UCF researchers closing in on cure for Crohn's disease

[TjEisenman]

On news last night in Orlando. Interesting to say the least. Could somesome smarter than me answer this question. What is the bactieria MAP called. I dont understand what it stands for. Anyway enjoy

http://www.myfoxorlando.com/story/23936394/ucf-researchers-closing-in-cure-for-crohns-disease

 

[wild_one353]

professor borody from australia has been using a map elimination protocol using a combo of antibiotics and yes it has had some success, but he eventually started using fecal transplants as far as i understand. his first trial of fecal transplants in crohns was reported to american college of gastroenterology late 2011. im sure this is what has inspired researchers all over the country to perform 10 studys on fecal transplants scheduled for the next 3 years.

it is my opinion that fecal transplants will be found to be the cure in both forms of IBD.
and as that doctor in the video states, i agree that MAP will likely be foudn to be indirectly related to crohns disease, and that disruption sin normal bacteria to be the true first cause or direct cause of IBD. MAP is most likely a secondary phenomena or effect of having crohns, and not the cause.

 

[rollinstone]

I think FMT is gonna cure a lot of diseases, the microbiome is definitely where the future of medicine is going. Soon as they start curing disease we will probs get smashed by a comet though.

 

[kiny]

Naser's team is mostly occupied with detection of MAP.

Why do some teams find MAP in 80% of crohn's disease patients, why do some teams never find it.

Are we looking in the right places, in blood, in a biopsy, in tissue, fistula, where would MAP be.

Does it mean because they can't detect MAP in someone, they should not be treated for it. Leprosy can't be found in everyone, but they still get treated for it when they have the symptoms.

How is MAP related to E Coli, is one facilitating the infection of the other.

There's a lot of questions still.

 

[Crohn2357]

kiny, these are very obvious questions that needs to be answered. Do you have any idea about ongoing researches that investigating relationship between microorganisms(including viruses) and autoimmunity?
In time, humankind can understand better the symbiosis between microorganisms and mammal organisms. Also methods of detecting microorganisms in human body can improve with more research and technology.
I'm thinking that maybe the autoimmunity concept is defined completely wrong. Maybe the immune system is actually detecting something harmful for human body; but we can't understand it now. Maybe there is a matter or organism in human body that technology of humankind can not detect right now.

 

[kiny]

Autoimmunity requires a self-antigen though. You can detect this in UC, specific for the colon epithelial cells, which is why people with UC have non-discriminatory inflammation over their whole organ, you can not detect this in crohn's disease.

UC and crohn's disease are extremely different diseases and it is a real shame the term IBD is used.

Genetic mutations in crohn's disease are all related to autophagy and bacterial handling at the macrophage stage, innate immunity, genetic mutations in UC overlap with autoimmunity.

The persistent pathogen theory is specific to crohn's disease and it does not involve autoimmunity. It's the theory that a specific intracellular pathogen, has managed to survive in the host and as long as the host is unable to rid itself of the bacteria, you will have inflammation.

Why this is specific to crohn's disease and not UC is because the genetic mutations specific to crohn's disease (NOD2, ATG16L1, IL23, VDR) would result in compromised innate immunity, which is why a host with those mutations would never be able to rid itself of certain intracellular microbes without the help of antibiotics or other -> persistent pathogen.

.

The persistent pathogen theory is also unrelated to the "loss of tolerance to the microflora theory", the theory that our own body somehow decided to turn itself against it's own flora and the flora acts as some type of self-antigen. Which doesn't make a whole lot of sense since if that was the case you would have mucosal inflammation everywhere, you would not have patchy inflammation like in crohn's disease, nor would you have transmural inflammation, nor would you have fistula, only an intracellular organ is capable of causing so much destruction deep inside an organ.

And all genetic mutations in crohn's disease are in fact related to the handling of intracellular pathogens, which includes MAP, AIEC, food borne bacteria like listeria, salmonella, campylobacter, etc.

