact

http://www.jci.org/articles/view/80919?utm_campaign=impact_2015_november&utm_content=short_url&utm_medium=pdf&utm_source=impact

Old Mike


 

 

Posted 4/3/2016 7:25 PM (GMT 0)
Part of the problem is also that when a cell (take a macrophage) for example does not follow the apoptosis (or autophagy) pathway to cell death, something else happens altogether. Necrosis - so basically the cell degrades in a sense and ends up releasing all of it's contents into the open (or blood). This causes unneutralized H2O2 and other ROS that were previously tucked away safe inside the cellular compartments to be released and cause damage, not to mention the release of cytokines and so on which leads to inflammation.

Necrosis is found in IBD as well.

So there are multiple reasons for the excessive oxidation, but none of which can be explained as direct cause.

However what we have learned on the board here though over the last few years, is that aside from anti-inflammatories, antioxidants seem to be very helpful to many. It's funny that neither on their own seem to be quite enough for most, but when the two are combined they seem to do the trick for many. Meds (anti-inflammatory like steroids etc) and natural, like curcumin, WOO, grape seed oil and a few other things.

I think many might benefit from taking a combined approach.
Posted 4/3/2016 11:01 PM (GMT 0)
Wow wow wow, I thought cucurmin was safe, and only turmeric gave me bleeding,well I cut myself
slicing a roast beef, small cut on fore finger. Bleed for 25 minutes, had to take a vitamin K 1 to shut it down. about 20 paper towels for a small cut. K1 is shut it down in 10 minutes.
Wow. Probably 5 months on 660mg a day curcumin.

Did not seem to increase rectal bleeding.

Perhaps why it helps colitis, increases blood flow.

But geese, minor surgery you would bleed out.

I had blood dripped all over the kitchen, up in my sink, compression would not stop it,

tried to stop with a bandage sopping wet, with blood. What a mess, it is only a quarter inch cut.


Old Mike

Post Edited (Old Mike) : 4/3/2016 6:41:31 PM (GMT-6)

Posted 4/4/2016 5:50 PM (GMT 0)

Old Mike said...
Not sure, if I remember correctly he says ROS/peroxides in the basement membranes first.
Well if the immune system is going after bacteria, or trying to get to bacteria, it is going
to generate ROS/peroxides.

IIRC, he suggests multiple factors, all of which we've heard before (poor western diets, increased stress, possibly something like long term RX drug use, genetic predispositions, etc) contribute to our cells (mitochondria) either overproducing H2O2 or underproducing the endogenous antioxidants required to neutralize them. This leads to excess H2O2 in the cell, which if not addressed eventually leaks out of the cell, and when this occurs in colonic cells, and in the rectum (which is usually pressing right up against feces) the environment is created where the H2O2 attacks the colonic cell wall, creates openings, and leads to antigen exposure. This then triggers the immune system which attacks the invading bacteria - but also unintentionally the cell wall itself. This then triggers the feedback loop that leads to UC progressing down the large intestine.

That's my understanding at least.
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