mycobacterium paratuberculosis

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FunGuy
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   Posted 2/1/2010 5:03 PM (GMT -7)   

I just received a new very good book about ibd's.  The book was published in 2003.  They mention that there was some thought that the above bacteria could be a cause of Crohn's in some people.  The book also states that this bacteria is prevelant in cattle. 
 
As I have said on the forum elsewhere:  My earliest recollection of having Crohn's symptoms started when I left the city to work on a Dairy in 1975.  Not to mention the amount of manure and me rubbing my eyes, nose and yup my mouth; I also drank a lot of unpasturized milk that was simply filtered through paper.
 
Anyone have any experience with this bacteria?  I don't believe any of the other kids got sick BUT of course not everyone is subceptible to the same bugs.

Ankylos
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   Posted 2/1/2010 5:39 PM (GMT -7)   
The symptoms are so similar that it certainly is evocative. Some of the anti-MAP antibiotic regimes work for some people, but there are questions about whether those drugs are acting on MAP, or some other bacterium.

There have been a pile of studies in which researchers have tried to find MAP with colitis, and they're about half and half; some that use excruciatingly sensitive techniques that seek out only the DNA of MAP have failed to find it reliably. That doesn't mean it's not there, but that there should be some strong questions about why it's found at all.

My angle is that MAP is related, but probably secondarily; it may colonize a damaged gut, maybe making things worse. But a few things are not readily explained:

1) Why does MAP not explode when immunomodulation starts? Screening for tuberculosis- another mycobacterium- is required before starting TNF agents. I've been told this has been explained, and I'm not done watching the Behr videos to discuss his explanation (it hasn't come up yet).

2) Why is there Crohn's disease in countries with little or no MAP? Africa has only one reservoir of MAP (some imported sheep, based on my correspondence with one wildlife pathologist in .za), but folks still get Crohn's in Africa. Admittedly, the rate seems lower, but that is probably because of diet; Crohn's was virtually unknown on the continent until the 1950s anyway- probably due to the absence of wheat in the diet. Similarly, some Australian states have little or no MAP, yet the incidence of IBD is similar to that of industrialized countries.

3) Why has nobody been "cured" of Crohn's despite aggressive antibiotic intervention? The anti-MAP protocols take years, and although some individuals have been placed into remission for some time, they are never cured of the disorder. Doing so with (non-drug resistant) tuberculosis is relatively simple in comparison.

4) Why does diet influence the disease so strongly? If MAP is a facultative intracellular pathogen, it should be relatively shielded by its "lifestyle" within the gut, yet some individuals are capable of controlling their disease with diet alone. Whether they're delusional or not is a matter of discussion, but- as this is not possible with with cattle equivalent (i.e., the end is almost always the same- death), why would they stabilize and improve even without drugs?

As for your dairy work- sorry to hear you got sick. However, I don't believe there's a correlation between occupation and IBD. One would expect that if this were a genetically influenced disease that was ultimately caused by exposure to the organism, it would be much higher in those that work on farms. I don't believe that's been demonstrated, and that's a data point that should have popped up long ago if it were the case.

broomhilda
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   Posted 2/1/2010 8:06 PM (GMT -7)   
Fun Guy- You may want to use the search engine here for "chocolate stains" posts. He has given us all valuable insight to MAP and research/therapies being used in Sidney, Australia if I remember correctly.
Dx'd Jan'06, 1st Resection 7/06, Humira, Imuran, B12 injections, Nexium, Lexapro, Nulev, Glucosamine, Multi-Vitamin, Calcium Citrate, Ultracet. Secondary conditions: Psorasis, Osteoarthritis, Fibromyalgia, Lactose Intolerant, gallstones, kidney stones, Carpel Tunnel & POST-menopausal (Hurray)


