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View Poll Results: Is Mycobacterium Avium Sub-species Paratuberculosis the cause of Crohn's disease?
Yes, Koch's postulates have been met, it is therefore proven to be the cause 11 32.35%
Maybe, I need more proof 16 47.06%
No, the cause of Crohn's is unknown 6 17.65%
My gastroenterologist tells me it isn't the cause and I believe her/him 0 0%
I don't know what MAP is 1 2.94%
Voters: 34. You may not vote on this poll

 
07-23-2014, 05:11 PM   #1
JMC
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Is Mycobacterium Avium Sub-species Paratuberculosis the cause of Crohn's disease?

Ever since the discovery of Crohn's disease it has been speculated that a pathogen, Mycobacterium Avium Sub-species Paratuberculosis (MAP), was its cause. What is your view?

I have created a new thread here, to catalogue the latest MAP research

Last edited by JMC; 09-06-2014 at 04:33 AM.
07-23-2014, 08:28 PM   #2
D Bergy
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From my own experience, MAP is a major player in Crohns, but probably not the original cause. I would expect more cases of Crohns if it was.

My best guess based on what I have personally found in treating myself is another pathogen that is the root cause. I suspect Mycoplasma pneumonia or another strain such as Mycoplasma fermentans alters the immune function. Once that has been accomplished, exposure to MAP or an already present exposure becomes a chronic infection.

The MAP secretes mannose, which feeds various strains of E-Coli some which are harmful strains. All three pathogens can produce symptoms that are common to Crohns. Crushing fatigue, and strictures seem to be the work of mycoplasma directly, but it is possible MAP contributes also.

I also think that Crohns is only one disease that results from the original Mycoplasma infection. Once the immune system has been compromised, a person can contract any number of pathogens, and diseases.

One other pathogen involved in my Crohns is H-Pyori. It may just be a coincidental coinfection, but it makes symptoms worse.

To sum it up, something compromises the immune system first, which allows a common pathogen to flourish in the body, that normally would not. The rest is just a chain reaction from there.

Of course it is just my hypothesis, but I think it is close to correct although it probably is not complete.

Dan
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07-23-2014, 09:48 PM   #3
xeridea
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I think there is something there in MAP secretion of mannose disrupting phagocytosis and interfering with macrophage function. Seems that this may inhibit clearance of pathogens and contribute to immune deficiency. This is all over my head but there are papers out there regarding this topic. Maybe someone who has a grasp on molecular or cellular biology can chime in. Some articles I can reference are (please decode since site doesn't allow me to post links yet)

www dot ncbi dot nlm dot gov slash pmc slash articles slash PMC2213176

and

onlinelibrary dot wiley dot com slash doi slash 10.1111 slash j.1348-0421.2006.tb03782.x slash full.
07-25-2014, 03:55 PM   #4
David
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I do not believe it is the cause, no. I do believe that in some people, MAP may contribute to disease activity and controlling it would help. I'm certainly open to being wrong, however.
07-25-2014, 04:09 PM   #5
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If it can do it in cattle (Johne's), I reckon there's a good chance of similar in humans.

As for low numbers of cases in humans. Maybe it just requires particular genetic mutation(s) and a little bad environmental luck. Perhaps Crohn's is actually a number of diseases and one of them is a vulnerability to these, and perhaps other similar, bacteria?

My gut feeling(!) is yes. Let's hope we find the answer asap.
07-25-2014, 04:10 PM   #6
JMC
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I do not believe it is the cause, no. I do believe that in some people, MAP may contribute to disease activity and controlling it would help.
What evidence do you base that on David? Do you have an alternative hypothesis? MAP as the cause of Crohn's is supported by a huge amount of scientific literature and even in the last 6 months the supporting evidence has continued to grow. What is more exciting is that we now have the tools to prove this one way or the other, so I expect a definitive answer in the next 1-2 years.

