Crohn's Disease, the Rise of Agriculture, and Gene Expression

Just read a really complicated article that went way over my head in Discover Magazine, but thought I'd share it as there are some interesting theories presented.

Here's an excerpt:

So what happened? The authors posit that the 503F allele was selectively favored at some point in the past, and flanking it were the Crohn’s disease risk elevating variants of IRF1 and IL5. All things equal it is best not to have a risk for this disease, but all things are not equal. If there was a strong enough selective pressure on the target, 503F, then the downsides of the fact that it came as a “total package” with some deleterious alleles would be irrelevant. Over a long enough evolutionary time the deleterious alleles would be purified through negative selection because recombination does break apart associations, but there’s a lot of reality which consists of being between beginnings and ends.

Basically, the idea is that agriculture put a selective pressure on the genome that brought along genes that increased risk of Crohn's disease. To put that in more plain words, the rapid change in environment caused by the rise of agriculture (e.g. living off of certain grains), put pressure on the natural selection of genes. Certain gene variants (mutations) were favored in the new environment and so flourished. Unfortunately, those positive gene variants (which helped humans deal with the benefits of agriculture) brought with them negative gene variants (which increased risk of disease).

Interesting theory. The writer that's critiquing the article doesn't completely agree with the conclusion, but definitely some interesting analysis.

Been a while since I posted ...

It's been quite a while since I've posted anything up here. I moved, started a new job, wife had a baby, and just generally been swamped. I've been really behind on doing any research on IBD and Crohn's but I'll likely start picking it up again. Appreciate the questions that I've been getting on here over the past couple months. Sorry for not responding to them all.

In other news, I'm coming up on two years on the Specific Carbohydrate Diet. It's been working pretty well so far (but it's time consuming!).

Broccoli Fiber Combats Crohn's Disease

Saw this article in Life Extension magazine about broccoli:

An article published online on August 25, 2010 in the journal Gut reveals that fibers found in broccoli and plantain block a stage in the development of the Crohn's disease, an inflammatory bowel disease. The stage involves a process known as translocation, which is the invasion of microfold cells (M-cells) lining the colon by bacteria, particularly E. Coli, which tend to adhere to one another.

Crohn’s disease is uncommon in countries whose citizens regularly consume fibrous fruits and vegetables, while the incidence of the disease has increased in Japan with the rise of Westernized dietary habits. Additionally, some enteral feeds have been shown to result in clinical remission. “It is therefore a plausible hypothesis that dietary factors may have either harmful or protective roles in Crohn’s pathogenesis as a consequence of their effects on the interaction between the host epithelia and intestinal microbiota,” the authors write.

Dr Barry J. Campbell of the University of Liverpool and his associates tested the effects of soluble fiber from leeks, apples, broccoli and plantain in cultured human M-cells. Concentrations of 5 and 50 milligrams per milliliter plantain fiber, and broccoli fiber concentration of greater than 0.5 milligrams per milliliter helped inhibit E. Coli translocation. While apple and leek failed to show an inhibitory effect, translocation of E. Coli was enhanced by the fat emulsifier polysorbate 80, which is included in some enteral feed solutions administered to Crohn’s disease patients and is a common dietary additive. The results were confirmed in epithelial tissue samples derived from humans who underwent surgery for colon cancer or colonoscopy.

“These studies show that different dietary components may have powerful and contrasting effects on bacterial translocation across intestinal M-cells,” the authors conclude. “These effects may be relevant to the role of environmental factors in the pathogenesis of Crohn’s disease and suggest possible novel therapeutic approaches.”

This is related to an earlier post I had about broccoli. Eat your broccoli!

Caltech Researchers Discover that Gut Bacteria Affect Multiple Sclerosis

I've had a couple blog posts about multiple sclerosis (MS), including links to both viral and bacterial infections. I just came across another study, this one from Caltech, that found that gut bacteria can affect the onset of MS. The researchers found that gut bacteria could influence the creation of Th17 cells (certain kinds of immune helper cells).

The bacteria aren't necessarily the entire cause of the disease, but they may represent the "environmental" component that when combined with genetic susceptibility causes the disease to kick into gear. Here's an excerpt:

Mazmanian and his colleagues don't, however, suggest that gut bacteria are the direct cause of multiple sclerosis, which is known to be genetically linked. Rather, the bacteria may be helping to shape the immune system's inflammatory response, thus creating conditions that could allow the disease to develop. Indeed, multiple sclerosis also has a strong environmental component; identical twins, who possess the same genome and share all of their genes, only have a 25 percent chance of sharing the disease. "We would like to suggest that gut bacteria may be the missing environmental component," he says.

