CARD15/NOD2 mutations in cattle correlate to Johne's disease susceptibility

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Illini
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Date Joined Dec 2007
Total Posts : 298
   Posted 10/19/2008 7:56 AM (GMT -7)   
Not sure if this has been posted before but I got it today in my Pubmed weekly saved search. I'm still at home so I have not been able to read the full article.
 
In a nutshell: NOD2/CARD15 mutations are known to play a role in susceptibility to and severity of Crohn's.  The authors looked at mutations in these same genes in cattle, to see if they affect susceptibility to Johne's disease. And they found that having a certain mutation was associated with a higher likelihood of infection. This is good news for anyone who believes that MAP plays a role in some cases of Crohn's.
 
The abstract, with important parts bolded:

"Paratuberculosis represents a major problem in farmed ruminants and at the present is considered a potential zoonosis. The disease is caused by Mycobacterium avium subsp. paratuberculosis, and susceptibility to infection is suspected to have a genetic component. Caspase recruitment domain 15 (CARD15) gene encodes for a cytosolic protein implicated in bacterial recognition during innate immunity. Crohn's disease (CD) is an idiopathic inflammatory bowel disease in humans comparable in many features to bovine paratuberculosis involving an abnormal mucosal immune response. The association between mutations in the CARD15 gene and increased risk of Crohn's disease has been described. The objective of this candidate gene case-control study was to characterize the distribution of three polymorphisms in the bovine CARD15 gene and test their association with paratuberculosis infection in cattle. Three previously reported single nucleotide polymorphisms (E2[-32] intron 1; 2197/C733R and 3020/Q1007L) were screened for the study population (431 adult cows). The statistical analysis resulted in significant differences in allelic frequencies between cases and controls for SNP2197/C733R (P<0.001), indicating a significant association between infection and variant allele. In the analysis of genotypes, a significant association was also found between SNP2197/C733R and infection status (P<0.0001); cows with the heterozygous genotype were 3.35 times more likely to be infected than cows with the reference genotype (P=0.01). Results suggest a role for CARD15 gene in the susceptibility of cattle to paratuberculosis infection. These data contribute to the understanding of paratuberculosis, suggest new similarities with Crohn's disease and provide new information for the control of bovine paratuberculosis."

http://www.ncbi.nlm.nih.gov/pubmed/18926647?dopt=AbstractPlus


July 2007 Drug-Induced Liver Injury
January 2008 Crohn's Ileitis
Currently trying...
Entocort, Enteral Nutrition, Omega-3 (Flax Oil and Fish Oil), VSL#3, Vitamin E


Illini
Regular Member


Date Joined Dec 2007
Total Posts : 298
   Posted 10/19/2008 8:03 AM (GMT -7)   
Thought I would also throw this out there. I saw it a couple months ago, also in one of my saved search e-mails, and now it seems to have a bit more significance. In case you thought the dairy industry didn't see this coming... I guess they are already considering/expecting the emergence of more information linking MAP and Crohn's.
 
Scenario analysis of changes in consumption of dairy products caused by a hypothetical causal link between Mycobacterium avium subspecies paratuberculosis and Crohn's disease.
 
http://www.ncbi.nlm.nih.gov/pubmed/18650302


July 2007 Drug-Induced Liver Injury
January 2008 Crohn's Ileitis
Currently trying...
Entocort, Enteral Nutrition, Omega-3 (Flax Oil and Fish Oil), VSL#3, Vitamin E


Nanners
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Date Joined Apr 2005
Total Posts : 14995
   Posted 10/19/2008 9:27 AM (GMT -7)   
Illini the MAP theory has been debated on this site a kajillion times. There are so many variables for this to be the only cause of Crohns. There are 32 different genes that have been found to cause Crohns. I also think there are too many triggers. I just don't buy into this MAP theory. I drank milk alot until I was in my mid 30's and stopped because I became lactose intolerant. I had allergies as a child and used antibiotics alot. My kids drank alot of milk and none of them have Crohns. I also smoked for 29 years. So as you can see there are too many variables to believe that one thing caused Crohns. JMHO
Been living with Crohn's Disease for 32 years.  Currently on Asacol, Prilosec 60 mg, Estrace, Prinivil, Diltiazem, Percoset prn for pain and Calcium.  Resections in 2002 and 2005.  Recently diagnosed with Fibromyalgia and doing tests to see if I have Inflammatory Arthritis or AS.


MMMNAVY
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Date Joined Jul 2006
Total Posts : 6927
   Posted 10/19/2008 11:29 AM (GMT -7)   
kajillion...LOL
we have definately covered MAP here, but I think coming from a large ag school that has a vet school there is some interesting differences on the ulcers caused by crohns and those caused by JD in cattle.


