Some Random Thoughts About Inflammatory Bowel Diseases

[tex]

Hi All,

In the interest of gaining some insight into the "How, What, Where, and Why" of Inflammatory Bowel Diseases, (IBDs), I've been sort of collecting my thoughts, lately, and here are some of the things that I believe to be true:

We often wonder if this group of diseases is actually an autoimmune issue, as is widely upheld by the majority of the medical community, or if viruses, bacterial overgrowth, or some other mechanism, might be implicated, instead. With the following observation as a background:

Crohn’s disease is common in highly industrialized Western countries where helminths, (a certain variety of intestinal worms), are rare, and uncommon in less developed areas of the world, where most people carry worms.

If we look at the results of trials using helminths, (pig whipworms), as treatment, for example, in a cohort of Crohn's patients, we see that in some trials, the response rate approaches 80%, with the remission rate exceeding 70%. I don't see how that would be possible, unless the disease were an autoimmune issue, so I believe that IBDs are almost certainly driven by autoimmune responses, particularly since I'm not aware of any evidence that would conclusively contradict this theory.

http://www.ovamed.org/all/clinicalstudi ... 202005.pdf

To confuse the issue, though, in this trial with Ulcerative Colitis, (UC), patients, only a little over 40% of the patients were helped.

http://www.ovamed.org/english/clinicals ... ers_UC.pdf

Of course, the big question is, "how did the body's immune system become corrupted in the first place?". I still believe, (as I have for some time now), that a virus of some type is responsible for altering the genes which predispose the body to susceptibility to autoimmune issues. As far as I can discover, bacteria cannot alter genes, but of course, altering genes is one of the primary functions of viruses. Obviously, this doesn't imply that a bacterial imbalance in the gut cannot cause GI distress, including diarrhea, and various other symptoms, {in particular, the chronic condition known as Irritable Bowel Syndrome, (IBS)}, nor does it rule out the possibility that bacteria may act as a trigger, in some cases, to activate the genes, and subsequently trigger an IBD, but I don't think the odds are very high that it will someday be shown to be the defining mechanism which results in any of the IBDs, (though it may be one of many possible triggers).

Since this is strictly my opinion, I'm sure this post will bring some thought-provoking contrary opinions, but that's great - that's how we learn new things.

Tex

[harvest_table]

Of course, the big question is, "how did the body's immune system become corrupted in the first place?". I still believe, (as I have for some time now), that a virus of some type is responsible for altering the genes which predispose the body to susceptibility to autoimmune issues.

The hygiene theory comes to mind. I'm a first born.

http://www.wjgnet.com/1007-9327/14/165.asp


Also have come across a number of "conversations", but nothing in pubmed which states these worms are protective against a virus attack.

Weinstock: Most people don't carry them; you can tell if people have helminths. But not everybody without helminths will get an immunological disease. Luck, genetics, and certain other triggers must be present for the disease to emerge. But if you have helminths, we believe that you will be less likely to get IBD because you have protective factors. A virus, for example, is less likely to trigger the disease in someone with helminths.

Here's everything you wanted to know about worms..
http://64.233.167.104/search?q=cache:L4 ... cd=7&gl=us

IBD's are multifaceted for sure. Have we so quickly become a clean society and also, as quickly start eating foods so far from our roots?

Joanna

[tex]

Hi Joanna,

Thanks for the links. While I am also a firstborn, the hygene theory did not work at all for me. The first house I lived in did not even have running water, let alone running hot water. There was no plumbing at all in the house - my parents carried water from a well, in an open bucket. For the first eleven years of my life, the toilet was various outhouses. I lived on a farm, with animals of all sizes. I played in the dirt, and went barefoot, (in the summer), for years. I remember drinking water from small "springs" along creek banks, when I would get thirsty, while out prowling about.

I also remember being "wormed", but I don't recall the exact age - I was probably about four or five, but that's just a guess, I might have been younger. I do remember seeing at least one large worm as a result of the process, presumably an ascaris lumbricoidesm, (roundworm).

Nevertheless, by the time I reached the age of six or seven, I had serious problems with asthma. About 20 years later, hay fever came along, and then, later in life, food intolerances.

I believe that Weinstock is wrong, in that statement you quoted - he gave a poor example of a trigger. It's not that viruses trigger IBDs - they alter genes. Once the genes are altered, the IBD is triggered by various "external" mechanisms, many of which the helminths are obviously capable of modulating. Frankly, I doubt that helminths have any significant effect on viruses, but they definitely have an affect on many triggers which are capable of initiating an IBD reaction.

IOW, you blame excessive "cleanliness" for your autoimmune issues, but theoretically, I did everything "right", (unknowingly, of course), and lived a relatively "dirty" childhood, but I probably have more autoimmune issues than you. LOL. Just like the conclusions in the reference you cited for the hygene theory, no clearcut correlations can be found - nothing really makes any sense.