snohare
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   Posted 2/2/2010 2:46 PM (GMT -7)   
MAP is something that I am convinced is directly related to the incidence of Crohn's Disease and/or other IBD disorders.
nono I am however totally unqualified in bacteriology or microbiology of any sort, never having studied biology formally in any way after leaving school. My sources of information tend to be scientific magazines as background (and nowadays Wikipedia), with online science websites, online papers and fora such as these for leads and more detailed in-depth discussion of topics.
My only personal experience with MAP - if indeed it was, and I have no evidence to say it was, other than circumstance - was that of childhood visits to my uncle's croft where both I and my sister drank unpasteurised milk from his cow Daisy, who subsequently became ill with a wasting disease, and was sent to slaughter. A farmer down the road at whose farm she stayed on occasion (Daisy that is, not my sister !) was plagued by severe gut problems and sickly cattle; I don't know about the cattle but he was diagnosed with IBD, which in those days would have been about as detailed a diagnosis as could be expected.
To discuss the points raised by Ankylos a little further:
My understanding is that originally studies that looked (visually) for MAP in humans were done by researchers who had done work with other species such as cattle. They were looking for MAP as found in bovine species, and found none. Later however researchers who did not have experience of MAP in cattle found that MAP tran****ed into another, much smaller form in humans (spheroblasts, if I remember correctly) and hid themselves inside a particular type of cell called macrophages. Later studies were able to isolate genetic sequences that could be sought for and presumably thus found in any spheroblasts but not bovine MAP cells, due to the unusually impermeable, waxy cell membrane possessed by the latter but not the former.
I am not conversant with all the different studies, but I know that microscopy studies did find as much as 90% infection rate by MAP in IBD patients once the smaller cells were being searched for. It is always worth noting that many studies in medicine are plagued by poor design, and most particularly, by low numbers of participants, which can skew the smallest of chance variation and make it seem significant; this is one reason that epidemiology is so valuable in this sort of debate. Mark you, 90% is still significant in any book - if replicated.
1) Leprosy, TB and MAP are all genetic relatives; in the case of TB so closely that generic tests for TB in cattle which show "false positives" may in fact be pointing out MAP. (One wonders how much of the long running and vitriolic debate about TB in the UK, about badgers causing transmission to cattle, based on these imprecise tests, is based on false premises. It is known there is widespread presence of MAP in wildlife, watertable and soil.) I believe the reason that TB tests are done pre-TNF therapy because latent TB (which can lurk unseen for decades, a la MAP) once no longer actively opposed by the host's immune system, may run riot and cause irreversible damage.
The mechanism by which TNF therapies work is fairly well understood; they aim to reduce or short-circuit the inflammatory process which leads to increased Crohn's Disease activity. If these therapies are preventing or more likely reducing the creation of macrophages which are the habitat of MAP spheroblasts and which MAP needs in order to transform/reproduce/ or create an inflammatory habitat, then this explains why MAP would not increase dramatically in the same way as diseases using other mechanisms might - eg, TB. (This is all presumption, I am not sure how much evidence there is for this argument as I've never studied it in detail.)
2) I cannot remember where I saw this information, it was YouTube but not perhaps Dr Behr, but my belief is that MAP of a different subspecies (clade) has been found in bovine species such as buffalo, as well as ovine species (ie, sheep, goats, etc). This makes it pretty likely that there will be MAP in species endemic to Africa; not to mention, in the wildlife. (It is extremely widespread amongst mammals in the UK, as would be expected of a slow-acting pathogen with a normally small effect on the ability to reproduce successfully.) So there may be as yet unrecognised reservoirs of MAP that are less effective in infectivity and the lower incidence of CD may be a reflection of both this, and differences in diet - having a diet high in processed carbohydrates is hypothesised to have caused the huge rise in Johne's Disease that suddenly occurred in cattle in the latter half of the 20th century. If a diet high in simple starches/sugars does cause changes in gut mucosa or intestinal flora that predispose towards MAP becoming more infective, this would explain a lot - although an individual's genetic makeup is still obviously important, in humans at least.
3) As regards Australian states' incidence of MAP, I know nothing, so cannot add anything other than speculation. The genetic component will in theory limit the number of potential cases to a lower number here, compared to say the UK. My guess is the testing is poor, and MAP is taking advantage of the Westernised diet to cause IBD.
