Genes + Virus + Timing = CRAP!!: Crohns Disease and Noroviruses

Posted by ERV on August 16, 2010
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Thanks to BleachGate, this is probably the first time many of you all in the Skeptical Community have heard about Crohns Disease (SPOILER: kid with Chrons gets booted from a ‘support’ forum for speaking out against woo-’treatments’).

Crohns is an inflammatory bowl disease (IBD), where your guts do fun things like shrink until your bowls are obstructed, or your body decides you need more passages out of your intestines (Google ‘fistula’. I dare you.), and some times you just good-old-fashioned poop blood. So, dont confuse IBD with IBS, and dont get me started on IBS.

Crohns is the usual grab-bag of ‘What causes this disease?’ Yeah, there are genes that have been associated with Crohns– about 30. But just because you have the genes, or any particular collection of genes, doesnt mean you are going to get Crohns. Some people have correlated Crohns with diet, or smoking, or oral contraceptives, or E. coli… We just dunno what causes this disease yet.

Well a friggen NEATO paper came out that might help treat Crohns, but definitely helps illustrate how complex this stuff is:

Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine.

They have a mouse model that has one of the ‘Crohns susceptible’ genes. That mouse does not develop mouse Crohns on its own.

BUT!

When that mutant mouse is infected with a mouse norovirus, the mouse gets mouse Crohns!

BUT!

You have to infect the mutant mouse at just the right time (virus, then induce some inflammation) for it to get mouse Crohns. If you induce inflammation and infect at the same time, the mouse is fine.

BUT!

If you infect that mouse with a different kind of mouse norovirus, its fine. Timing doesnt matter.

Oh… and intestinal bacteria have a hand in this too (if you give the mice antibiotics, the pathology isnt so bad).

So you have to have 1) the ‘right’ genes, with 2) the ‘right’ virus, at 3) the ‘right’ time, with 4) the ‘right’ commensals for this mouse to develop a pathology similar to human Crohns Disease.

Not everything is as simple as “Disease X is caused by a mutation in Gene X”, or “Disease Y is caused by infection with Pathogen Y”. Sometimes, disease is just an awful, awful slot machine.

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Comments

  1. #1 Jason
    August 16, 2010

    This is VERY cool – I’m totally digging this.

    My question is, this is still considered an autoimmune disease, yes? So once it’s triggered, it’s a chronic condition (like ankylosing spondylitis, and likely, a great many other autoimmune diseases), yes?

    Also, what’s up with not liking IBS? I was reduced to rice and anti-anxiety meds before my oral exams (this is NOT a recipe for success if you enjoy powerlifting) because the anxiety caused nastiness for me. Would you just say my gut went to shit – heh – because of anxiety? Would you not say that this would not be irritable bowel? I don’t know, I didn’t flinch when my docs here said it and chalked it up to my anxiety before my oral exams.

  2. #2 biopunk
    August 16, 2010

    Cool. Thanks for the info.

    And helping spread the word about Rhys and CD. :D

  3. #3 ERV
    August 16, 2010

    Jason– Absolutely psychology has an impact on physiology (and vice versa). I would say gastrointestinal distress caused by obvious anxiety isnt IBS… its gastrointestinal distress caused by anxiety… but Im not an MD…

    My thing is, I have numerous family/friends with Celiac and ulcerative colitis (including a friend who almost died from UC). Some people glamorize these diseases by fawning over their IBS or making a scene ordering at a restaurant because theyre on a lactose-free gluten-free diet to lose weight, trivializing very real, embarrassing, deadly diseases.

  4. #4 Jason
    August 16, 2010

    I definitely see what you’re getting at — what I think it interesting though is that, from my prospective, I just make a big distinction between IBD and IBS. IBS >>> IBD because things like UC and Chrons just suck SO. MUCH. MORE. compared to some lactose intolerance and some unfortunate physical manifestations of stress. OTOH, I don’t know what distinguishes IBS from “gastointestinal distress caused by anxiety” because stress can irritate the bowel, for lack of a better description? I don’t know – same deal – I’m not a MD, void where prohibited…

    A friend of mine with Chron’s (who is new MD) once told me he’d rather have UC than Chron’s because he’d just opt to have the cholostomy and get it over with. But Chron’s can occur anywhere from the mouth the rectum. That… just blows. What a conversation to have, huh? It’s like choosing which cancer you’d rather get.