Tex

[mle_ii]

There are a great many ways to alter genes and their expression. Virus being one of the many, just off the top of my head I'd say chemicals (heavy metals, pesticides, etc), bacteria (mainly the products of the bacteria not the bacteria themselves), stress, radiation (gama rays, xrays, radio waves, etc). Might be more but I'll stop there.

And also the autoimmune response would be effected even without genetic changes or expression by the things above. Along with a great many other potential causes.

One thing that puzzles me is how low dose naltrexone fits into this. It is used to increase immune response and has been found to help with Crohn's Disease, whereas it hasn't been shown to help with Ulcerative Colitis.

I think that there is something to the cleanliness issue, though it's not the whole picture. I grew up on a farm, ate/drank many unclean things, didn't wash my hands, etc, even had "fun" with intestinal worms (pill worms I believe), yet I had LC.

What's not clear to me is what your theory is. At first it seemed to point to worms, elsewhere you've mentioned genetic and even in this thread you pointed that you dealt with worm issues as did I. Yet we both developed this disease.

Though I will admit I'm all over the place as well. But I'm thinking that it's all part of the bigger picture and that there won't be one smoking gun here.

Mike

[mle_ii]

Hmmm... that last part sounded pretty negative. I don't think that you are "all over the place" but I know I sound like I am. And I'm not poo pooing (ha, no pun intended) what you're saying. Just that I'm unsure of where you are going with this.

[tex]

Mike,

Outside of viruses and spontaneous mutations, chemicals and radiation are the basic mechanisms by which genes are altered. I suppose, though, if they produced the "right" chemical byproducts, (certain acids, for example), bacteria might indeed be able to alter genes, but I'm not sure how commonly that occurs.

I don't agree with the theory that worms cause IBDs - just the opposite, I think they're protective of them, (as per the University of Iowa research). I was merely pointing out that the "excessivly clean" theory has a lot of holes in it. (I was even breast fed, and that didn't work either). Obviously, (if this is indeed an autoimmune disease), something alters the "right" genes, that predisposes us to IBDs, and then something else "triggers" it. I have a hunch that something is a virus, but whatever it is, the initial genetic mutation probably determines the type of IBD that we will be susceptible to.

Theory? What theory? All I can offer is random thoughts. While we seem to know, (or at least think we know), a lot of isolated bits and pieces of information about IBDs, we still have a long, long way to go, before we will ever figure out how it all actually works, so "all over the place" may be an apt description. LOL.

Oh, regarding the naltrexone - it may have an effect similar to the helminths. IOW, by stimulating the immune system in a limited, (controlled), way, it preempts an "unlimited" autoimmune response.

Tex

[mle_ii]

Right, sorry, I didn't think you thought nor do I think worms cause the disease, but can be protective, just as somehow bacteria seem to be protective as well.

Perhaps I'm misunderstanding, but IBD being autoimmune (if it is) doesn't require a genetic change, nor does it require it as a cause. Though as you point out genetics might predispose one to getting IBD or an autoimmune disease. Just like having the genes involved in Celiac Disease doesn't mean you'll get it and on the other side of the coin nor does it mean that if you don't have them that you won't get Celiac Disease.

Actually you just cleared up your theory quite well.

Though I agree that a viral aspect is certainly a likely suspect. Given how viral infections tend to cause immune system problems which indeed IBDs are.

Thanks for your thoughts, makes me think.

Mike

[tex]

Quite true, but cases of celiac sprue, for example, without "proper" genetic "matching" are pretty rare, aren't they? If you look at the compiled results of our gene tests, for example, everyone tested has a pair of gluten sensitive, (or celiac), genes. (Of course, for all I know, everyone in the world might be in the same boat, as far as genes are concerned), so I have no idea if they are really related to MC, or not.

I thought all autoimmune diseases were connected with mutated genes, but maybe I just assumed that.

Tex

[mle_ii]

Quite true, but cases of celiac sprue, for example, without "proper" genetic "matching" are pretty rare, aren't they? If you look at the compiled results of our gene tests, for example, everyone tested has a pair of gluten sensitive, (or celiac), genes. (Of course, for all I know, everyone in the world might be in the same boat, as far as genes are concerned), so I have no idea if they are really related to MC, or not.

I thought all autoimmune diseases were connected with mutated genes, but maybe I just assumed that.

Tex

First, you are correct, the majority of folks with CD do have those 2 genes, but there are folks without them that do. Also, I think I remember reading some statistic for the number of folks of european decent having the CD genes, and the number was rather significant.

