IBD Less Common in Sunny States

I've blogged about this before, but there was a recent study that revealed that people who live in sunnier regions of the United States are less likely to develop IBD. It confirms previous research conducted in Europe that generated the similar results. The study followed over 200k participants that began the study without symptoms of IBD.

The basic explanation for this is Vitamin D. There's a strong role for Vitamin D in the immune response and IBD patients (including myself) often have low Vitamin D levels. So stop postponing that vacation to Hawaii already!

Here's an excerpt:

"A leading explanation for this north-south gradient in the risk of ulcerative colitis and Crohn's disease may be differences in exposure to sunlight, or UVB radiation, which is generally greater in southern latitudes," wrote Dr. Hamed Khalili, of Massachusetts General Hospital in Boston, and colleagues.

"UV radiation is the greatest environmental determinant of plasma vitamin D, and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," they noted.

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.

Meat Proteins Linked to Bowel Disease in Women

A new study from France revealed that eating lots of animal protein appears to increase the risk of inflammatory bowel disease (IBD) in women. The study was conducted on 67,000 women in France over a long time period to find risk factors for different diseases, including cancer and other common illnesses. There are no conclusions that are being drawn from the study, but it does suggest that diet does potentially play a role in the disease.

An excerpt:

Women who consumed the most protein were at more than triple the risk of being diagnosed with IBD, the researchers found; animal protein accounted for most of the risk. Risk was specifically associated with high intake of meat and fish, but not with dairy products or eggs.

While experts have long suspected that diet might play a role in inflammatory bowel disease, Carbonnel and his colleagues note, the only links identified previously were with eating a lot of fats and certain kinds of sugars. Those studies were more prone to error than forward-looking or prospective studies like the current investigation. There have also been several studies linking vitamin D deficiency to IBD.

Another excerpt regarding the potential link to IBD:

Meat could contribute to inflammatory bowel disease risk because digestion of animal protein produces many potentially toxic "end products," such as hydrogen sulfide and ammonia, the researchers note. Also, Carbonnel pointed out, a high-protein diet could alter the mix of bacteria that live in the colon.

The article doesn't comment on it, but I would argue that there is potentially another possible causation here. The reasons suggested are that the high intake of proteins is either generating toxic end-products or causing dysbiosis of the bacterial mix. If that were the case, though, this type of correlation would be present with other types of animal protein sources, including dairy and eggs. But there was not. (As an aside, I would also expect that other food types - e.g. starches, sugars, etc. - also produce these types of toxic end-products as well). I think another alternative cause could be the bacteria present in meat and fish stocks. Contamination from these food sources (e.g. MAP), could also be an explanation. Hopefully that's a third alternative they'll do additional research on. Either way, interesting study.

Crohn's Disease on the Rise in Scotland

Saw an article in BBC News about how the incidence of inflammatory bowel disease has doubled in Scotland since 1980. It's unclear why there has been such an increase in that particular region relative to other European countries. But at this point, Scots are apparently the most likely Europeans to develop Crohn's Disease.

Alberta a 'hot spot' for Crohn's

Saw this article about the high prevalence of Crohn's and Colitis in Alberta and thought it was interesting. They are planning to undertake a large research study there to look for common reasons that could be contributing factors. Looking forward to seeing the results.

Distinct demographic profiles between Crohn's disease and ulcerative colitis

Just read a short article on the demographic differences between UC and CD sufferers in the UK. Additional support for environmental differences being a contributing factor. Interesting that CD was more common among "deprived social groups". Perhaps a different diet in that group? Here's an excerpt:

They found that hospitalization for severe CD was more common among women than men and it peaked among younger people aged 16󈞉 years. UC was similar among men and women and was more common among older people. There was no link between social deprivation and UC, but CD was more common among more deprived social groups.

The differing demographic profiles between CD and UC, suggest that environmental factors play a more significant role in the etiology of CD. The findings of this large population-based study on the prevalence and mortality of IBD are also important for service planning and provision.

MAP and its Relationship to Crohn's Disease

I just read a really great paper ("Mycobacterium avium subspecies paratuberculosis and its relationship with Crohn’s disease") that summarized recent literature on the role of Mycobacterium avium paratuberculosis (MAP) in Crohn's Disease. I've had several previous posts regarding MAP's potential role in Crohn's and IBD, but this paper was much more comprehensive and cited studies I had not heard of.