07-25-2014, 04:13 PM   #7
JMC
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Perhaps Crohn's is actually a number of diseases and one of them is a vulnerability to these, and perhaps other similar, bacteria?
It will be like peptic ulcers, 90% of cases will be caused by something like MAP, and all the rest by a variety of different causes.

07-25-2014, 04:19 PM   #8
David
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JMC, admittedly, I haven't read many studies in the last year or so. If there have been some good ones you think I should read, please link me. And yes, I have an alternate theory but it is just a theory.

Let me ask this. If MAP is the cause, why does enteral nutrition help so much in the treatment of many cases of Crohn's?
07-25-2014, 05:21 PM   #9
AJC - Australia
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can I chime in on the enteral nutrition?

The Crohn's gut can get to a physical state where it cannot digest anything other than liquids…that is why this diet helps, because the gut is so ulcerated, narrowed and compromised.

What causes that narrowing and ulceration?
It isnt diet.
Once the gut is inflamed and ulcerated, diet can make the symptoms worse and/or better…but what causes the problem in the first place?

Every gastro on the planet will tell you there is
- a bacteria or environmental component
+
- a genetic component

we know there is a genetic component….it is proven

so, what is the bacterial component?

Why the resistance to the MAP bacteria when it has been proven via Koch's postulates (a legitimate scientific method) and it has been proven to invoke crohns like guts in mice and cattle. Dr Naser is citing 85% of the gut tissue he has operated on and tested for the MAP bacteria are positive, IN THE GUT WALL…living below the surface, compared to 20% of tissue from bowel wall biopsies.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064085/
under the entry 'CULTURE OF MAP FROM CD PATIENTS' (page 8 of 18)

The error that a lot of people are making with MAP bacteria is they foolishly assume that if the MAP bacteria causes crohns is one patient, it must cause it is 100% of patients to be the root cause. This is false. If you look at stomach ulcers and helio pyori, it was the CURE!!! yes?? OK, well in 95% of cases it was the cure but there are another 20 odd bacteria that cause the other 5% of cases.

The evidence for MAP bacteria being definitively linked to Crohn's is only a few baby steps away…they are going to prove or disprove it in the next two years and with the names of John Hermon- Taylor, Dr Saleh Naser and Dr Thomas Borody all behind it, i think we less educated folk would be foolish to dismiss the possibility that they are correct!

I hope to god that the MAP bacteria is the answer, it is the ONLY thing that offers anything like a cure. Of the treatments available, John Hermon-Taylor is the man with a vaccine - the other doctors are still working on long term anti biotic treatment.
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I believe this could cure crohns disease.

-Dr John Hermon -Taylor is trying to cure Crohn's disease.

Last edited by AJC - Australia; 07-25-2014 at 05:59 PM.
07-25-2014, 07:20 PM   #10
David
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can I chime in on the enteral nutrition?

The Crohn's gut can get to a physical state where it cannot digest anything other than liquids…that is why this diet helps, because the gut is so ulcerated, narrowed and compromised.
I agree that the digestive tract of people with Crohn's disease can have problems with digestion and absorption. But why is enteral nutrition putting some people into remission? THAT is my question.

Why the resistance to the MAP bacteria when it has been proven via Koch's postulates (a legitimate scientific method) and it has been proven to invoke crohns like guts in mice and cattle. Dr Naser is citing 85% of the gut tissue he has operated on and tested for the MAP bacteria are positive, IN THE GUT WALL…living below the surface, compared to 20% of tissue from bowel wall biopsies.
As I mentioned, I wouldn't be surprised if MAP play a role in the disease activity of some people with Crohn's. They may take advantage of a certain condition or conditions. But that doesn't mean they are the CAUSE. If you kill MAP and the condition that allowed MAP to become pervasive and contribute to the disease state persists, then you haven't cured Crohn's disease. As Louis Pasteur said, "Bacteria are nothing the terrain is everything”.