4) This question is the crux of the matter. Again, personally I have little detailed information on the effectiveness of these therapies; I know trials exist and are reputed to have high remission rates, and that is all. I haven't been able to find any data on long term outcomes or numbers in trials (very much a crucial part of any such trial; below a given number it is worthless statistically) but I can certainly hazard some guesses which are dismaying if true.
If (nono a big if ) MAP does cause a slow burn infection of the sort that TB was once famous for, and has a similar sort of cellular membrane in non-spheroblast form (another big if), then it would be as difficult to eradicate as TB used to be before the famous triple therapy that finally put all the sanatoria out of business. This is because for any drug regime to be totally effective, it would have to target two different types of cell physiology. The waxy cell membrane that TB has makes it very unusual; lots of substances simply cannot get through, making it hard to detect or kill - stains and antibiotics never used to interact with it, only once its intricacies had been fathomed were weapons found - but the cost is a relatively inefficient metabolism and slow reproduction. This means - yes, you've guessed - it takes a long time to totally wipe out MAP if there is widespread infection by this sort of cell as well as spheroblasts in the macrophages. Even assuming a treatment regime that attacks both, macrophages have a short lifespan, and are constantly being renewed; so any period where drug attack is less than 100% effective will provide a window for escapees to reproduce and find new hiding places. The good news here is that genetic variability is likely to be low due to the slow reproductive rate and the unusual cell membrane. But it is worth remembering that even today, many years after a "cure" for TB was found, there are people with latent TB who had it so deeply entrenched in tubercules, often in the brain, that it could never be eradicated, and they were simply put onto the paperwork as latent carriers; and occasionally they find the TB flaring up. Personally I think a bacteriophage is the best hope if such an infective agent is responsible for Crohns. ( eyes Don't hold your breath, this wouldn't be nearly so profitable as drugs at $10 000 a pop.)
4) I may be delusional, I believe that I control my Crohn's by diet ! But control is not cure; far from it. In fact I wouldn't even say that it is full control. What I feel is happening is a balance of power between my immune system attacking a pathogen (wouldn't we all love to know how it does that! ) and the pathogen hanging on and occasionally gaining ground. It is noticeable that whenever I take too much exercise - which in excess has been found in athletes to cause a depression of immune system activity - I not only suffer from severe fatigue similar to athletes "burnout", I also have a marked resurgence in CD symptoms which is virtually simultaneous. Going back to the theory regarding high carbohydrate diet, it is also very obvious to me now that I am on a low-sugar diet that one of the worst things I can do for my CD is consume large amounts of sugar, as I once used to do without a second thought.
And every so often, even when I seem to be eating exactly right, and not overdoing things, and being a good boy, I still find my Crohn's flaring up. I can find no earthly reason why, it generally doesn't last long, but it is very demoralising when it happens and a reminder that stalemate is not control, never mind a cure; in fact, the disease is controlling me as much as the other way around. yeah
The nutritional therapy that I was put on, which has twice led to impressive improvements, emphasised the importance of rebalancing the acidity of the stomach to minimise damage by pathogens and improve digestion, and improving intestinal flora and macronutrient intake for the same reasons. As Ankylos says, MAP may be a secondary infection, as may be many other as yet unidentified agents. It might even be that a single plasmid is to blame, and its presence is spread between not only clades but entire species, so that E.coli with a particular snippet of DNA cause the same sort of damage as C. difficile with the same gene. My personal inclination is to use Ockham's Razor and say that MAP has too many handy coincidences involving it to not be at the heart of things - but who knows, maybe it carries an infectious passenger, in the same way that cholera is carried within another bacteria in sea water... confused
Finally, if I remember correctly, dairy workers have actually been found to have a particularly low incidence of CD. This is actually one of the things that led researchers to look at cattle; often prior exposure to proteins or partial organisms belonging to a pathogen or its relatives causes partial or enhanced resistance to the disease it causes. (Think cowpox and smallpox.)
I think we need fewer drug tests and more basic microbiology. But hey, what do I know, I'm an unemployed labourer ? ! eyes

