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.

Two new drugs that could be used for autoimmune and inflammatory diseases

Saw two recent articles about new drugs that could be used to treat autoimmune and inflammatory diseases, including multiple sclerosis, inflammatory bowel disease, arthritis, and others.

The first article was about a cancer drug, bortezomib, that was used in an animal study to treat inflammatory disease. The cancer drug induced cell death in only the harmful (active and proliferating) T-cells.

The second article was about a new protein from Compugen called CGEN-15001 that was found to abolish recurring relapses of multiple sclerosis in an animal study. The protein also delayed the onset of the disease. The protein apparently has some effect on the regulatory pathways in the immune system.

Both seem pretty interesting.

Virus Plus Gene Mutation Spurs Crohn's Disease in Mice

Saw an article about a new study that found a specific link between a gene mutation and virus that caused Crohn's Disease in mice. The study found that mice that had a gene variant linked to Crohn's Disease only developed Crohn's symptoms when they were infected by a specific, common norovirus called MNV.

Here's an excerpt:

Two years ago, the researchers at Washington University School of Medicine in St. Louis and others discovered that mice with an ATG16L1 gene variant associated with Crohn's disease in humans develop similar abnormalities in gut immune cells called Paneth cells. But the mutation alone wasn't enough to trigger Crohn's disease.

In a routine screening, the team later found that mice with the gene variant developed Crohn's disease symptoms within seven days after exposure to the MNV norovirus.

The study appears in the June 25 issue of the journal Cell.

It's been suspected that autoimmune and other diseases might be influenced by viral infections, but "this is the first really clear indication of a disease caused by a susceptibility gene and a specific virus," study co-leader Thaddeus Stappenback said in a journal news release.

That last statement is important. They found a specific viral infection that can trigger the disease for a specific genetic predisposition. Given there are many genetic markers for CD, there may be many possible viral infections (or bacterial infections) that can trigger the disease. So there is lots of research still to be done. But this is an important finding. As an aside, I had another recent post about a bacteria triggering arthritis in mice, so there are many angles on this research.

Nice overview of IBD, CD, and UC from Duke Research

Came across this nice 50 min overview video from Duke (my alma mater) covering different types of manifestations and management recommendations for inflammatory bowel disease, including both Crohn's Disease and Ulcerative Colitis. Highlights of note:

• minute 36:00 - The speaker comments on clinical protocol for inducing remission right around minute 36. Gives you an idea of what your doctor is basing their recommendations on.
• minute 39:30 - Non-Anti-TNF agents that are under clinical trial and study for treatment of IBD. Everything from helminthic therapy to stem cell treatment.

Broccoli extract effective against IBD and UC

Saw an article about how a plant-derived compound called Phenethylisothiocyanate (PEITC) showed potential anti-inflammatory activity and reversed many symptoms of ulcerative colitis. The PEITC compound is found naturally in the Brassica genus of plants, which includes cabbage, cauliflower, watercress, and broccoli.

An excerpt:

"I tested this substance in a mouse model that is already established and widely used. What we found is that it not only alleviates several clinical signs of ulcerative colitis — for example, it attenuates the damage that occurs in the colon tissues and colon epithelium, as well as the clinical signs like diarrhea and blood in stool. The weight loss is a major sign in colitis and that was alleviated, too," Dey added.

Good evidence to suggest that you should eat your greens! If you hate broccoli, you'll just have to get over it cause it's good for you.

Alopecia Areata and Narcolepsy both confirmed as autoimmune diseases

The list of health issues that are being categorized as autoimmune diseases are just stacking up! Saw an article a couple weeks ago that alopecia areata, a disease that causes hair loss and baldness, was caused by an autoimmune response. And a more recent article confirmed that narcolepsy is also autoimmune.

In alopecia areata, they found that some genes which attract killer immune cells are overexpressed in hair follicles. The immune cells attack the follicles and lead to rapid hair loss. In narcolepsy, the body's immune system attacks cells responsible for creating a certain hormone (hypocretin) in people's brains that's responsible for keeping people awake. The lack of hypocretin causes people to randomly and unexpectedly fall asleep.

It's amazing how many health problems are falling under the autoimmune category.