As I've mentioned, I'm all for being wrong though. And if I'm correct and MAP is just contributing to the disease state of some people with Crohn's, all this research is still incredibly important. Because if it is contributing to disease state, then proper control of MAP may indeed alleviate symptoms or even help people achieve and maintain remission.
07-25-2014, 07:51 PM   #11
D Bergy
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The terrain quote is actually a reference to what Pasteur supposedly said on his deathbed. This is a concession to his competitor Bechamp who was the proponent of the terrain theory.

Pasteur was a proponent of the germ theory.

I don't feel either is exclusive. Both theories can coexist nicely and there is evidence for both.

Dan
07-25-2014, 10:35 PM   #12
D Bergy
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I do think a MAP vaccine would be quite helpful for some Crohn's sufferers. There are a lot of ifs and buts involved.

If MAP turns out to be the original cause and the vaccine is effective, it will help many. However many vaccines that exist now are not all that effective. So there is that problem.

Assuming the vaccine is effective, when an immune system altering bacterium is present for a long time, it creates its own ecosystem which promotes other pathogens that would not normally flourish. Often creating a biofilm of symbiotic bacteria that would not exist in these proportions in the general population.

In other words your whole biology has been altered by the presence of the original pathogen. Especially if that pathogen alters the immune function. It would be overly simplistic to expect that immunity to MAP would cure all ails. It may help in varying degrees depending on the individual but the same ecosystem is present in the body.

Some diseases are complicated, and from what I have gathered this is one of them.

I hope I am wrong, but that's not how it looks to me at this time.

Let's hope for the best.

Dan.
07-25-2014, 11:14 PM   #13
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There is no debate on this subject. You cannot argue scientific fact. Koch's Postulates are the criteria for designating a certain bacteria to be the cause for a specific disease. They have been met.

http://www.ncbi.nlm.nih.gov/pubmed/3803136

MAP causes Crohns.

And to David,

I think it could be a number of things. Lack of carriers for MAP to continue to wreak havoc on the body, lack of energy sources for the bacteria to thrive on. I think you could make the same case with SCD. Why do some people get better? Maybe bread feeds the bacteria, or acts as some type of energy source for the bacteria. And when you remove that factor the disease goes away. Who knows.

It is a good question, but that question doesn't change or disprove Koch's Postulates.
07-26-2014, 12:26 AM   #14
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Are there reliable diagnostic tools for detecting MAP in CD patients? If you cannot irrefutably prove that MAP is the causative agent, you'd be hard-pressed as a researcher to casually throw it around. It has huge implications for cattle and dairy industries. For example, the 2013 value of the beef industry in U.S. alone was close to $90 billion, and dairy about $40 billion.
07-26-2014, 12:49 AM   #15
AJC - Australia
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there is currently no reliable diagnostic test for detecting MAP bacteria in Crohns patients…but Dr JOhn Hermon-Taylor and Dr Saleh Naser are bother very close. All Hermon - Taylor needs is funding to complete his diagnostic test, he is based in London.

Dr Naser has funding in the US and is also close to having a diagnostic test.

I think Hermon-Taylor needs about $500, 000US, a sixth of what Crohns and Colitis Foundation America raised last weekend.

Wouldnt you think one of these associations would cough up the money and lay this bacterial theory to rest, or prove it is the cause of Crohns disease?

The worst thing that ever happened for the map bacteria theory was the flawed clinical trial in Australia in 2007, because many doctors and most skeptics still cite that human trial, even though it had major holes in its method.
07-26-2014, 01:01 AM   #16
AJC - Australia
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I agree that the digestive tract of people with Crohn's disease can have problems with digestion and absorption. But why is enteral nutrition putting some people into remission? THAT is my question.


As I mentioned, I wouldn't be surprised if MAP play a role in the disease activity of some people with Crohn's. They may take advantage of a certain condition or conditions. But that doesn't mean they are the CAUSE. If you kill MAP and the condition that allowed MAP to become pervasive and contribute to the disease state persists, then you haven't cured Crohn's disease. As Louis Pasteur said, "Bacteria are nothing the terrain is everything”.