It's a very good assumption as I would venture to guess that a significant number of folks with autoimmune disease have a genetic factor that predisposes them to it. But let's look at CD, it's autoimmune, yet it isn't really a mutated gene. And it isn't the gene alone that is the cause. I would even venture to guess, as I've done many times LOL, that this gene was selected for a purpose, perhaps those of european descent survived some bacterial/viral/etc infection that looked a lot like the proteins found in deanimated gluten. I've been keeping an eye on it, but I keep wondering of the rotovirus is that virus. From some studies I've read on it the outer layer of the bacteria has the same key to which the CD genes fit and thus signal the body to fight. I think, and I'm not as sure about this, that even diabetes has had some signifcant factors related to rotovirus. And if not rotovirus perhaps some other one that we survived.

It just so happens that we've modified wheat and other glutenous grains to contain more of this protein and thus we're in the mess we're in now.

Oh and back to autoimmune, one of the other causes would be something that overwhelms the immune system, too much of a bad thing doesn't give the immune system to decide if it's ok to fight or not and it opts for fighting in the case where it is overwhelmed. Most times it's ok, in the cases of autoimmune diseases it's not so good.

Mike

[Polly]

Interesting discussion. A few thoughts:

Mike, I like your gene selection theory. We know this is true in other cases. For example, the sickle cell gene confers some immunity to malaria. And some believe that those with hunter-gatherer genes are better at fighting infectious disease........ the first time I heard this was during a discussion with Dr. Fine.

Don't forget, strictly speaking, MC is not an autoimmune disease. At least not in the initial stage of colitis, where the body begins attacking its good gut bacteria. To be AI the body needs to be attacking its OWN tissues - not "visitors" like bacteria. Of course, based on what we learned recently about how the body gets bacteria at birth and how important this is for future colonic stabilization, perhaps we SHOULD consider our gut bacteria to be our own tissue! lol!

Mike, re modifed wheat.....I read that the wheat our grandparents ate was only 3% gluten. Wheat today is 50% gluten. They have increased its gluten protein fraction because that is what makes baked goods so light and airy. Maybe we have family histories rife with genes for gluten sensitivity, but it would never have become apparent if our ancestors ate such small amounts.

Cheers!

Polly

[tex]

Good point, Polly, (that MC is not an autoimmune disease, at least not initially). That implies that CD is not actually an autoimmune disease, also. (The immune system is actually attacking the gliadins, not the villi of the small intestine). I have to agree that technically this is correct.

However, note that many authorities list celiac sprue, (non-tropical, of course), as an autoimmune disease. One of the best examples of this is seen in the very comprehensive list compiled by the American Autoimmune Related Diseases Association:

http://www.aarda.org/research_display.php?ID=47

Note also, that they list Crohn's and UC, but not any other IBDs, while other sites offer other "views":

Autoimmune Inflammatory bowel disease--The general name for diseases that cause inflammation in the intestine, the most common of which are ulcerative colitis and Crohn's disease.

http://www.cidpusa.org/disease.html

Here's where it gets interesting. Consider this definition of autoimmune diseases, from the Johns Hopkins Medical Institutions's site:

Autoimmunity is present in everyone to some extent. It is usually harmless and probably a universal phenomenon of vertebrate life. However, autoimmunity can be the cause of a broad spectrum of human illnesses, known as autoimmune diseases. This concept of autoimmunity as the cause of human illness is relatively new, and it was not accepted into the mainstream of medical thinking until the 1950s and 1960s. Autoimmune diseases are defined as diseases in which the progression from benign autoimmunity to pathogenic autoimmunity occurs. This progression is determined by both genetic influences and environmental triggers. The concept of autoimmunity as the actual cause of human illness (rather than a consequence or harmless accompaniment) can be used to establish criteria that define a disease as an autoimmune disease.By this approach, Rose and Bona (Immunology Today, 14: 426-430, 1993) have distinguished the evidence for an autoimmune etiology at three different levels: direct, indirect, and circumstantial.

http://autoimmune.pathology.jhmi.edu/whatis_disease.cfm

The direct and indirect levels are described on the site, of course, but let's consider their definition of circumstantial etiology of autoimmune disease:

When direct and indirect evidence to define an autoimmune disease are not available, investigators are left with circumstantial evidence, that is, with listing "markers" descriptive of autoimmune disease. Examples of these markers are:

* positive family history for the same disease, or for other diseases known to be autoimmune
* presence in the same patient of other known autoimmune diseases
* presence of infiltrating mononuclear cells in the affected organ or tissue
* preferential usage of certain MHC class II allele
* high serum levels of IgG autoantibodies
* deposition of antigen-antibody complexes in the affected organ or tissue
* improvement of symptoms with the use of immunosuppressive drugs (such as corticosteroids)

If that doesn't cover MC, I'm a monkey's uncle. LOL.

I get a vague feeling of déjà vu about this topic, but I always find it very interesting.