There has never been a disease in history where the body turned itself against it's own flora, there are enough safety brakes in place in the body for that not to happen. So this theory that our own flora or modulaton of our flora is somehow a viable road to treat crohn's disease is not something I'm very convinced of. Which is why I'm not a "fan" of fecal transplants nor do I have much hope for them. AIEC does bind itself to epithelial cells (while also invading macrophages) on the outer wall of the intestine, they live in such strong biofilms that a fecal transplant or modulation of the gut flora is carying water to the sea, it won't have a strong effect on the bacteria, it's capable of staying dorment in cells and won't be affected.

 

[Crohn2357]

Thank you for idea sharing.

 

[TjEisenman]

What is MAP?

 

[wild_one353]

Theoretically speaking, fecal transplants may correct the underlying extinction in bacteria that is found in ibd patients, which may be the cause of the disease itself through the bacteria's role in regulating inflammation.

here is a study that examined all the bacteria in human intestine to find the most potent inducers of anti-inflammatory proteins, coincidentally, the bacteria that they determined to do this the best, is the exact bacteria that is extinct in ibd patients, making a very strong theory that if we replace these bacteria in ibd patients, then this will lead to remission or even a cure. so far, we have some evidence that this is true.

these bacteria's natural presence in gut seem to be necessary for the human body tissues to express anti-inflammatory molecules, which tell the immune system when to turn itself off. if these bacteria are no longer present in the gi tract, anything that evokes an inflammatory response could trigger uncontrolled inflammation. Restoring the extinct bacteria in IBD patients could turn off uncontrolled inflammation, and possibly permanantly, and professor T.J. Borodys 2003 study of fecal transplants in U.C. suggests this is the case as all 6 patients have remained in remission without drugs for up to 13 years post fecal transplants, strongly suggesting, they are cured.

There are 10 studys being done now on fecal transplants and 2 have been completed. most of these studys are scheduled to be completed in 2014, so next year will be an amazing year for IBD patients i believe.


References-

Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
http://www.nature.com/nature/journal/v500/n7461/full/nature12331.html

Commensal Clostridia: leading players in the maintenance of gut homeostasis
http://www.gutpathogens.com/content/5/1/23



My thread on Fecal Transplants- http://www.crohnsforum.com/showthread.php?t=52400

 

[mnsun]

MAP is a shorthand for 'Mycobacterium Avium Subspecies Paratuberculosis', a bacteria of the mycobacteria genus. (not to be confused with other M. avium species) The Mycobacterium genus includes tens of subspecies, amongst them are well known pathogens such as M. Tuberculosis, M Bovis and M. Leprae--from the cforum wiki link in your first post.

I do think that some sort of triple antibiotic concoction is in the trial phases for treating Crohns.

I know I've had doxycycline, for deer tick bites (lyme), and it is also meant for some mycobacterium treatments, also. I fully expected it to aggravate my intestines but no problems were encountered. Though, I did take probiotics a few hours after doses, in case. Maybe it actually "treats", to a minor degree, crohn's too?

I think it will take a combination of anti-mycobacterium/plasma drugs and probiotics/FMT, hours apart, to simultaneously kill off and crowd out pathogenic flora.

 

[mf15]

This paper makes a lot of good points that MAP is the cause of
both diseases.
Old Mike
http://www.gutpathogens.com/content/2/1/21

 

[kiny]

This paper makes a lot of good points that MAP is the cause of
both diseases.
Old Mike
http://www.gutpathogens.com/content/2/1/21

"3) The age at which an individual is infected. It takes a smaller dose of MAP to cause either ulcerative colitis or Crohn's disease in a child as compared to an adult"

I think the reason why people get crohn's disease at young age is related to the activity of the peyer's patches at that age, which open a route for intracellular pathogens to enter into deeper tissue. I don't think it has anything to do with "doses of MAP"

The issue with suggesting MAP for UC is that the genetic predisposition for UC isn't related to macrophage handling of mycobacteria.

In crohn's disease many genes overlap with other mycobacteria diseases, specifically leprosy, in UC they do not.

It is a "reasonable assumption" that someone with crohn's disease would be vulnerable to a mycobacteria, in UC this is unexpected. There's no indication that someone with UC would be vulnerable to a mycobacteria, in crohn's disease, genetic mutations dictate that someone would be very vulnerable to intracellular pathogens.