As I've mentioned, I'm all for being wrong though. And if I'm correct and MAP is just contributing to the disease state of some people with Crohn's, all this research is still incredibly important. Because if it is contributing to disease state, then proper control of MAP may indeed alleviate symptoms or even help people achieve and maintain remission.

I like where you are coming from David and it is true…change the environment and the Crohns symptoms change. Maybe whatever the bacteria is (MAP for example) maybe it thrives off processed sugars, starches and things not found in liquid diets….?
Then again, people who have incredibly healthy diets get crohns.
People with crohns who go on the liquid diet persist to have symptoms.
There def isnt a one size fits all..
07-26-2014, 01:58 AM   #17
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EN does put people into remission. Im sure my GI said a big problem was that a flare up often occurs soon after the diet is stopped. Perhaps EN attenuates the MAP population through some starve/support other bacteria/support the immune system route. Since it's intercellular maybe you'd need EN for a year or two? If MAP is so prevalent in showers, food and water anyone who struggled to clear it would just become reinfected I guess.

All speculation really. It's a shame the vaccine can't be fast tracked to the very seriously ill. And it's pretty worrying that MAP is our food chain anyway. Why haven't they vaccinated cattle or tried to stamp it out? From a precautionary perspective it seems crazy. I won't be happy if it turns out to be the cause. At least in one sense, anyway!

Update: I meant 'intracellular' :-)

Last edited by Karma; 07-26-2014 at 08:42 AM.
07-26-2014, 02:33 AM   #18
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Report on the BBC of a new virus discovered in human gut.scientists exploring genetic material in intestinal samples uncovered the CrASsphage virus.they say the virus could influence the behaviour of some of the most common bacteria in our gut.
Scientists say these type of viruses called bacteriophages ,have been shown to play a role in chronic diseases.
07-26-2014, 08:22 AM   #19
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If MAP is the cause, why does enteral nutrition help so much in the treatment of many cases of Crohn's?
http://www.eat-real-food-paleodietit...-and-SIBO.html

"Elemental diet

An elemental diet is a like a pre-digested formula that contains pre-digested carbohydrate (glucose) and pre-digested protein (amino acid) as well as some fat. If you choose this approach, you would need to replace all of your meals with the formula for at least 2 to 3 weeks. The goal is to starve the bacteria. Although studies show that this method can be very effective at eradicating SIBO, the benefit is usually only temporary if dietary changes are not made. Elemental diets taste awful and can also be very expensive, costing at least $900-1350 per treatment (rarely covered). (3-4)"
07-26-2014, 08:27 AM   #20
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EN does put people into remission. Im sure my GI said a big problem was that a flare up often occurs soon after the diet is stopped. Perhaps EN attenuates the MAP population through some starve/support other bacteria/support the immune system route. Since it's intercellular maybe you'd need EN for a year or two? If MAP is so prevalent in showers, food and water anyone who struggled to clear it would just become reinfected I guess.

All speculation really. It's a shame the vaccine can't be fast tracked to the very seriously ill. And it's pretty worrying that MAP is our food chain anyway. Why haven't they vaccinated cattle or tried to stamp it out? From a precautionary perspective it seems crazy. I won't be happy if it turns out to be the cause. At least in one sense, anyway!
I've emailed CCFA about this, and I did not hold back. The fact that sick animals with johnes are allowed to enter our food supply and there are no laws or regulations prohibiting their entry is an absolute disgrace. Especially with the research out. I mean, kochs postulates were proven 20 years ago! The US prides itself on the "safety" of its food supply. It is very far from safe.
07-26-2014, 05:08 PM   #21
AJC - Australia
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I've emailed CCFA about this, and I did not hold back. The fact that sick animals with johnes are allowed to enter our food supply and there are no laws or regulations prohibiting their entry is an absolute disgrace. Especially with the research out. I mean, kochs postulates were proven 20 years ago! The US prides itself on the "safety" of its food supply. It is very far from safe.
CCFA - in my opinion - wont write back to you, wont write about anything to do with MAP bacteria and moreover they have a vested financial interest in Crohn's disease and they probably dont want a cure. Bitter pill to swallow, but that is my opinion after numerous attempts to communicate with them. I dont think CCUK or CCAustralia are any better, in fact they might be worse.
07-27-2014, 01:02 PM   #22
mf15
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Just too add a little something,on the elemental diet putting people into remission,then once they start eating the disease may return.
Does not need to be live MAP, the MAP antigen is also in milk, and perhaps other foods.
That being said in early onset crohn's they are finding bacterial dysbiosis,which is not the
case in UC. Using an elemental diet would ten to change populations of bacteria,refeeding of course they would grow.
With UC the dysbiosis comes later.