Chinese Fungus a Potential Immunosuppressant to Treat MS

Saw an interesting article in the Wall Street Journal about a new drug being introduced by Novartis called fingolimod. The drug is used to suppress the immune system, treating some of the symptoms of multiple sclerosis. I'm generally not a big fan of immunosuppressants, but the article does suggest why many alternative therapies work.

The drug is based on a fungus known as "winter-insect-summer-plants". An excerpt describing the fungus:

Dr. Fujita says he reasoned that an even more powerful immunosuppressant chemical ought to be present in a group of Asian fungi known in Chinese and Japanese as "winter-insect-summer-plants." These fungi attack insects in the winter with their chemical arsenal. By summertime, the insect is dead and its corpse has been transformed into a vessel for the blooming fungus. Ironically, the same properties that make the chemical deadly in the insect world may also have a helpful side for people suffering from certain autoimmune diseases, in which an overactive immune-system response causes the body to attack its own cells.

There are many natural remedies used in Chinese and Japanese medicine, including herbs and fungus. Perhaps many of these work because they are immunosuppressive.

When Good Germs Go Bad - Friendly Bacteria Triggers Arthritis in Mice

Saw a really interesting article in Scientific American about a study regarding a link between a specific strain of bacteria and rheumatoid arthritis (RA) in mice. The study found that the introduction of a single type of bacteria could increase the amount of IL-17 (interleukin 17), a protein that signals the immune system to cause inflammation, in the mouse. The "friendly" bacteria that causes this accelerated the onset of arthritis in the mice. The mice were selected to already be genetically predisposed to having arthritis, so all mice in the study developed arthritis. But the mice that were given the bacteria developed RA much more quickly.

Why is this important? This could mean that exposure to even a single bacteria or virus could trigger an autoimmune reaction in genetically susceptible individuals. Here's an excerpt:

Mathis emphasized that one should not take away from these mouse studies "that mice or humans can 'catch' an autoimmune disease or arthritis," she says. She added that the better way to think about it is that individuals have varying degrees of genetic susceptibility, and when exposed to certain environmental factors may then go on to develop disease. "It's really an interaction between genetics and environment," Mathis says.

Crohn's Disease or Inflammatory Bowel Disease (IBD) may have a similar pattern to RA. It could also mean that there is a single bacteria or virus responsible for the disease. Or ... it could also mean that there are any number of bacteria or viruses that trigger the disease. Either way, it's a very study and reinforces previous theories and studies I've seen.

Prostaglandin D2 a potential treatment for Ulcerative Colitis

A recent study may suggest a new treatment for ulcerative colitis. The study, to be published in the journal Proceedings of the National Academy of Sciences, found that people with ulcerative colitis that have been in remission for a long time-period have higher levels of Prostaglandin D2 than those that don't. It's unclear whether the higher levels of the chemical are a result of being in remission or the cause of the remission, but the study is interesting nonetheless as it suggests follow-on research.

FDA requires cancer warning on TNF blockers (old news)

I've thought for a while that TNF blockers and other immunosuppressive drugs may actually be counterproductive in the long-run in treating Crohn's Disease and IBD. The point of TNF-alpha in the immune system is to promote the fight against tumors (TNF = tumor necrosis factor). What happens if you suppress that immune response? Your body may be missing tumors that it should be fighting. A recent article prompted me to take a look at the FDA warnings for TNF-alpha blockers. Apparently, the FDA started requiring cancer warnings on TNF blockers back in August of 2009 -- here's the FDA press release. I think dozens of cancer cases in children taking TNF-blockers prompted the FDA to add the box warning.

I definitely see the value of these drugs in the short-term to help get the inflammation under control, but long-term use doesn't seem like a solution. (Hence why I'm avoiding them!)

Why Pregnancy Pushes Autoimmune Diseases into Remission

A friend of a friend of mine has had Crohn's for many years. But when talking to her, she mentioned that during her pregnancy all her Crohn's symptoms completely subsided and she was in "remission". Why? This apparently is a common phenomenon for pregnant women with autoimmune diseases -- during pregnancy their diseases go into remission.

A new study from the University of Michigan may explain why. Apparently the expression of an enzyme called pyruvate kinase is reduced in immune cells in pregnant women. The reduction in this enzyme "dials-down" the immune system supporting the acceptance of the fetus.