Forum Co-moderator - Crohn's Disease
...I will find a way, or make one. -Philip Sidney 1554-1586
Make sure your suffering has meaning...
All suggestions/options/opinions are caveated with please consult with your local health care provider...

Post Edited (MMMNAVY) : 10/19/2008 1:57:17 PM (GMT-6)


Illini
Regular Member


Date Joined Dec 2007
Total Posts : 298
   Posted 10/19/2008 2:34 PM (GMT -7)   
Just trying to share information...I am not trying to be controversial. I am sorry if you are offended, that is not my intention.

You should be able to tell from my post ("...MAP plays a role in some cases...") that I do not believe MAP is the primary cause of Crohn's, nor am I suggesting that.

But it is clear that science and the dairy industry are taking dietary MAP seriously as a possible contributing factor to Crohn's disease.
July 2007 Drug-Induced Liver Injury
January 2008 Crohn's Ileitis
Currently trying...
Entocort, Enteral Nutrition, Omega-3 (Flax Oil and Fish Oil), VSL#3, Vitamin E


MMMNAVY
Veteran Member


Date Joined Jul 2006
Total Posts : 6927
   Posted 10/19/2008 2:40 PM (GMT -7)   
No worries. I know they are really stuggling with this.
Forum Co-moderator - Crohn's Disease
...I will find a way, or make one. -Philip Sidney 1554-1586
Make sure your suffering has meaning...
All suggestions/options/opinions are caveated with please consult with your local health care provider...


Roni
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Date Joined May 2003
Total Posts : 2480
   Posted 10/19/2008 5:41 PM (GMT -7)   
Nanners said...
Illini the MAP theory has been debated on this site a kajillion times. There are so many variables for this to be the only cause of Crohns. There are 32 different genes that have been found to cause Crohns. I also think there are too many triggers. I just don't buy into this MAP theory. I drank milk alot until I was in my mid 30's and stopped because I became lactose intolerant. I had allergies as a child and used antibiotics alot. My kids drank alot of milk and none of them have Crohns. I also smoked for 29 years. So as you can see there are too many variables to believe that one thing caused Crohns. JMHO

nanners, I didn't read anything in illini's post that said that MAP is the only cause of CD.  Illini is simply providing new info about the MAP theory.
 
Also, just because ppl have the genes for CD, doesn't mean they're going to get CD, it just means they CAN get CD. Something has to trigger the disease. Obviously MAP is a worthwhile theory according to doctors and scientists, which is why they continue to explore it.
 
MAP isn't found in every batch of milk. And perhaps at some times in your life your intestinal flora, digestive enzymes, etc. kept from becoming infrected with MAP (if CD can be triggered by MAP). Also, it can take years for MAP to reproduce enough to cause johnes in cattle, so even if MAP could infect ppl, it doesn't mean they would get sick right away.
 
I for one, like the research doctors and scientists, refuse to be closed minded about any theory until it is proven to be inaccurate.

EMom
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Date Joined Aug 2007
Total Posts : 990
   Posted 10/19/2008 6:13 PM (GMT -7)   
Thank you for posting that, Illini!!! I do like to follow MAP because I believe it may be one of the culprits--not necessarily the *only* one, but one nonetheless. Thanks again!
Mom to 16 year old son diagnosed in June, 2007.
Omega 3s, digestive enzymes, probiotics, vit. C, calcium w/D3, a good multivitamin and SCD legal yogurt
Started The Maker's Diet in Sept. '07. Gradually learning/using more SCD recipes, too! (cooking challenged)


Osprey101
Regular Member


Date Joined Apr 2008
Total Posts : 227
   Posted 10/19/2008 11:23 PM (GMT -7)   
MAP is *a* culprit, but probably not the only one, as EMom notes. However, there are problems explaining why the Selby protocol can be used to induce remission in ~95% of patients with three antibiotics with high anti-mycobacterial properties. (It also explains why some 85% of those patients have their disease come back within a year or two- the MAP isn't gone.)

However, I have received a big wad of papers from the UK that I believe make a very good case for the disease being caused- in at least some people- by Klebsiella pneumoniae. There's 10 papers I was sent, and they have a vast number of references and some excellent observations that I am still wading through. However, the one capper- for me- is that the recommendation to control Kp infection in the gut is to cut out the starch- which is the heart and soul of the Specific Carbohydrate Diet, and a tangent of the "Life Without Bread" diet (which simply cuts ALL carbohydrates to 72 grams/day, and reportedly works about 85% of the time in Crohn's).

In short, we now have a very good set of explanations as to what goes on in terms of starch for those that claim the SCD works. Moreover, there's a good tie-in with MAP; although not mentioned in the papers, MAP might get a toehold in a colon that has been badly damaged by Kp infection, one in which the bacterial flora have become so messed up that "anything goes." Whereas a good set of symbiotic bacteria might typically combat MAP, the flora have changed so much that the environment allows MAP to colonize- although not to thrive quite so badly as it does in ruminants.