It's really worth reading the whole thing if you're looking for background on this topic. Here were the topics covered:

• Introduction
• MAP - description and background on the MAP bacterium
• Detection of Map in Crohn's Disease - intro of detection techniques
• MAP Culture - different methods of culturing MAP and results of studies related to Crohn's
• Detection of Insertion Sequence IS900 - methods of detecting the IS900 gene sequence (which is unique to MAP)
• Serologic Studies of MAP - looking for antibodies in the blood of Crohn's patients
• MAP and Genetic Susceptibility to Crohn's Disease - interaction between genetic susceptibility (via the NOD2/CARD15 Crohn's gene mutations) and MAP (e.g. overgrowth, etc.)
• Anti-Mycobacterial Antibiotics for Crohn's Disease - review of studies that tried (unsuccessfully) to cause long-term remission of Crohn's through use of antibiotics. MAP is very resilient and the interaction between antibiotics and immunosuppressive agents (which may also impact MAP function) leave room for doubt in the studies.
• Epidemiologic Evidence for MAP as a Cause of CD - lots of epidemiologic evidence for why MAP is likely not the cause of Crohn's, but some support of it being a cause.
• Conclusion (full excerpt below)

For reference, I'm including an excerpt of the conclusion of the paper:

MAP is the causative agent of Johne’s disease. It seems likely that chronic infection with MAP does occasionally occur in humans. MAP is widely present in our food chain and the DNA of this organism can be recovered from the intestine of CD patients. Studies have shown that a high percentage of subjects with CD are infected with MAP, though whether the association of this bacterium and CD is causal or coincidental is not known. Epidemiologists have gathered enough information to indicate an association between MAP and CD. Nonetheless, the role of MAP in CD etiology is not known, and may be determined from consistent results of studies using improved methods of isolation and detection of MAP bacilli and/or MAP-elicited immune responses in the host.

Autoimmune Disease Clusters and Crohn's

Happy Holidays! Saw this article (GWAS Meta-Analysis Supports Existence of Autoimmune Disease Clusters) today about a study conducted by Stanford University researchers. They were trying to see if there were any connections between different auto-immune diseases. Specifically, they looked at six autoimmune diseases - type 1 diabetes, rheumatoid arthritis, Crohn's disease, multiple sclerosis, autoimmune thyroid disease, and ankylosing spondylitis - and five non-autoimmune diseases to see if genetic factors related these diseases with each other.

The researchers did find that diseases go together. However, Crohn's is not related to any of these other diseases. Here's the excerpt:

Based on their analyses, the researchers suggest autoimmune diseases fall into at least two different groups: one containing rheumatoid arthritis and ankylosing spondylitis and another containing multiple sclerosis and autoimmune thyroid disease.

Meanwhile, they reported, type 1 diabetes resembled both of the groups to a certain extent, sharing characteristics with autoimmune thyroid disease but not multiple sclerosis. Crohn's disease, on the other hand, did not cluster with either group.

I suppose we're just in a category of our own =)

Johne's Disease (and MAP) in as Many as 70% of U.S. Herds

I saw an article today that shared some startling news about the spread of Johne's Disease. In the last 15 years (from 1996 to 2009), the prevalence of Johne's has increased from only 22% to as much as 70% of U.S. dairy herds. Johne's Disease is caused by the MAP bacteria (see previous blog posts), which many people have found links with to Crohn's Disease.

Here's an excerpt:

"Studies showed that in 1996, Johne's disease was in about 22 percent of the U.S. herds, but because of rapid expansion of herds across the country, producers unknowingly purchased young heifers and older cows which were infected with the disease and thus has raised the prevalence of Johne's to be present in nearly 70 percent of the herds," she said.

Could the recent rise in Crohn's Disease be linked to this rise in the spread of MAP?

Urban Cluster of Crohn's Potentially Explained by MAP

I just came across a new research report published Sept 23, 2009 (Possible Transmission of Mycobacterium avium subspecies paratuberculosis through Potable Water: Lessons from an Urban Cluster of Crohn's Disease) that found a geographical cluster of people that developed Crohn's Disease.

Here's an excerpt that describes the clustering they found (only three people, but still warrants further research):

Despite the documented presence of MAP in tap water and its probable growth on tap water pipes, clusters of Crohn's disease have not previously been described in relationship to tap water pipes supplying patients' homes. This report describes three unrelated individuals who lived on the same block along a street in a midwestern American city and developed Crohn's disease within four years of each other in the 1960's. A common tap water pipe supplied their homes. This is the first reported cluster of Crohn's disease possibly linked to fully treated drinking water, and is consistent with previously reported clusters of Crohn's disease linked to an infectious microorganism in water.

The full article can be found here.

A Link Between Food Poisoning and Crohn's

Another one I saw off of the About.com IBD blog (post). A recent study conducted in Denmark found a connection between certain types of food poisoning and increased rates of IBD.

Here is the excerpt:

Increased Risk of Inflammatory Bowel Disease After Salmonella or Campylobacter Gastroenteritis: A Population-Based Study (Abstract #80)

Researchers in Denmark have discovered a link between inflammatory bowel disease (IBD) and an initial bacterial infection with either salmonella or campylobacter gastroenteritis, an important step in understanding the development of IBD that may help explain the increasing incidence of IBD over the past decade.

Denmark’s system of tracking its citizens with individual identification numbers allowed researchers to examine patient interaction with the health-care system over a 15 year period. Investigators examined how many patients in a control group would develop IBD and compared them with those who have been exposed to bacteria in the past. They found that over 15 years, three times as many patients who had been exposed to bacteria later developed IBD as those who had not been exposed.

“This is the first time we are able to make such a clear association with an initial exposure to bacteria and subsequent development of IBD in the long term,” said Nielsen Henrik, MD, professor of infectious diseases at Aalborg Hospital in Denmark. “Our research has important implications for food safety and disease prevention. If we can reduce and prevent the spread of food bacteria and infections, we may reduce or even largely eliminate IBD in the long term.”