It's amazing that inflammation of something as sterile as the central nervous system and brain could be impacted by what's going on in your gut. But there does indeed seem to be a connection. Hopefully they can find the bacteria (or type of bacteria) that triggers Crohn's Disease as well.

Key proteins that cause Celiac disease discovered

Saw a few articles (ABC News, Geek System) about a study in Melbourne that identified several proteins that cause Celiac Disease. There are apparently three or four different protein fragments that can trigger the disease. Celiac is caused due to an allergic reaction to these proteins. The researchers hope to create an immunotherapy treatment where patients can build up immunity to those proteins. Very interesting development and certainly gives hope for the more than 2 million people in the US that suffer from the disease.

Here's an excerpt about the potential immunotherapy treatment:

Professor Anderson says the findings are being used to develop a new class of drugs, called peptide-based immunotherapy.

This involves injecting patients with a small amount of the toxic peptides to "desensitise" their body to them.

The researchers say the first phase of trials of the therapy to assess safety and tolerability were completed in June, and final results are expected in coming months.

Definitely great news.

Controversial treatment for MS - and another angle for research of IBD

I don't know much about multiple sclerosis, but I see articles about it all the time as I monitor news about autoimmune diseases. I came across an article about a controversial treatment for MS that a person in Britain couldn't get because it hasn't been officially sanctioned by the government yet via clinical trials. For a person with IBD, I found the treatment less interesting than what it suggests about the potential cause of the disease.

Here's a really short excerpt just to give you an idea:

In 2005, Zamboni’s wife Elena was diagnosed with MS and he embarked on a mission to find out everything about it, from poring over medical literature dating back 100 years or more, to using state-of-the-art body-imaging techniques.

His conclusion was that this wasn’t only an autoimmune disease, but also a vascular one, caused by restricted, blocked, malformed or twisted veins in the trunk and neck. A small study showed that 90 per cent of his patients had venous obstruction. He named the condition chronic cerebrospinal venous insufficiency (CCSVI) and went further, postulating that an excess of iron, which causes inflammation and cell death, was responsible for tipping the immune system out of balance, resulting in MS symptoms.

The treatment was to unblock these twisted or malformed veins (similar to an angioplasty). What I found interesting is that an autoimmune disease, in this case MS, might not just be caused by the environment or genetic susceptibility, it might also include a physical malformation in the body that can be reversed! Might there be something similar with IBD? They should add that to the list of things to research.

UPDATE (8/2/2010): Saw an article in the WSJ about a study that refutes the Zamboni theory regarding jugular vein blockage. Jury is still out I suppose.

Why some people with IBD may not respond to corticosteroids

We all know that corticosteroids are one of the first drugs prescribed to deal with IBD. But it doesn't always work for everyone. Why?

I just came across a press release about new research that uncovered why many people with lupus (another autoimmune disease) do not respond to corticosteroids - or at least steroids in high doses. An excerpt that explains why this is the case:

Currently, those with lupus and other autoimmune diseases, commonly treat the condition with corticosteroids to suppress their overactive immune system and prevent it from attacking healthy tissues which can result in symptoms such as inflammation, pain and organ damage.

These steroid treatments work by killing certain immune system cells, including plasmacytoid dendritic cells (PDCs) that overproduce type 1 interferons, an immune system substance that contributes to lupus and other autoimmune diseases. However, unlike other conditions, steroid treatments are not as effective against these cells in those with lupus.

By largely studying children with systemic lupus erythematosus (SLE), BRI scientists in collaboration with scientists at Dynavax in Berkeley, CA, were able to solve the mystery behind the resistance. They determined that two immune system proteins known as toll-receptor 7 (TLR7) and toll-receptor 9 (TLR9), cause an activation of PDCs—the very cells steroids target—negating the effects of treatment. BRI scientists reported their findings in the June issue of the journal Nature.

A similar resistance mechanism might be at play with people with IBD (and other autoimmune diseases). It hasn't been proven yet obviously, but it's certainly something to consider when you're working with your doctor to deal with a serious flare-up. The traditional prednisone or budesonide (Entocort) may not work for you simply because your body works against the mechanism of the drugs.