The Faroe Islands have the highest incidence of IBD in the world, too bad I cannot get Johne's disease statistics from there. But they are were a colony of
Denmark, pretty high IBD incidence, and high Johne's disease in herds.
Australia also high IBD and Johne's.
Johne's first classified 1895, IBD history indicates incidence of
IBD in UK started to increase late 1890's early 1900's.
http://www.johnes.org/history/index.html
Old Mike

Last edited by mf15; 07-27-2014 at 01:33 PM.
07-27-2014, 01:10 PM   #23
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What would normal food provide fuel wise that would allow bacteria to thrive that an elemental diet would not?
07-27-2014, 01:35 PM   #24
mf15
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Changed by post to say populations of bacteria. But still might suspect rapid absorption
by the intestine may alter what is left for bacteria to feed on.
OM
http://www.ncbi.nlm.nih.gov/pubmed/22622202

EEN
http://www.hindawi.com/journals/grp/2013/482108/

as you can see here something is going on with the bacteria metabolism.

http://www.ncbi.nlm.nih.gov/pubmed/23016828
07-27-2014, 05:56 PM   #25
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This article studied how bacterial load effects macrophage recruitment in CD patients. It suggests that up to a certain level, there's normal cytokin recruitment, but at elevated loads, there's some inverse relationship where recruitment rates fall below levels of the tolerated loads.

EEN supposedly has nutrients absorbed in first 20% or so of the small intestine. This leaves the bacteria in the remaining 80% of the small bowel and pretty much the whole of the large bowel devoid of any significant energy sources, and thus a natural reduction in numbers. If the bacterial level goes below the threshold implied in article above, it would make sense you get into a range that results in "normal" cytokin recruitment and the inflammatory response normalizes.

I'll leave it to another thread but I prescribe to the school of thought that CD is an auto-inflammatory disease that is primarily an innate immune system dysfunction, and is distinct from UC which may in fact be an auto-immune disease like Celiac and RA.
08-12-2014, 04:40 PM   #26
AJC - Australia
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JMC, admittedly, I haven't read many studies in the last year or so. If there have been some good ones you think I should read, please link me. And yes, I have an alternate theory but it is just a theory.

Let me ask this. If MAP is the cause, why does enteral nutrition help so much in the treatment of many cases of Crohn's?
Hi David,
I took time out to ask professor Hermon-Taylor about this and his reply is below…..thoughts? If you 'PM" me i can send you the pdf paper?

'The answer is in the attached paper para "Inflammation in CD caused by a two tier co-operative pathogenic mechanism". The segments of gross inflammation are not caused by a direct head-to-head confrontation between MAP and the immune system, as in TB. The primary enabling cause is because MAP infection which is throughout the gut, dysregulates the immune and enteric nervous systems which makes the gut leaky.'

'The secondary effector cause is the perturbed neuroimmune response to entry into the gut wall of microbiota and food residues from the gut lumen.
Enteric feeding eliminates the allergic and other responses to the food residues as well as changing the nature of the gut microbiota.
When you stop the enteric feeding the whole thing comes back because the underlying MAP infection and perturbed neuroimmune systems are still there.'
08-13-2014, 11:54 PM   #27
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Don't know if the benefit of EN is nutritional, EN increases ceacam-6 production, and bacteria bind to it and it acts as a decoy. But if it really puts people in remission, I don't know personally. No studies that have rutgeerts score for EN, only CDAI studies, don't know how reliable they are. I use EN, but I have my doubts that it's able to put people in remission.