FunGuy
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Date Joined Oct 2009
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   Posted 2/2/2010 4:06 PM (GMT -7)   
Wow snohare that is some response:
 
Interesting points.  I wonder if the increasing incidence of Crohn's through the last century correlates with the increasing consumption of pasturiezed milk?  That could lead to fewer and fewer people getting that partial exposure to MAP proteins (like the dairy workers you mentioned) and not building up an immunity.  Supceptible indviduals could then contract MAP at some point from whatever source including poorly processed meat products and go on to exhibit sypmtoms of Crohn's.  I'd love to see that study done.
 
I stopped taking my prilosec two weeks ago in the hopes of increasing the acid level in my gut to "upset" micro-organisms.  After my EGD today the my GI is strongly urging me to resume the prilosec due to errosion in the esophagus.  I had no heartburn lately but I will take his advice as I trust his judgement.
 
Your diet control may not just deprive the organisms of preferred nutrition but may moderate or boost you own immune response to control your illness. 
 
You would think that there is enough pieces of intestine from us floating around that they have enough samples to disect and find these waxy cysts?
Thanks.  Hope work turns up for you soon.   Guy
 
 

FunGuy
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   Posted 2/2/2010 4:19 PM (GMT -7)   
Ankylos thanks you for your well thought response:
 
Points 1 & 3 are addressed by snohare I think.  Slow growth rates and impervious "cysts" that remain dormant could explain remissions without cure.
 
In answer to your point #2 i would suggest that there may be more than one cause for Crohn's and that the incidences in these areas are A) from another bacteria or cause altogether or B) from trips abroad, or imported food?  Just some thoughts
 
#4 Remember that people and cattle are two different species with two different immune systems.  There are MANY disease that kill one species (or individual person) while only being mild or simply carried by another species or individual.  ie. there are people who never brush their teeth and go through most of their lives without a cavity.  Diet control may not just deprive the organisms of preferred nutrition but may moderate or boost you own immune response to control your illness. 
 
These points don't nullify your thoughtful response but I think they leave the door open to the idea that MAP may indeed be ONE culprit in Crohn's.
 
my doctor told me today he has no way to test for this TB bacterium in the gut so that is on hold for a while.
 
BroomHilda thank you also I will do that search.


 


Ankylos
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Date Joined Jan 2010
Total Posts : 19
   Posted 2/2/2010 4:50 PM (GMT -7)   
There is a way to test for MAP in your gut, but it's not approved for human use. You you would purchase the MGIT test from B&D and run the test yourself. The main problem is- what do you do if you're positive? You can swallow all the antibiotics you like; they may suppress the disease, but nobody's claimed they can cure it in this fashion- even the triple antibiotic cocktail of Myoconda doesn't boast that.

I would recommend a couple of review articles on the subject; specifically, the Feller paper from Lancet Infectious Diseases (2007):

Lancet Infect Dis. 2007 Sep;7(9):607-13.
Mycobacterium avium subspecies paratuberculosis and Crohn's disease: a systematic review and meta-analysis.

Feller M, Huwiler K, Stephan R, Altpeter E, Shang A, Furrer H, Pfyffer GE, Jemmi T, Baumgartner A, Egger M.

and the Mendoza article from 2009 (World J Gastroenterol. 2009 Jan 28;15(4):417-22. Mycobacterium avium subspecies paratuberculosis and its relationship with Crohn's disease. Mendoza JL, Lana R, Díaz-Rubio M.). Mendoza elaborates on how antimicrobial therapy has failed to resolve CD. The .pdf is here:

http://www.wjgnet.com/1007-9327/15/417.pdf

As for gastric pH: I would suggest that consuming fewer carbs will really knock back the heartburn. I went from swallowing Tums like candy to needing them twice in the past two years, once I got the carbs out of my diet.

EMom
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   Posted 2/2/2010 5:05 PM (GMT -7)   
Ankylos said...
1) Why does MAP not explode when immunomodulation starts? Screening for tuberculosis- another mycobacterium- is required before starting TNF agents. I've been told this has been explained, and I'm not done watching the Behr videos to discuss his explanation (it hasn't come up yet).


Ankylos, I hope you find it there! It's been a couple of years since I was reading and listening to everything MAP-related that I could get my hands on. It's possible that I have confused it with another interview--possibly John Hermon Taylor? Borody?. My apologies if it wasn't Dr. Behr!

FunGuy
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   Posted 2/2/2010 5:28 PM (GMT -7)   
Thanks again Ankylos. Incredible people on this forum.
 


broomhilda
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   Posted 2/2/2010 9:02 PM (GMT -7)   
Well, I for one am certainly not ready to throw the baby out in the bath water.  My father was institutionlized for 2 years with TB at the age of 16.  He felt he contracted it in one of two places...you guessed it...a dairy farm, drinking unpasturized milk and/or going swimming (where mama said not too) less than a block away from where a regional hospital was sitting on the river.  This was back in the early to late 30's.
 