An excerpt from the article:

In his search to explain the phenomenon, Dr. Petty knew to look for a metabolic pathway ormechanism with two characteristics. It had to "dial down" the intensity of the normal immune response, an action needed so that a pregnant woman does not reject the fetus, which has proteins from the father that are "foreign" to the mother. At the same time, such a mechanism must support cell growth needed by the developing fetus.

The activity of the enzyme pyruvate kinase–and its product, pyruvate–fills both roles: promoting cell growth while modifying the immune response. Because pyruvate kinase activity is depressed duringpregnancy, cell metabolism supports an increased production of lipids, carbohydrates, amino acids, and other substances that support cell growth.

This suggests an interesting alternative therapy or treatment option for the future (and I'm not suggesting that you just go get pregnant!). There may be a way to use this immune pathway in a drug therapy. It doesn't necessarily identify or address the root cause of IBD, but it could lead to another alternative therapy.

Gene Mutations Offer Clues to Autoimmune Disease

Saw a couple articles (BusinessWeek, Wired.com, ScienceNews) commenting on a story in Nature about a study that found that variations in a single gene could result in different types of autoimmune diseases, including Crohn's Disease and diabetes.

An excerpt:

The gene in question encodes an enzyme called sialic acid acetylesterase or SIAE, which regulates the activity of the immune system’s antibody-producing B cells. About 2 percent to 3 percent of people with autoimmune disorders have defects in the enzyme that allow B cells to run amok and make antibodies that attack the body, a team led by Shiv Pillai of Massachusetts General Hospital in Charlestown and Harvard Medical School reports online June 16 inNature.

“It’s a seminal paper because it is so applicable to a wide variety of autoimmune diseases, says Judy Cho, a Yale geneticist not associated with the study. The finding suggests that enhancing the enzyme’s activity could help treat disease in people with autoimmune disorders.

Definitely an interesting finding!

Resveratrol Improves Inflammatory Bowel Disease Symptoms

Saw an article about a new study that found that resveratrol, an antioxidant found in grapes, improved symptoms of inflammatory bowel disease (IBD).

Here's an excerpt from the article:

Resveratrol is a phytonutrient (phyto means “plant”) that is the subject of considerable research because of its anti-inflammatory, antioxidant, anti-tumor, and immune system boosting properties. Previous studies have suggested that resveratrol enhances brain function and builds resistance to stroke, helps withweight loss, inhibits prostate cancer cell growth, and protects against diabetes.

Resveratrol’s anti-inflammatory abilities are of special interest for possible treatment and prevention of inflammatory bowel disease, of which ulcerative colitis and Crohn’s disease are the two most common types. In the current study, which appears in theEuropean Journal of Pharmacology, researchers conducted a placebo-controlled study in which one group of mice were given 20 mg of resveratrol per kilogram of food and the other group received placebo. The study period lasted 30 days.

Grape juice is my primary dietary source of carbohydrates (because it is SCD compliant), so this is encouraging news. It also reinforces why the SCD diet may work.

Virus infection may trigger unusual immune cells to attack the brain and spinal cord in multiple sclerosis

I came across a really interesting article regarding a possible causative mechanism for multiple sclerosis (MS). As you most likely know, MS is an autoimmune disease (similar to IBD and Crohn's) where immune cells misguidedly attack the body's own cells. In the case of MS, the body is attacking the protective sheath around major nerves. In the case of IBD, the body is attacking your intestinal tissue.

The above mentioned article found that a viral infection could incite certain rare immune cells to be released in the body that attack both the virus and (in the case of MS) nerve cells. The rare immune cells do this because they have receptors for both the virus' proteins and proteins present in nerve tissue (myelin). I found this research interesting given the recent talk from Amy Proal that I blogged about regarding the viral and bacterial metagenome and the recent study (similar to the MS one) that found a possible link between errant T-cells and diabetes.

The study about MS suggests that there's not necessarily a single virus that causes the disease, but instead a combination of factors that generate the errant T-cells:

The authors explained that it's possible that multiple viruses could influence susceptibility to multiple sclerosis. The ability of any particular virus to contribute to the disease could depend on an individual's own repertoire of other predisposing genes, exposure to other predisposing environmental factors, and the random chance that T cells had been generated that recognize a myelin protein and a pathogen.

Receptors on T cells are randomly generated during their development. This observation helps explain why multiple sclerosis is partly a matter of chance. Some people with a genetic predisposition and environmental exposure develop the disease, while others with similar genetic predisposition and environmental exposure do not.

