Maybe I need more evolutionary medicine…

| 18 Comments

Miss me, anyone?

I'm in the hospital with my worst-ever flare-up of Crohn's disease. I promise to spare you the disgusting details, but it has been bad enough to keep me away from an Internet connection for almost a week. That should tell you something.

But I did learn about some preliminary research that indicates that perhaps my condition results from changing the environmental conditions away from the usual coevolutionary relationship between humans and intestinal parasites. A small clinical trial tested the effect of giving Crohn's and ulcerative colitis patients porcine whipworm, Trichuris suis, and got some intriguing results. The researchers note that the initial study is too small to separate possible placebo effects, but positive responses in several patients indicate the need for a larger controlled study.

The basic gist behind this is that the porcine whipworm parasites are invasive enough to obtain an appropriate response from the gut, while being out-of-place enough in the human system that they don't pose a significant health risk of their own. The researchers also note an observed inverse relationship between incidence of Crohn's and colitis cases and prevalence of intestinal parasitic infections. If this works out, continuing maintenance of Crohn's and ulcerative colitis in at least some patients may include a routine of ingesting porcine whipworm eggs periodically. While I usually shudder at the idea of deliberate nematode ingestion, my recent experiences certainly put me in favor of giving it a try.

18 Comments

When I was doing my Ph.D. in microbiology, I was studying superantigenic toxins, which act by stimulating T-cells in a relatively non-specific way (based on a part of the T-cell receptor called the V-beta). I had identified a couple of these toxins, purified them, and done some expts to examine their biology. One of the things we did was look at the V-beta profile of human T-cells stimulated with the toxins. Once this was done, we looked in the literature to see if any diseases of unknown etiology were marked by similar “V-beta skewing”. The point (finally) is that Crohn’s disease is marked by skewing of the T-cell population similar to what our toxins produced. Not proof, by any means, but S. aureus (the organism that produces these toxins) is a common cause of food poisoning, and these toxins are tough, and could easily survive the GI tract and cross the intestinal lumen into the gut wall M-cells (immune cells of the gut wall, IIRC). Long story short, the worm approach might work because intestinal worms down-regulate certain parts of the immune system, diverting resources to humoral rather than cellular immunity. Other immunomodulatory therapy approaches might also be useful. Similar interesting interactions between parasitic worm infections and HIV have also been noted. Good luck with your therapies.

Glad to see you’re online Wes. Now you’re at least partially in your natural habitat. We’re pulling for you!

Wes-

You were most certainly missed and we’re all wishing you a full and speedy recovery. Without you, Bill Dembski has no stalker. :)

Hi Wes - great to have you back. That’s an interesting story with the nematodes, and it nicely parallels recent studies about the spike in the prevalence of allergic diseases in developed countries. In that case, there is increasing evidence that chronic exposure to bacteria, especially early in life, may have a protective effect against allergies. [Incidentally, one of the best sources of protective bacterial products seems to be cow manure - swallowing nematodes may not be that bad, after all! ;-) ]

So, as you said, our immune system has developed in a close co-evolutionary relationship with our pathogens, and our increasingly microbe- and parasite-free existence seems therefore to alter its balance towards hyper- and self-reactivity, leading to allergies and autoimmune (eg, Chron’s) diseases.

Idle lymphocytes are the devil’s tools, I guess.

Hang in there. A

Burrill Crohn’s disease!

Let’s hope you don’t need to have anything excised. If Crohn’s is a problem, short bowel is too.

And thanks for the posts about the worms / Wurms / Vermes. I had heard about them but it is cernainly nice to have a short explanatory note: that is the mortar that holds the brick in (mental) place.

Incidentally, one of the best sources of protective bacterial products seems to be cow manure

Keeping up with Dembski’s prolific writing may be the best thing for you, Wes. Feel better.

In all seriousness, stay away from the cow manure - a substantial portion of the cattle in the U.S. are silent carriers/shedders of E. coli O157:H7, which can be fatal. An interesting case of evolutionary biology btw, since it’s asymptomatic in cattle, while being nasty to humans who get it (largely from undercooked contaminated ground beef).

Maybe you want to look at this: http://www.newscientist.com/news/ne[…]d=ns99994852

It’s a novel therapy for Crohn’s and/or similar.