My uninvited neighbor at the last home we owned was property which the county siezed and promptly installed a wastewater spray site.  The evening/morning breezes did not blow directly towards our house, however, the buffer line was 100ft from the nearest dwelling, i.e.; my house.  We also had a pool.  During my daily pool chemical checks (usually done in the a.m.) I would find my deck covered with a rather slimy film, hence airborne pooh!  We also live in a hurricane prone area and quite often the holding tanks would overflow during a hurricane or heavy rain.  Oh, I forgot to mention we were on well water which the county tested as "safe".  Less than a year from the installation of this wastewater site, I was becoming symptomatic.  Two years from the date of installation I was diagnosed with CD.
 
Strange coincidence(s)...I am not convinced.  Genetically speaking...MAP could have been a factor with my illness as well.  So I'm hanging in there until some more light is shed on this debate!

snohare
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Date Joined Oct 2004
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   Posted 2/3/2010 4:51 AM (GMT -7)   
To answer in reverse (anyone who has seen me driving knows I need all the practice reversing I can get !):It was Dr Harmon (sp ?) who cited the epidemiology studies in Wales where they investigated the higher incidence of CD in particular valleys. The factor they had in common was that they all ran in the same direction, and were subject to aerosols from windborne spray from a local reservoir. They took samples from the reservoir dam, which was covered with a nasty blackish gunk - lo and behold, 'twas a biofilm containing MAP.yeah
Anyone who knows about biofilms, let alone the waxy cellular membrane that TB et al have, will appreciate that the chlorine in the pool will have had diddlysquat chance of handling any infective agents contained there with 100% efficiency. Not even chlorine would handle biofilms well unless used neat...nono something I think you would have avoided, broomhilda ! And to cap all that, you can be sure that because culturing for MAP in vitro takes 16 months and a huge amount of patience and skill, they would not have been testing for it.
Sorry folks, I have a dog here nudging my arm, I must go out into the snowy wastes and play catch ! tongue

jpnutritionfirst
Regular Member


Date Joined Apr 2009
Total Posts : 383
   Posted 2/3/2010 6:34 AM (GMT -7)   
I too believe in the map theory. I wanted to respond to some of the points against it made already
1) Why does MAP not explode when immunomodulation starts? Screening for tuberculosis- another mycobacterium- is required before starting TNF agents. I've been told this has been explained, and I'm not done watching the Behr videos to discuss his explanation (it hasn't come up yet).

MAP and TB are both mycobacteria but they are not identical bugs. In fact, MAP has no miliary phase, meaning it doesn't spread throughout the body in a rapid fashion like TB does. Also, there is a theory that Remicade actually binds to TNF on the surface of infected cells thus killing the dormant infection.

2) Why is there Crohn's disease in countries with little or no MAP? Africa has only one reservoir of MAP (some imported sheep, based on my correspondence with one wildlife pathologist in .za), but folks still get Crohn's in Africa. Admittedly, the rate seems lower, but that is probably because of diet; Crohn's was virtually unknown on the continent until the 1950s anyway- probably due to the absence of wheat in the diet. Similarly, some Australian states have little or no MAP, yet the incidence of IBD is similar to that of industrialized countries.

The studies trying to detect MAP are varied. If the study didn't use the proper technique -- using PCR on gut mucus and not blood, also looking for the IS900 sequence as per Dr. John Herman Taylor-- then it's hard to put any weight on this information. Genetics also plays a role in who is susceptible even if the bug is everywhere.

3) Why has nobody been "cured" of Crohn's despite aggressive antibiotic intervention? The anti-MAP protocols take years, and although some individuals have been placed into remission for some time, they are never cured of the disorder. Doing so with (non-drug resistant) tuberculosis is relatively simple in comparison.

Again, TB and MAP are not the same bug. We are using drugs targeted for TB against map. Clearly they don't work very well.

4) Why does diet influence the disease so strongly? If MAP is a facultative intracellular pathogen, it should be relatively shielded by its "lifestyle" within the gut, yet some individuals are capable of controlling their disease with diet alone. Whether they're delusional or not is a matter of discussion, but- as this is not possible with with cattle equivalent (i.e., the end is almost always the same- death), why would they stabilize and improve even without drugs?