This suggests some really interesting (and challenging) directions for future research. Many current studies are focusing on finding a single bacteria or virus (e.g. MAP) that someone is infected with or a single genetic mutation (e.g. NOD2) that cause IBD. This is a potentially flawed approach, though. This study suggests that even after the infection is cleared, the errant T-cells that cause the autoimmune reaction may persist (i.e. there's no smoking gun). It certainly makes finding the root-cause difficult! But it suggests a different direction to take research.

Teaching Kids to Cope with IBD

Saw this article about a study conducted at the University of Georgia with teenage girls suffering from IBD. They found that teaching the young girls "coping" and "community" skills had a positive impact on their physical symptoms. They also found that mental distress decreased -- as they called it "catastrophic thoughts" (pretty scary sounding if you ask me).

Here's an excerpt:

"We saw significant improvements in these adolescents' physical symptoms and coping strategies following treatment," said Ronald Blount, professor of clinical psychology at UGA and an author of the study. "Parents, who were also involved in the study, reported reductions in catastrophic thoughts related to their daughters' pain and improved behavioral reactions related to their daughters' physical symptoms. We aimed to teach parents to become coaches for their daughters to help them better manage their symptoms."

Inflammatory bowel disease is a pretty life changing illness, though, and one quite difficult to talk about with others (particularly if you're a teenager), so I can certainly appreciate how important it is to teach young people these coping strategies. Stress certainly may play a contributing role in the disease, so stress reduction strategies may be helpful. The next step for the researchers is to expand the study to a larger population.

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.

Probiotic in breastmilk reduces painful cramps

Thought this one was interesting. Apparently the bacteria Lactobacillus reuteri found in breastmilk decreases the force of muscle contractions associated with inflammatory bowel disease (IBD). It is passed on from mother to baby in breastfeeding. Interesting, but might be a tough one to add to your supplement list.

Here's an excerpt:

"It might not be possible for most of us to get breast milk from the tap," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but we can still benefit from some of the life-supporting substances it carries. This research shows that the relationship between humans and microbes can be beneficial for both. The Lactobacillus finds a new home, and we're no longer up tight."

Amy Proal on Viral and Bacterial Metagenome

Just watched a really interesting talk by Amy Proal about how the interaction and symbiosis (i.e. reinforcing relationship) between bacteria and viruses could lead to autoimmune disorders by interfering with Vitamin-D receptors (VDR's). I've embedded the video below, but here's a link to the post. It looks like she's working on some really interesting research.

The idea is that autoimmune disorders are caused by multiple bacteria and viruses working together to suppress the immune response. This causes a vicious cycle as it supports additional bacterial and viral infection. She suggests that traditional therapies like immunosuppression (which I have mentioned repeatedly seems counterintuitive) may actually prolong and worsen diseases in the long run. They have been working on alternative therapies that are meant to boost the innate immune response. Her blog seems pretty interesting as well, so worth a look as well: http://bacteriality.com/.

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.

Antibiotics in Infancy Potentially Linked to IBD Risk

A small study showed that there might be an increased risk of IBD for infants that are given antibiotics in their 1st year of life. The study compared 36 children with IBD with 360 children that did not have IBD. 60% of the group with IBD had been given antibiotics compared to only 40% for the non-IBD group. The difference was even more pronounced for boys than girls. The study suggests a possible root cause or causative agent in the development of the disease. But again, this was a very small study, so this just suggests areas for additional research.

Anti-TNF Decreases Presence of MAP

I only saw the abstract of this one. There was a study that found that taking anti-TNF drugs, in this case infliximab (i.e. Remicade), reduced the occurrence of mycobacterium avium paratuberculosis (MAP) bacteria in people suffering from Crohn's. Specifically, they just measured the change in MAP antibodies in the blood, but it would suggest that Remicade supported the body's fight against any MAP infection. I've had a couple posts on MAP, so I like to monitor research in this area. Interesting finding that supports the efficacy of these drugs (although admittedly I don't take them).