Dr. Nielsen is hopeful that further research will go beyond the association between bacteria exposure and IBD established in his study and attempt to prove causality by studying in detail the biology of individual patients.

I find this very interesting as I was recently thinking about several severe bouts of food poisoning I had about 5 years before being diagnosed with Crohn's. Such episodes would no doubt have some impact on the microflora in your gut.

A possible link here could be that those severe bacterial infections caused dysbiosis or some other imbalance of bacteria in the gut - perhaps killing off some good bacteria that helped to regulate the immune response in the gut. Over time, the problem that was introduced at that point compounded (or at least makes you susceptible) to other bacteria or pathogens that cause of the problem.

Cases of Crohn's Rising in Scotland, Canada (Ontario), and Northern France

I read three posts in the About.com IBD blog about recent epidemiology studies pointing to rising cases of Crohn's in Scotland and Ontario, Canada. Also came across a study that showed rising cases in youth (0 - 19 yrs) in Northern France.

Here's the post about Scotland:

Scotland Has High Incidence of Pediatric IBD

Monday July 13, 2009

Researchers in Scotland are puzzled by the dramatic increase of pediatric cases of inflammatory bowel disease (IBD) in recent years. IBD is increasing all over Europe, but the 4-fold increase in Crohn's disease in Scotland has been the most dramatic. Scottish researchers are currently recruiting for a new study to determine what may be causing the rise in IBD cases. The research will focus on the role bacteria may play in the onset of IBD. The BISCUIT (Bacteria in Inflammatory bowel disease in Scottish Children Undergoing Investigation before Treatment) Study is underway at the Royal Aberdeen Children's Hospital, with plans to expand to hospitals in Dundee, Edinburgh, and Glasgow.

And here's the post about Ontario:

Increased Rate of IBD in Ontario Children

Monday August 10, 2009

A new population-based study has shown that the rate of inflammatory bowel disease (IBD) in children in Ontario, Canada is increasing. The rate of IBD in children under the age of 18 increased from 42.1 per 100,000 in 1994 to 56.3 per 100,000 in 2005. The most striking increases occurred in preschool and school-aged children. The rates in pre-teens and teenagers showed no significant change. The authors stress that even at the increased rate, IBD is still considered rare in children.

It's already known that Canada has a very high rate of IBD, and especially pediatric IBD. The authors of this study indicate that the high immigration rates from south Asia to Ontario may be partly responsible. Research has shown that Asian immigrants to Ontario have a higher risk of developing IBD. The theory is that being exposed to the Western environment increases the likelihood of developing IBD.

And a much earlier post about Canada in general:

O Canada! Why So Much IBD?

Monday November 20, 2006

Inflammatory bowel disease (IBD) is known to be a “western” disease. In other words, it largely affects people who live in western societies. Canada appears to be a hotbed for IBD. Crohn’s disease appears to be particularly prevalent, with 13.4 per 100,000 people in Canada having the disease. In the United States, about 10 people per 100,000 have IBD. An estimated 0.5% of all Canadians have one of the two major forms of IBD. What can explain this?

The theory is that it’s the cold. The cold temperatures create a “sterile” environment which is inhospitable to bacteria. It is thought that when children are raised in an environment where they are exposed to too few bacteria, the risk of IBD is higher. Low exposure to bacteria can also occur in “too hygienic” conditions as well as cold climates.

The authors of the study published in American Journal of Gastroenterology that reported these findings indicate that hygiene and other factors may influence the development of IBD. They stress, however, that the exact cause(s) of IBD are not yet clear.

I thought the second (highlighted) paragraph in the last post was interesting. I have read elsewhere that rates of IBD are higher in northeastern areas. That's an interesting explanation for why it might be the case. Also, it could also be interesting to test dairy products in those regions to see if there is an increased presence of MAP.

Here's the text of the final study about children in Northern France:

The Changing Pattern of Crohn’s Disease Incidence According to Age in Northern France: A Constant Increase in the 0-19 Years Age Group (Abstract #114)

A population-based study of residents in northern France finds that the incidence of Crohn’s disease (CD) is on the rise, most dramatically among young people less than 19 years of age. The findings raise a number of questions about the likely causes of the increase, which the investigators say could be related to environmental factors.

Investigators from the EPIMAD registry in France tracked rates of CD among nearly six million patients in northern France between 1988 and 2005. They found that the incidence of CD among all patients increased 20.7 percent but that rates had stabilized 10 years into the study. Among young people less than 19 years of age however, the incidence of CD increased linearly by 48.5 percent.

The cause of the increased incidence of CD among young people is unknown, but investigators say aggravating factors like environmental pollution and changes in diet or smoking habits could be culprits.

“Since we now know that CD disproportionately affects young people, future studies to uncover its cause should focus on this age group,” said Guillaume Savoye, MD, EPIMAD registry and department of gastroenterology, University Hospital, Rouen, France.

All very interesting (and yet troubling) trends.