Anyway, to get to my point, maybe the definition of AI diseases should be changed. After all, apparently, the gut flora population balance never significantly changes during our lifetimes, (unless altered by antibiotics, of some similar "insult", of course). If those little buggers are an internal, "integral", necessary, "component" of our body ,then why should they be arbitrarily classified as "foreign".

I suggest that if our immune system chooses to attack a "component" of our body that is essential to our well-being, then it is, in essence, attacking it's "own" tissues, since the tissue that it is attacking is there for a purpose necessary to it's own good health. The current definition is simply another case of an arbitrary definition that serves to confuse the issue, much like the arbritary definition of the essential diagnostic criteria for celiac disease does a grave injustice to most patients with gluten-sensitive enteropathy, but in the medical world, most definitions, (once accepted), seem to be "chiseled in stone".

Love,
Tex

[mle_ii]

Hmm... I'm fairly certain that CD is indeed autoimmune, it's not the anti gliadin that's the autoimmune aspect it's the anti TTG, TTG makes up a lot of the parts of the body, it's pretty much the glue that holds us together.

The reason that bacteria that are normally tollerated in the body but end up becoming an foreign invader is either the bacteria changed significantly, the sensory part of the immune system is amiss or finally the bacteria get to places that they normally shouldn't at least in the numbers that cause a problem. This final part, basically leaky gut, is the biggest cause here. Bacteria to a certain degree makes its way into areas it shouldn't but not in numbers where the body feels it's under attach. It's when the gut lining is heavily compromised, by the various mechanisms I've mentioned elsewhere, that this normally normal gut bacteria is seen as a bad thing to have.

The autoimmuneness of disease is actually a normal and good function of the body, it's when it goes beyond it's normal mode that it becomes an issue. Just like oxidation, inflamation, diarrhea, vomiting, etc, and other body processes, when it's out of wack it's bad, when it's normally function it's good.

Mike

[tex]

H

mm... I'm fairly certain that CD is indeed autoimmune, it's not the anti gliadin that's the autoimmune aspect it's the anti TTG, TTG makes up a lot of the parts of the body, it's pretty much the glue that holds us together.

Yes, but when you take away the gluten, the TTG antibodies disappear, don;'t they? IOW, the initial reaction, (and/or the "controlling reaction), is not AI in nature - it's a "sympathetic" effect. Right?

The reason that bacteria that are normally tollerated in the body but end up becoming an foreign invader is either the bacteria changed significantly, the sensory part of the immune system is amiss or finally the bacteria get to places that they normally shouldn't at least in the numbers that cause a problem.

Agreed, but actually it's the immune system response that's most likely to be corrupt, isn't it, (rather than the sensing)?

The autoimmuneness of disease is actually a normal and good function of the body, it's when it goes beyond it's normal mode that it becomes an issue. Just like oxidation, inflamation, diarrhea, vomiting, etc, and other body processes, when it's out of wack it's bad, when it's normally function it's good.

I'm having a problem thinking of an example when an autoimmune response is good, but maybe my judgment is just clouded because of so many unpleasant experiences with it. LOL. While it appears to be true that it's a normal part of our makeup, that doesn't necessarily imply that it's good. (Nor does it imply that it's bad, either).

Tex

[mle_ii]

Yes, but when you take away the gluten, the TTG antibodies disappear, don;'t they? IOW, the initial reaction, (and/or the "controlling reaction), is not AI in nature - it's a "sympathetic" effect. Right?

Well, yes and no. You could make the same argument for any of the other autoimmune diseases. Take away the trigger and it goes away.

Agreed, but actually it's the immune system response that's most likely to be corrupt, isn't it, (rather than the sensing)?

I'm talking about the ... ugg, can't remember the actual name... that senses the contents of the gut. Mast cells? Hmm... gotta look that up. So if this part is missing the sensors, or the sensors are too sensitive or have too many immune sensors then the immune system is corrupted. Just like how if your sense of touch is not working right doesn't mean that the rest of your body is out of wack, but hold on to something hot and your body doesn't sense it correct and you get burnt.

I'm having a problem thinking of an example when an autoimmune response is good, but maybe my judgment is just clouded because of so many unpleasant experiences with it. LOL. While it appears to be true that it's a normal part of our makeup, that doesn't necessarily imply that it's good. (Nor does it imply that it's bad, either).

Tex

The process is used for ridding the body of cells that are no longer genetically the same. In other words a virus or something else changes the cell, the body detects that, and then attacks and destroys it. Without this process we'd all have cancer, tumors, viral infections etc. Now virus are good at hiding, and in the case of CD told to attack the wrong thing or too much.

[tex]

The process is used for ridding the body of cells that are no longer genetically the same. In other words a virus or something else changes the cell, the body detects that, and then attacks and destroys it.

You got me there - that's definitely not routine apoptosis, so I sure can't argue with that. LOL.

Tex