Discovery Prompts New Theory on Cause of Autoimmune Diseases

Saw an article in ScienceDaily about a new theory on the cause of autoimmune diseases, including Crohn's Disease. Researchers discovered a protein (or peptide) fragment that's capable of causing diabetes in mice. The basic hypothesis is that the unusual introduction of these peptides allows errant T-cells to escape the thymus and make there way to other parts of the body where they initiate immune responses associated with autoimmune diseases. These errant T-cells that are autoreactive (or that react to your body's own cells) are normally deleted by the immune system. However, the introduction of these rare peptides causes the deletion procedure to not work properly.

Here's an excerpt:

In the April 23, 2010, issue ofImmunity, Drs. Brian Stadinski, John Kappler and George Eisenbarth propose that the unusual and rare presentation of protein fragments (peptides) to the immune system allows autoreactive T cells to escape the thymus and trigger autoimmune disease. The findings could lead to a new strategy for preventing type 1 diabetes.

"The immune system normally deletes dangerous, autoreactive T cells that recognize 'self' peptides, which are a normal part of the organism," said Dr. Kappler, Professor of Immunology at National Jewish Health. "We believe autoreactive T cells in diabetes and other autoimmune diseases escape destruction in the thymus because they never see these poorly presented peptides there. But the T cells do encounter those peptides elsewhere in the body and trigger an autoimmune attack."

Pretty fascinating if the theory is correct. It could also suggest very new areas of research for treatment options.

Olive Oil Good, Aspirin Bad

Saw results of two different studies. One was about how Olive Oil (specifically oleic acid) helps to prevent inflammatory bowel disease. The second was about how aspirin increases the risk of Crohn's Disease by five times!

Recent Review of Diet's Role in Inflammatory Bowel Disease

Came across this recent survey (PDF) of the different dietary causes and treatments of inflammatory bowel disease, including Crohn's Disease. Nice article that touches on several different dietary alternatives and their efficacy (when tested in controlled studies). Here's the abstract of the article (cut-and-pasted):

Many studies have looked at connections between diet, etiology, signs and symptoms associated with inflammatory bowel disease (IBD). Although these connections are apparent to clinicians, they are difficult to prove qualitatively or quantitatively. Enteral feeding and polymeric diets are equally effective at bringing about remission in Crohn’s disease (CD). Parenteral feeding is also effective, although none of these methods is as effective as corticosteroid therapy. However, enteral feeding is preferred in the pediatric population because linear growth is more adequately maintained via this route. Exclusion diets in patients brought into remission using an elemental diet have been shown to maintain remission for longer periods. Studies that aim to isolate culpable food groups have shown that individuals react differently on exposure to or exclusion of various foods. The commonly identified food sensitivities are cereals, milk, eggs, vegetables and citrus fruits. Studies that have looked at gut mucosal antigen behavior have shown higher rectal blood flow, in response to specific food antigens, in those with CD over healthy subjects. Exclusion of sugar shows little evidence of amelioration in CD. Omega 3 fatty acids show promise in the treatment of IBD but await larger randomized controlled trials. Patients frequently notice that specific foods cause aggravation of their symptoms. Whilst it has been difficult to pinpoint specific foods, with advances in the laboratory tests and food supplements available, the aim is to prolong remission in these patients using dietary measures, and reduce the need for pharmacotherapy and surgical intervention.

Of course the conclusion of the study basically just says "we need to do more research", but that's to be expected.

PPAR-gamma Protein Key to Inflammatory Bowel Disease

Researchers have found a new potential treatment option for inflammatory bowel disease. The protein PPAR-gamma was found to help restore the body's natural defenses against gut infections from bacteria and could be used as a treatment for Crohn's Disease.

Here's an excerpt:

Samples taken from the colons of humans diagnosed with Crohn's disease also show reduced levels of the antimicrobial peptides, or defenses, regulated by the PPAR-gamma protein, they wrote.

Chamaillard said foods or diets containing conjugated linoleic acid (CLA) can also boost PPAR-gamma activity and have been shown to improve colitis and colitis-associated cancer.

CLA is primarily found in milk and meat products.

"In the short-term, managing the disease is what we are looking at, but it may also be that in the future we could develop a way of stopping it," Chamaillard said.

But he added that curing Crohn's disease would mean being able to identify those at highest risk before they contracted it and then being able to boost PPAR gamma-related defenses to ward it off -- both areas that would need more research.