    But I think I understand what’s up a bit more, now, from your perspective. As always, very cool post.

  5. #5 tim
    August 17, 2010

    Can’t find the paper now, but earlier this year researcher found that if you raise mice free of any intestinal bacteria, you have to infect with one specific bacteria to induce inflammatory bowel disease. IBD may be a final common expression of immune dysfunction, triggered by a variety of things.

  6. #6 ERV
    August 17, 2010

    HAHA! Poor medical correspondent on the Today show has my back: Timely example

  7. #7 darius
    August 17, 2010

    Jason:

    In IBS, the “I” stands for “Irritable”, not “Irritated”. So one answer to your question is that the irritability is the condition, and your bowels being irritated under one particular set of circumstances is irrelevant.

    Another, more snarky, answer is to point out that you may have acquired some deficiencies in your immune system because of long-term stress, but that does not mean you have AIDS.

  8. #8 Rhology
    August 17, 2010

    That is very interesting. My wife is not Cæliac, but is gluten-sensitive/intolerant. Means we have to live the Cæliac life for all intents and purposes.

    I thought I had IBS but adding lots of beans to my diet has pretty much fixed me up.

  9. #9 Tommykey
    August 17, 2010

    I thought I had IBS but adding lots of beans to my diet has pretty much fixed me up.

    Sorry Rho, I just couldn’t help it!

    http://www.youtube.com/watch?v=68v4g6ZjNlw

  10. #10 W. Kevin Vicklund
    August 17, 2010

    I thought I had IBS but adding lots of beans to my diet has pretty much fixed me up.

    Ah, that explains Rho – it’s all coming out the other end.

  11. #11 Rhology
    August 17, 2010

    Hahaha, I knew y’all couldn’t resist the cheap playground taunting. You rival the Westboro

  12. #12 Rhology
    August 17, 2010

    Oops…

    Hahaha, I knew y’all couldn’t resist the cheap playground taunting. You rival the Westboro Babdists in your ability to issue irrational unprovoked insults.

  13. #13 Tommykey
    August 17, 2010

    Y’all? One person, W. Kevin Vicklund, hardly constitutes “y’all” engaging in cheap playground taunting.

    And as for my poking fun with the Blazing Saddles clip, I would have done it to anybody here who wrote about adding beans to their diet. It just so happens that it was written by you.

  14. #14 Rhology
    August 17, 2010

    The “y’all” was in reference to the many times I’ve been here before + WKV now. Just a PSA, as if anyone cares.
    But you’re right, I was not specific enough, sorry about that.

  15. #15 Tommykey
    August 17, 2010

    Apology accepted.

    Plus, I’m sure you remember that on a number of occasions I have chided other commenters who addressed you in needlessly vulgar and vitriolic terms. Something about having principles. :-)

  16. #16 W. Kevin Vicklund
    August 17, 2010

    I’ll be honest – if it had been someone else, I might not have hit the send button. But I still would have thought it, as evidenced by the fact that I thought it before I scrolled down the page to see who wrote it.

    Consider it a light-hearted jest. That’s the way I would have taken it. I’ve even pre-emptively made a similar joke about myself.

  17. #17 Tommykey
    August 17, 2010

    And the Blazing Saddles Youtube clip I linked too turned out not to have sound!

  18. #18 W. Kevin Vicklund
    August 17, 2010

    A thought – imagine what would happen if Rho found AtBC? My joke is mild compared to the banter among friends there.

  19. #19 Sally
    August 17, 2010

    Hi. Very interesting, thanks.
    I recently read some studies regarding Vitamin D (deficiency) and Crohn’s Disease, as well as with gut flora that may be helpful.
    http://www.physorg.com/news197731732.html

    Vitamindcouncil.org
    may be helpful as well.

  20. #20 Rhology
    August 18, 2010

    TK #15,
    Quite true, you have.

    TK #17,
    True, so I made the mistake of trying another one. Funny, but for some reason it made my stomach turn a bit, haha.

  21. #21 thomasbernhard
    August 23, 2010

    I remember hearing Sulfasalazine can effectively treat some Crohn’s patients.

    This drug also completely reversed advanced cirrhosis in end-stage alcoholic mice.