Diets have never been proven to work.
Crohn's Colitis diagnosed 6/08
Organic SCD since 4/09
Remicade since 6/09
Boswellia + Natren's Healthy Trinity probiotic + Cinnamon + Wild Oregano Oil + vitamin D + zinc + Barlean's fish oil
Remission


snohare
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Date Joined Oct 2004
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   Posted 2/3/2010 8:41 AM (GMT -7)   
Back again. A thousand rabbits will dream twitchily tonight, as will the rabbitless dog. :-)
Ankylos, thank you for the links to those papers, I look forward to reading them. ( I know, I need to get out more - the dog keeps telling me! eyes) Who are B & D ? An American company I presume ? I'm very interested in getting this test done, assuming it has good false positive and negative rates.
I'd agree with you regarding the carbs; and it is interesting that I had a duodenal ulcer which my GP considered related to my high-carb diet, years before the CD became so obviously active.
My nutritional therapist (an unregulated term if ever there was one) specifically said that too much wheat, salt and sugary products had collectively not only depressed my immune system but eventually had the effect of diminishing the acidity of my stomach, enabling poorly processed chyme and unkilled pathogens to enter lower reaches of the gut and wreak havoc there. What most impressed me about my initial consultation with her was the fact that she was able to tell me what my history of symptoms had been, and furthermore have a coherent, cogent theory of what processes could variously cause and reverse those effects. (And no mentions of quartz or quantum energy, either. wink) The difference between her and any GI I have ever seen was enormous; the difference between a worm's eye view of soil, and a farmer's; symptomatic treatment versus holistic therapy.
nono One thing that the therapist repeatedly emphasised was that there were many different ways to end up as I did, and every case would be different, with a different treatment regime. I ended up with the distinct impression that the workings of the gut and immune system are like a computer, they can be configured in a myriad of ways using numerous inputs, with intestinal biota being particularly important. So absolutely no contradiction or confirmation of the more conventional multiple causes theory there.
Given that certain breeds of dog are prone to Crohn's Disease, I wonder what work has been done by veterinarians or other researchers, to look for MAP in dogs ? If it is found in dogs and can be used to fulfill Koch's Postulates by being taken from a canine CD host and used to infect a CD-free host, that would be a very important step forward.
FunGuy, the correlation that seems to be hypothesised regarding cattle is not that a rise in incidence is related to pasteurisation, but rather that as soon as highly processed high-carb diets began to rise in popularity amongst cattle farmers (they were used to create rapid weight gain) there was an explosive increase in Johne's Disease amongst cattle, where previously it had been very rarely seen. Pasteurisation certainly does not eradicate MAP, although in the UK it has now been modified to reduce the numbers of MAP that may survive. In the US, where the pasteurisation process has not been modified due to resistance from the dairy industry, homogenised milk from herds of 500+ is seemingly (according to sample statistics) virtually guaranteed to contain MAP. This sounds like a recipe for soaring numbers of CD cases (as seen), especially if eating meat from Johne's Disease-d cattle sent to slaughter can cause infection; but bear in mind that MAP is widely prevalent in groundwater and wildlife, and a simple mutation that affects efficiency of transmission would have the same effect. In the UK there is a scheme to eradicate Johne's Disease in herds in the Shetland Isles,
very low key with no publicity at all; it will be interesting to see what result this has on IBD incidence amongst the local human population, if any.
As is usual in science, at every turn of the debate the cry is, "We need more facts !" yeah

newfoundsun
Regular Member


Date Joined Nov 2009
Total Posts : 145
   Posted 2/3/2010 1:15 PM (GMT -7)   
Just an interesting point here:  I talked with a doctor who had Crohn's and was treated with the MAP antibiotics.  At the time of our correspondance just a few months ago, it had been five years since her treatment, and she was at that moment sitting in Costa Rica, in a run-down bar, eating local food, and drinking a beer with ice in it.  She says that MAP cured her of Crohn's. 
 
Interesting.......
newfoundsun
 
http://www.newfoundsun.wordpress.com/  (my blog about this journey I have just started)
 
CD diagnosed 11/12/09
Seeing a Naturopath and modifying my diet, so far

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