So how could you add more CLA to your diet? I checked out the CLA Wikipedia page and found the following:

Of all foods, kangaroo meat may have the highest concentration of CLA.^[34] Food products (e.g. mutton and beef) from grass-fed ruminants are good sources of CLA, and contain much more of it than those from grain-fed animals.^[35] In fact, meat and dairy products from grass-fed animals can produce 300-500% more CLA than those of cattle fed the usual diet of 50% hay and silage, and 50% grain.^[36]

Eggs are also rich in CLA, and it has been shown that CLA in eggs survives the temperatures encountered during frying.^[37]

Some mushrooms like Agaricus bisporus and Agaricus blazei, are rare vegetable sources of CLA.^[38][39]

Very exciting to see research being done (and producing results) regarding natural methods of treating Crohn's. I'm looking forward to seeing how this research advances. In the meantime, stock up on the kangaroo burgers.

Pathobionts, Dysbiosis, and IBD

Saw an article about some research at Caltech. Biologists have identified bacteria that lie between the traditional categories of "symbionts" and "pathogens". An example is the Helicobacter hepaticus bacterium. An excerpt:

"The bacteria appear to have struck a deal with their host," Mazmanian says. They keep their own numbers low so they don't overwhelm the immune system, and in return, the immune system leaves them alone. "The bacteria need the secretion system to put the host in 'don't attack' mode." In return, the presence of the bacteria does not induce inflammation, as would be the case with a pathogen that has not evolved a similar "agreement."

"There has to be communication. It could be peaceful—as is the case for symbionts—or it could be an argument—as is the case for pathogens. But when this molecular dialogue breaks down, it's probably harmful to both microbe and man," Mazmanian says.

Disrupt that communication, and the balance gets thrown out of whack. "Inflammation leads to cancer, and this bacterium has been associated with inflammation and colon cancer in animals," he says. Understanding if dysbiosis causes disease in humans could lead to therapies based on restoring the healthy microbial balance in the gut.

Stress Aggravates IBD

Saw this article commenting on an upcoming study that will be published in the American Journal of Gasteroenterology. The study found that stress was linked to a more than twofold increase in the risk of symptom flare ups in IBD sufferers. Here's an excerpt:

Stress had long been among the main environmental factors linked to the flare-up of symptoms in some individuals. This theory, however, had never been clinically proven.

According to the study published in the American Journal of Gastroenterology, stress is associated with a more than twofold increase in the risk of symptom flare ups in sufferers.

Such a link was not seen in other factors suspected of triggering IBD symptoms such as the use of antibiotics or non-steroidal anti-inflammatory painkillers, and infections including colds, pneumonia and urinary tract infections.

"This is among the first evidence to show that the perception of stress had a direct association with disease course," said lead researcher Charles N. Bernstein, stressing that learning better stress management methods could help treat the condition more effectively.

Here's an excerpt from another article on the same topic suggesting a possible reason for the connection:

There are biological reasons to believe that a person's response to stress would trigger or worsen IBD symptoms, Bernstein and his colleagues note.

The sympathetic nervous system, which jumps into action during times of stress, acts on the lining of the colon, and might exacerbate existing inflammation. There is also evidence that stress hormones may help harmful bacteria take up residence in the intestines, which might, in turn, affect symptoms.

Combination Drug Therapy for Crohn's

Read a few articles (USNews, WebMD) about a new study that showed that a combination of azathioprine and biologics are more effective in treating Crohn's Disease than taking each individually in succession. Normally doctors treat Crohn's by prescribing steroids. If steroids don't work, doctors will move on to azathioprines and then finally biologics if the other two don't work.

Here's an excerpt:

Doctors now start treatment of Crohn's disease with steroids, Sandborn said. If the steroids do not provide relief from the abdominal pain, nausea, fever, weight loss, diarrhea and othersymptoms of the condition, the next step is to use azathioprine, which reduces immune system activity broadly. Only if that fails will they try biologics, newer treatments that include monoclonal antibodies such as infliximab (Remicade). These drugs target a specific part of the immune system.

The trial showed that the azathioprine-alone step should be skipped. "This study suggests that the therapy that follows steroids should include a biologic," Sandborn added.

Therapy with both azathioprine and infliximab appears to be the treatment of choice if steroids are not effective, Sandborn said.

"What this trial shows is that the most effective strategy is combination therapy," he said.

Definitely an interesting finding and good that doctors are finding a more optimal way to treat with traditional medicine.