There were many studies that said helminthic therapy helped. Was debunked by a large study showing it does not. Crohn's disease was caused by too much hygiene, that's why we had unbalanced Th responses and everything could be explained by the hygiene hypothesis. That's why Africa didn't have CD, that's why richer families had more CD, it all made sense. People linked videos of GI explaining it all, they were convinced it was an unbalanced Th response caused by too much hygiene. Well, none of it was true, helminthic therapy failed.

There were many studies that said probiotics helped. In the last 2 years there have been a handful of large studies that showed that probiotics don't seem to help.

So, how accurate are those small EN studies, not sure.

If EN does anything, I think it would be because it increases ceacam-6 proteins, ceacam-6 binds to AIEC. Not sure why, but I do not think it is because of it's nutritional value.

Last edited by kiny; 08-14-2014 at 12:16 AM.
08-14-2014, 12:33 AM   #28
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http://gut.bmj.com/content/34/9/1198.long

This is one of those studies that people use to say EN is just as good as steroids. It only lasted 4 weeks, which by remicade standards isn't even enough to see initial healing with an endoscope in most cases. The patients within those 4 weeks who achieved "remission" actually relapsed faster than the steroid group, so within less than 4 weeks, people who were in "remission" with EN were relapsing faster than the steroid group. The study itself used DAI scores. But the conclusion was....that EN was just as effective as steroids, even though the remission didn't last 4 weeks, and steroids kept people in remission longer, but the abstract brushes it off and it's not talked about, it's only found in the data.

After 1 year, only 1 of 11 people on EN were still in remission. While 6 of the 19 on steroids were still in remission.

But the conclusion is still that EN can replace steroids, regardless that it doesn't keep people in remission.
08-14-2014, 11:34 AM   #29
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'The answer is in the attached paper "Inflammation in CD caused by a two tier co-operative pathogenic mechanism".
The paper is available online here

The review by Campbell, Borody and Leis, in 2012 is also very useful. Borody is stongly of the opinion that there is little evidence to support the view that Crohn's is caused by an abnormal immune reaction to the natural gut microbiota. He lays out the case for the proven pathogens, including MAP, and the need for better tests and treatments for them all.
08-14-2014, 12:14 PM   #30
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causation is a tricky concept. IT's not so linear, its a complicated set of events and relationships between biological entities.

I would say the cause of crohn's disease is damage to the microbiome which then allows a bacteria like MAP to flourish and cause greater levels of inflammation, in a similar way to other similar Gi disease, like C. difficile infection which presents itself with similar symptoms like never ending diarhea and occasionally inflammation. The microbiome is a collection of organisms(99%bacterial) that naturally live in our intestinal tracts to keep us healthy. There are other pathogens that are implicated in crohn's other then MAP, look up studies on Adherent Invasive Eschercia Coli (AEIC) in relation to crohn's and you'll see it goes beyond just MAP. So considering all this information, i believe The one and only true cause is damage to the microbiome from missing bacteria which would inhibit the growth of these organisms, and only a fecal Microbiota transplant can correct this. This is why we are starting to hear reports in journals now that people have been cured from FMT, having no symptoms of the disease some 25 years after their FMT for some UC patients, and 12 years for some Crohns patients. The variable results of the efficacy of FMT is due to variables that are not yet fully understood, as we learn more about how to restore damaged microbiomes with FMT, the success rates will improve. As for now, its hard to deny their potential with some people walking away completely cured, also the undeniable evidence that IBD patients also have missing bacteria that regulate inflammatory responses.

http://www.ncbi.nlm.nih.gov/pmc/arti...025/figure/F2/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868025/
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