Frank, it actually is low chronic exposure to endotoxin from E. coli and other bacteria that seems to shift immune reactivity away from allergy-provoking to protective (Th2 to Th1, for those in the know). I guess the key words here are “low” and “chronic”, as opposed to acute infection. No one is advocating raw manure meals here!

I guess the key words here are “low” and “chronic”

… and O157:H7!

Interesting, though, that it’s the nematodes that are supposed to provoke a Th2 response (and against which a Th2 response is supposed to be effective). Could it be that Crohn’s involves too high a Th1/Th2 ratio, rather than the reverse? I think I may have my next journal club topic.

Russel: with the important caveat that any model that only takes into account Th1/Th2 polarization as the driving mechanism of immune response regulation is hopelessly inadequate, yes, indeed, pro-inflammatory cytokines produced by Th1 T cells have been shown to be involved in several autoimmune manifestations (eg, diabetes).

I think the message here is however not that Th1 and Th2 balance is the key to understand these immune pathologies, but rather that a healthy immune system depends on a dynamic balance between activation and suppression of its various components. Like most organ systems, the immune system needs “exercise”, and by over-sterilizing our environment we are depriving it of necessary stimuli. There was a good review about the hygiene hypothesis in Science a year or so ago. I can try to look for it if you’d like me to.

April 1 came late this year in my neighborhood. I’ve just finished reading your post on Stephan and the allosaur, both here and way out there on Mars of all things. Continents do drift.

I write to tell you three things. First, it is nice to see your note and that you are back in circulation, more or less. Second, thanks for telling me about the disease and treatment. There is something about ingesting those eggs though.… Finally, take care of yourself. I wish you the best and send good energy your way.

From Eurekalert:

Researchers at the University of Toronto have isolated a gene that predisposes people to Crohn’s disease.

“Isolating this gene is a critical step towards improved diagnosis of this disease and developing better therapies for Crohn’s sufferers,” says Katherine Siminovitch, a U of T professor with the Department of Medicine … “There’s an urgent need for better treatment for patients with Crohn’s.”

[snip]

Using DNA samples from family groups, Siminovitch and her research team employed a technique called positional cloning to first locate the chromosome containing the gene and then identify the gene. Their findings appear online April 11 in Nature Genetics

[snip]

The gene isolated by the researchers produces a protein that sits on the cell surface and regulates how substances enter and exit the cell. In a majority of Crohn’s disease patients, this protein functions improperly and allows toxins easier access to the cell.

Welcome back Wes. I was getting worried.

Wes, so sorry to hear about your hospitalization. Get well soon.

As far as the nematodes are concerned, this was mentioned in a great book by Carl Zimmer called _Parasite Rex._ I was shocked when I read it, but it seems plausible. In the book, he talked about how early results for the cestode ingestion (I think he was using a tapeworm as the therapy, and not a nematode) were promising.

BCH

Dear Wes Sorry to hear about your funny tummy. Crohn’s is probably a disease of civilisation. Most common chronic diseases of modern sopohisticated cultures are rare or absent in hunter-gatherers who are our best surrogate for Paleolithic man. The Paleolithic diet is a distinct scientific discipline and researchers in it are identifying molecular mechanisms responsible for these diseases. Unfortunately we don’t have any case series or controlled trials as yet. For more information see www.paleodiet.com (the first link is to some stuff I wrote which someone posted up for me), or www.thepaleodiet.com .

The actual philosophical issue at stake is that changes in diet can affect phenotype as much or more than changes in genes can. Read that 3 times. Once you accept that then you can loosen the shackles of looking for Crohns genes and get on with the real work of finding which dietary factors have caused it. Do not confuse phenotype with genotype.

Unfortunately what can be done cannot always be undone (those memory T-cells can be pesky), but understnading why things happen certainly helps us undertand how to prevent it in others.

Cheers Ben

About this Entry

This page contains a single entry by Wesley R. Elsberry published on April 9, 2004 8:18 PM.

Squid Hox genes was the previous entry in this blog.

Are “intelligent agents” supernatural? is the next entry in this blog.

Find recent content on the main index or look in the archives to find all content.

Categories

Archives

Author Archives

Powered by Movable Type 4.381

Site Meter