In ruminants, MAP is very specific for the ileum. The terminal ileum is the place MAP and AIEC thrive, they're extremely rare in the colon.

.

Also, don't forget that many people carry MAP in their body and don't have crohn's disease, they seem perfectly capable of ridding themselves of this bacteria, which is extremely pathogenic in nature and causes a deadly disease in many many animals.

If MAP causes disease in some individuals, it's reasonable to assume that their genetic make-up predisposes them to infection, which is the case in crohn's disease, not in UC, there's no indication that someone with UC would be vulnerable to a mycobacteria.

Farmers are exposed to MAP all the time, and rates of crohn's disease aren't any higher than the general population.

IF MAP is a zoonotic pathogen causing disease in humans, it would need to be individuals that are vulnerable to specific mycobacteria, which would include people with crohn's disease, but not UC, and not the general population.

 

[Axelfl3333]

Throw bucket loads of money at it!

 

[kiny]

Another reason I would be careful to suggest that MAP is in any way related to UC, is the lack of response of UC patients to antibiotics.

We know people with crohn's disease react to antibiotics. You can make your case that it's related to the gut flora or a persistent pathogen, but I know there's a response to antibiotics, I have seen it on myself, people on this forum have responded to antibiotics, people in studies have responded to antibiotics.

In UC the response to antibiotics has been disappointing.

 

[mf15]

Kiny: you of course make some good points. I have UC .
Quite smoking 1977,UC 1980,but 1979 moved into our new house which I still live in.
1/4 mile from working dairy farm,drank their milk,breath the cow dung dust.
We also have a slaughter house about 4 miles away,they drive cattle/pig trucks through the center of town about 1/4 mile away.
Perhaps don't actually have to be infected to MAP,just react to the antigen
which is everywhere,milk,dust,water.
Who knows.
Old Mike
and as you can see MAP is everywhere,CD UC normals

http://www.ncbi.nlm.nih.gov/pubmed/21484317

well almost everywhere we need to try and watch Chile for emerging
IBD, seems Johne's started around 2004 in goats at least in this report.
I don't know about their cows. But if johns is an emerging disease in Chile
then the research docs should take a good look and see what is happening
with people.
http://www.johnes.org/handouts/files/KruzeSep-06.pdf

never saw this one before,seems TNF-A helps MAP to survive
http://www.ecco-jccjournal.org/article/S1873-9946(12)00017-7/fulltext

actually cows in chile 1958
http://www.scielo.br/pdf/abmvz/v63n4/33.pdf

Johnes was a new disease around 1890 or so as was the increase in IBD
starting 1900 or so in England.

 

[kiny]

never saw this one before,seems TNF-A helps MAP to survive
http://www.ecco-jccjournal.org/article/S1873-9946(12)00017-7/fulltext

http://www.crohnsforum.com/showthread.php?t=33582

they have shown this with 6MP too

Still though, this is in vivo, many many in vitro tests can not find MAP in tissue of crohn's disease patients. MAP tests are all over the place. I was tested for MAP, negative. I basically am not any wiser, since negatives become positives, and some people say it has to be tissue instead of blood, others say that testing like x is wrong and a test should be y, some culture, others don't both with cultures since it takes over 6 months to do it. etc

Even if antibiotics work for corhn's disease, or even for UC, that will not end the MAP controversy, since any number of pathogens could be killed by antibiotics.

Many diseases were cured long before the cause was known.

 

[kiny]

Johnes was a new disease around 1890 or so as was the increase in IBD
starting 1900 or so in England.

Right, the first cases we can be very sure of were in fact cases of crohn's disease (don't know about UC) were from a paper from 1913, from Dalziel.

Because in 1913 they could detect intestinal TB.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2345847/?page=10

 

[nogutsnoglory]

Has anyone tried these antibiotics separately at once? I know the clinical trials are examining all 3 in combo but I'd be curious to hear from non trial folks if there are any.

Speaking of antibiotics, I need one, are there any that may target MAP? I mine as well be on one that may help the crohn's too.

 

[kiny]

Speaking of antibiotics, I need one, are there any that may target MAP? I mine as well be on one that may help the crohn's too.