Genetic Variation Not the Only Cause of Crohn's Disease

Saw an article that commented on a recent study of Danish people and thought it was interesting. The basic conclusion was that the NOD2/CARD15 gene variations previously considered a marker for Crohn's Disease actually do not have a statistically significant association with the disease ... at least for the Danish population. This certainly runs counter to previous studies.

Here's an excerpt:

The study, was conducted to estimate the likelihood that three particular genetic variants in the NOD2/CARD15 gene are related to the risk Crohn disease in the general population.

The population-based study genotyped 43 596 Danish people followed between January 1976 and July 2007. Using a logistic regression model (used to predict the probability of an occurrence) physicians estimated the risk of Crohn disease in the general population.

"Surprisingly, we found no statistically significant association between NOD2/CARD15 genetic variants and Crohn disease in either of the two general population studies that we analyzed, which suggests a low penetrance of the genetic variants in the European general population," write Dr. Børge G. Nordestgaard, Herlev Hospital, University of Copenhagen, Denmark and coauthors. (Penetrance is the degree to which the gene causes the disease.)

The authors conclude that the penetrance of NO2D/CARD15 genetic variants in relation to risk of Crohn for the Danish population was lower than might have been expected from previous European case-control studies. This should be considered when advising healthy individuals in whom these genetic variants are discovered.

What might this mean? Does this mean that genetic variations do not play a role in Crohn's Disease. Not necessarily. More likely it means that there are many contributing factors and many possible causes - not just one genetic variation. Another excerpt from the note:

In a related commentary http://www.cmaj.ca/embargo/cmaj100300.pdf, Dr. Katherine A. Siminovitch and coauthors write that these research findings reinforce the fact that common diseases have many causes and that in these diseases, the effect of any single gene variant on risk is usually small. This underscores the current challenge in realizing the potential of personalized medicine (use of an individual's specific information to select or optimize preventive care and therapy).

It'll be interesting to see how the research community comments on this in relation to previous studies.

Nlrp3 protein and Crohn's disease

Saw an article about the Nlrp3 protein and it's relationship to Crohn's and Colitis. Here's the full press release. Here's an excerpt:

Researchers demonstrated that in a mouse model of colitis, Nlrp3 plays a pivotal role in keeping the intestinal tract intact, thus preventing further damage that occurs if intestinal bacteria leak into the body.

Nlrp3 works by anchoring a large, multi-protein complex known as the Nlrp3 inflammasome where the messenger protein interleukin 18 (IL-18) is made.

IL-18 belongs to a family of molecules known as cytokines, which shape the body's immune response. In this study, researchers showed IL-18 produced by the Nlrp3 inflammasome helped mice maintain healthy colon by triggering production of more epithelial cells to compensate for those damaged or destroyed by colitis.

"This paper provides the basis for more effective, potentially disease-modifying approaches to treatment," Kanneganti said.

Helminthic Therapy Spot on CBS 5 News

This is a pretty old spot from CBS 5 in San Francisco, but thought it was interesting. For more info on this topic, see my old post - "I'll Take a Parasite Please: Helminthic Therapy and the Hygiene Hypothesis".

Gene Sequencing Yields Picture of Human Gut

Read this article in Business Week about how researchers have identified 160 different species of bacteria in the gut. One interesting finding - people with inflammatory bowel disease (IBD) have 25% fewer bacterial genes than healthy people, indicating that those with IBD have less diversity in their gut.

An excerpt:

"This is so rich. It could help in so many different ways. It could help us understand diseases like inflammatory bowel disease [IBD], Crohn's and ulcerative colitis. It could help us with problems like malnutrition and obesity. It could help us understand many different metabolic problems from liver disease to kidney to heart disease," said Dr. Martin Blaser, chairman of the department of medicine at New York University Langone Medical Center and a professor of microbiology at New York University School of Medicine in New York City. "This is really a landmark study."

Italian researchers discover a possible onset mechanism for Multiple Sclerosis

I just read an interesting article on how bacterium might be a trigger for the onset of Multiple Sclerosis. One theory regarding the cause of MS is that it is an autoimmune triggered. A recent study in mice found that a harmless bacterium made to look like a nerve cell allows T-cells to modify to the point where they can repeatedly break into the central nervous system. Normally, T-cells can not do this. However, in mice where this modified bacterium has been introduced, the T-cells modify in the inflammatory response. These modified T-cells persist well after the bacterium has been killed and continue to cause inflammation in the central nervous system.