I have a lot of information to digest. (Ha! Punny!) Anyone else who wants to wade through the biochemistry and microbiology of this disease can drop me a line:
_____________________________________
sorry emails belong only in your profile.

Post Edited By Moderator (MMMNAVY) : 10/20/2008 6:55:15 AM (GMT-6)


EMom
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Date Joined Aug 2007
Total Posts : 990
   Posted 10/20/2008 6:30 AM (GMT -7)   
Osprey, I only wish I had the background to "wade through the biochemistry and microbiology" of it all. What was I doing during college.....? confused Please keep us posted on what you learn about Klebsiella pneumoniae but don't hurt yourself digesting it!

I have questions about the genetics of it all. You know, the more I think about it, if researchers have identified 30 some genes responsible for Crohn's, couldn't there be 312 more UNidentified? By that I guess I'm saying maybe looking for the genetic root is not that critical to figuring Crohn's out. Couldn't it go on and on and possibly not provide any truly helpful answers in the end? I mean, did anyone start looking for a gene that causes stomach ulcers? No, a researcher finally found the culprit--h.pylori. I'm not saying there ISN'T and underlying genetic link here for stomach ulcers...just don't know if understanding that link is critical...

And if there are potentially multiple infectious agents responsible for CD, then wouldn't researchers need to identify genetic susceptibility to each and every invader?

Maybe what I'm trying to say here is wouldn't researchers' time be better spent researching the invaders? Or does this all come down to whether one believes CD to be caused by an infectious agent or not?

I'm not trying to be controversial here, either. These are just questions I have! Anyone else feel this way about the search for the genetics behind it all? Not sure I explained myself very well...my head is spinning this morning... turn... i need my second cup of coffee...
Mom to 16 year old son diagnosed in June, 2007.
Omega 3s, digestive enzymes, probiotics, vit. C, calcium w/D3, a good multivitamin and SCD legal yogurt
Started The Maker's Diet in Sept. '07. Gradually learning/using more SCD recipes, too! (cooking challenged)


Nanners
Elite Member


Date Joined Apr 2005
Total Posts : 14995
   Posted 10/20/2008 7:11 AM (GMT -7)   
Illini I am sorry if I came across a little harsh, I didn't mean for it to sound like that. Its just that this subject has been debated so many times. My personal opinion is, I just think there are too many variables with this disease for MAP to be the cause. It might be a trigger for some, but not all. I personally think my trigger might have been all the antibiotics I was given as a child. I had a doctor who believed in getting it into your system fast, so I used to get shots alot. It could have also been from my starting smoking at an early age (13), I was diagnosed 5 years later.

Once again I apologize if I offended you, it was not entended.

Hugs,
Gail *Nanners*
Been living with Crohn's Disease for 32 years.  Currently on Asacol, Prilosec 60 mg, Estrace, Prinivil, Diltiazem, Percoset prn for pain and Calcium.  Resections in 2002 and 2005.  Recently diagnosed with Fibromyalgia and doing tests to see if I have Inflammatory Arthritis or AS.


Roni
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Date Joined May 2003
Total Posts : 2480
   Posted 10/20/2008 7:16 AM (GMT -7)   

This illness seems so complicated. Like why do some women when pregnant go into remission and others don't? I'm pregnant, and not in remission, although I am a little better than before. So obviously hormones may play a part in this disease too, as well as genetic, and something environmental.

I wish someone would figure out this illness so I can eat McCain chocolate cake again. I can actually tolerate better a little more variety of food while pregnant now too, but not to the extent that I can eat frozen processed garbage that tastes really really good! ;-)

But for those of you on a "homemade diet" like MD or SCD, don't you just wish you could pop a frozen dinner in the oven once in a while? I do.

Nanners, I started smoking at age 13, noticed pain in my RLQ at age 14, quit smoking at age 24 hoping CD would get a little better, but unfortunately it didn't for me.


Osprey101
Regular Member


Date Joined Apr 2008
Total Posts : 227
   Posted 10/20/2008 1:58 PM (GMT -7)   
I don't miss those foods at all, because if there's such a thing as aversion therapy, it's Crohn's- at least for me. The results of eating poorly are just too painful for me to even think about it.

EMom> Interesting note about the array of genes linked to Crohn's. There may be many genes linked to the disorder, but it's clear there's no one "on/off" switch that is found all on its own, with something like a 90% correlation with the disease. Instead, I suspect that the different genes present an array of severity- if genes X, Y, and Z are all positive, let's say, the person has very severe Crohn's. But if genes X and Y are positive, but not Z, the person has a milder form of Crohn's. Now look at that array for 32 genes (known), and it can be very complex, and explain a lot about the severity of symptoms that we see.