There isn't even one effective antibiotic that targets MAP, if it existed it would target slow dividing cells and we wouldn't need 3 but only 1.

Antibiotics that can target MAP would be azithromicyn, cipro, clarithromycin, rifabutin, rifampicin and a few others.

(notice that some of those overlap with tuberculosis / leprosy treatment, which are just like MAP, mycobacteria)

None are really that effective against MAP.

Mind you, these antibiotics target other bacteria too, cipro is used for crohn's disease as most know, and like most people know, this works for a while and then stops working for most people,...because....the reason all antibiotics stop working....resistance....... but cipro is also effective against E Coli for example.

 

[Samboi]

Either way - this is all good news.
It has given me a scrap of hope to cling on to.
Hopefully I can hang on to my colon long enough to derive the benefits of the research and maybe even a cure.
Exciting times we live in.
I hope 2014 is a great year for Crohnies!

 

[TwinkleToes]

I'm in Orlando and reached out to this Doctor about the study. He was very kind but unfortunately I do not qualify for the study as I have fistualizing Crohn's.

He did say that if anyone was interested and wanted to read more to go to Clinicaltrials.gov

 

[bigtruck]

Prof hermon Taylor from st georges hospital in London has been treating people based on this from 1985.

 

[michelle222]

This research sounds promising

Saw this online and thought it was pretty interesting. I've actually read about this idea that MAP is somehow the cause of Crohn's and, if they can prove it, this should help cure it. Sounds like they aren't 100% sure and it could still be a couple years before they know....but still it sounds promising

http://www.myfoxorlando.com/story/23936394/ucf-researchers-closing-in-cure-for-crohns-disease

There was also an article in Psychology Today about a woman who was treated using this theory and she is considered "cured". I got a little bogged down in the medical language but it sounds promising. I will keep my fingers crossed.

http://www.psychologytoday.com/blog/pura-vida/201311/is-there-cure-crohns-disease

 

[kiny]

They're not 100% sure because of 3 reasons I agree with:

1 they can not detect MAP in everyone with crohn's disease and some studies don't seem to find MAP at all in tissue. (as in, a study checks 40 people, and finds MAP in 0, another study checks 20 and finds MAP in 16)

(This could be down to detection methods, it could be because MAP is only causative in a specific crohn's disease demographic, or maybe crohn's disease has nothing to do with MAP)

2 histological differences between Paratuberculosis and Crohn's disease

(even though at first glance Ptb and crohn's disease look pretty similar, there are specific differences. It's a much weaker argument than the detection rates, since different pathogens create different diseases in different animals (even in Ptb, it actually doesn't always affect the ileum in animals, it can go to other places too like in pigs)

3 People in close contact with MAP, such as farmers, don't seem to have higher rates of crohn's disease.

.

On the other hand, there's also a whole bunch of reasons why you should suspect that MAP could be causative.

*Clinical similarities

*ileum involvement

*genetic predisposition to mycobacteria infection in crohn's disease patients

*the studies that do show higher MAP vs controls

*successful studies with macrophage penetrating antibiotics

*patchy granuloma extremely similar to other mycobacteria diseases

*rise of crohn's disease matching the rise of johne's disease in the beginning of the 19th century

*much higher prevalence of crohn's disease in dairy consuming regions

*many animals, including monkeys, get sick to the point of dying when they are infected with MAP, it's extremely pretentious when a doctor or farmer pretends humans would somehow be immune to this pathogen, MAP is a pathogen

etc

 

[Crohn2357]

http://www.zonade.com/aeii/DrTaylor/Treatment/RifClariCommentary02.pdf

 

[jazzsous]

Developed UC at the age of 17. Lasted 2 years. Treatment Valium. Lived in my family home at the time. Very rural. Up in the mountains. Gravity flow water from Mountain spring. Moved away from my family home at age 18. UC symptoms stopped a year later. Four and 1/2 years ago I quit my job and moved back to my family home to take care of my Mom who had Alzheimers. She died this last July. One year ago in October 2012 I started having symptoms and was Diagnosed last month at age 55 with Crohns. This paper makes a lot of sense to me in a number of ways. But then again I'm looking for anything that makes sense.