Most interesting are those genes that stand for bacterial resistance, of course; if this is a bug-mediated disease, one would expect reduced resistance to invaders. (Presumably this is how Prochymal works- "alien" genes that allow the body to mount an appropriate response to the disorder.) Some of these undoubtedly code for other aspects of the host's biochemistry, and are presumably related to inflammation, or responding to the proteins generated by infectious agents.

As for dealing with multiple infectious agents- I'd take a step back and ask what caused the gut to be so good at harboring all those agents? A more holistic approach, inquiring as to what went wrong to start this whole chain of events, may be more revealing. We can treat and treat and treat with drugs, but if the underlying condition remains in place without correction, the disease will recur and the patient will fail to improve- which is precisely what we see with the Selby protocol.

EMom
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Date Joined Aug 2007
Total Posts : 990
   Posted 10/20/2008 3:03 PM (GMT -7)   
Roni said...
I wish someone would figure out this illness so I can eat McCain chocolate cake again.

But for those of you on a "homemade diet" like MD or SCD, don't you just wish you could pop a frozen dinner in the oven once in a while? I do.


Roni, what is McCain chocolate cake? Sounds political! (kidding).... and YES!, I often wish I could pop a frozen dinner in the oven!!! I am trying to freeze some leftovers more often so they can be taken out and used as "fast food", but that takes planning. Sometimes I just don't want to plan... We used to have a pizza night once in a while, too. Haven't had one of those in nearly a year and a half now. Oh well, change can be good, and in our case it was!
Mom to 16 year old son diagnosed in June, 2007.
Omega 3s, digestive enzymes, probiotics, vit. C, calcium w/D3, a good multivitamin and SCD legal yogurt
Started The Maker's Diet in Sept. '07. Gradually learning/using more SCD recipes, too! (cooking challenged)


EMom
Veteran Member


Date Joined Aug 2007
Total Posts : 990
   Posted 10/20/2008 3:15 PM (GMT -7)   
Osprey101 said...
As for dealing with multiple infectious agents- I'd take a step back and ask what caused the gut to be so good at harboring all those agents? A more holistic approach, inquiring as to what went wrong to start this whole chain of events, may be more revealing. We can treat and treat and treat with drugs, but if the underlying condition remains in place without correction, the disease will recur and the patient will fail to improve- which is precisely what we see with the Selby protocol.


Who is Selby, again? I keep meaning to look him up so I know what you're talking about!

I agree with what you said about a more holistic approach...what went wrong in the first place. It's kinda what I was getting at in my earlier post--that I wish they'd figure out more about the infectious agents and upset of gut flora rather than spending so much research time on figuring out the genetics. How is understanding the genetics of it all really going to help in the end? (I truly don't know here...maybe there's good reason and I'm just not seeing it!)
Mom to 16 year old son diagnosed in June, 2007.
Omega 3s, digestive enzymes, probiotics, vit. C, calcium w/D3, a good multivitamin and SCD legal yogurt
Started The Maker's Diet in Sept. '07. Gradually learning/using more SCD recipes, too! (cooking challenged)


Keeper
Veteran Member


Date Joined Jun 2008
Total Posts : 1058
   Posted 10/20/2008 3:53 PM (GMT -7)   
My current idea about Crohn's is that it results from the loss of the community of beneficial bacteria that we begin life with. There are a large number of bacteria that have demonstrated benefits for Crohn's and there is mounting evidence that once that community is broken up, it is very hard to re-establish it. The non-beneficials occupy the sites and eat the food that the beneficials used to use, so it takes a lot of work to get rid of the non-beneficials and replace them with the good guys. There is the added problem that for the bacterial community to work, you need to introduce the full range of mutually supporting bacteria before they can establish a new normal population. The bacteria in the gut all produce substances that modify the gut immune system and there are more bacteria cells in the gut than there are cells in the rest of your body combined. This gut bacteria community has been called an additional organ in your immune system because it can prevent invaders from getting established and even kill them off with their own antibiotic secretions. Unfortunately, very little is known about what constitutes a beneficial bacterial community that is self-sustaining and even less is known about restoring gut bacteria to such a community. A damaged gut bacteria ecology would also explain why Crohn's will recur after antibiotic treatments.

Osprey101
Regular Member


Date Joined Apr 2008
Total Posts : 227
   Posted 10/20/2008 4:04 PM (GMT -7)   
More stuff on Selby is here:

http://www.crohnscanada.org/Selby.htm

There are people who swear that his antibiotic protocols "cured" their Crohn's. They are in the minority; most were in remission, and their disease came back. I suspect if they'd knocked it back with drugs and stuck to a low-carb diet, more of them would have stayed in remission.
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