I think it's interesting to see how other immune disorders operate as there may be analogs in Crohn's.

Here's an excerpt:

This is the hypothesis that the researchers coming from the Institutes of General Pathology, Microbiology and Anatomy of the Catholic University of Rome have been testing with their two-year long work. To demonstrate the viability of this idea, scientists have fooled the mouse immune system, modifying subtly a bacterium of the common family of mycobacteria (the same family to which also the bacterium causing tuberculosis belongs) to make it look like to myelin, the protein coating nerve cells. This modified mycobacterium is completely innocuous. As all external agents, though, it is capable to trigger the reaction of the T-cells of the immune systems. They intervene to destroy it. Since they are innocuous bacteria, although very common in the environment, and since they induce an immune reaction, they are the ideal bacteria scientists can use to study the environmental factor contributing, together with the genetic factor, to cause multiple sclerosis.

"Normally, T-cells cannot penetrate into the Central Nervous System", adds Rea, "because the hematoencephalic barrier prevents them from doing so. But the bacterium modifies the characteristics of the T-cells and allows them to overcome the barrier. In 15 days the bacterium disappears completely from the body".

Yet these T-cells can now enter into the brain. This way, they begin to attack the myelin of the nerve cells, and here is how the immune disease breaks out.

"We basically demonstrate – explains Rea – that in an animal model it is possible to be infected with something not carrying any disease, and later on develop a purely autoimmune disease".

Pretty interesting.

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.

TRPV2 Protein Trips Up Germs

Another article on proteins related to the immune response. TRPV2 allows macrophages to get a better grip on bacteria, allowing the immune response to be more effective. There's no direct relationship found at this point with autoimmune diseases like Crohn's, but you never know. So thought I'd post it.

Here's an excerpt:

Citing the fact that TRPV2 is important not only in helping macrophages to bind to germs, but also in clearing bacterial infection, Caterina noted its potential as a useful drug target. And in cases of autoimmune diseases -- arthritis, lupus and asthma, for example -- it's possible that the inhibition of TRPV2 might help pull back an overactive immune system.

"We think there are going to be a lot of implications beyond just prevention of infectious diseases where this research about TRPV2's function in macrophages might be relevant," Link adds. "Macrophages consume cholesterol and contribute to hardening of the arteries. They also clear out debris when nerves are injured so that new nerves can grow through that area."

GM-CSF Protein Appears Key to Intestinal Balance

Saw this article and thought it was interesting. It's about a protein called granulocyte-macrophage colony-stimulating factor (GM-CSF) that helps regulate gut inflammation.

Here's an excerpt:

Reduced levels of the protein — granulocyte-macrophage colony-stimulating factor (GM-CSF) — could be an underlying factor in severe illness caused by pathogens such as E. coli and intestinal inflammation in inflammatory bowel diseases such asCrohn’s disease, the researchers said.

“The gut normally is in a chronic state of low-grade inflammation that is beneficial,” study author Dr. Martin Kagnoff, professor emeritus of medicine and pediatrics at the University of California, San Diego, School of Medicine, said in a university news release.

“This study shows that GM-CSF has a profound influence in the regulation of cells that determine whether the gut lives in peace with this inflammation or becomes severely inflamed during infection,” he said. “Any time that delicate balance is disrupted, all heck can break loose.”

Kagnoff said the findings might help explain why some people with Crohn’s disease benefit from receiving GM-CSF. A greater understanding of the role of GM-CSF in the gut could lead to new treatments based on the protein, he added.

Link Between Inflammatory Disease and Premature Aging

Some research from University of Arizona suggests that inflammatory diseases, including inflammatory bowel diseases like Crohn's Disease, could lead to a premature aging process. The researchers found that the Klotho gene, a gene which plays a vital role in aging, was down-regulated. This could speed the onset of age-related diseases like osteoporosis.

Here's one excerpt:

"We have made a novel discovery," said Dr. Fayez K. Ghishan, professor and director of the Steele Center. "Based on our research, it appears that chronic inflammation of the gut causes Klotho to down-regulate – or ‘turn off' – contributing to premature-aging diseases such as osteopenia, osteoporosis and atherosclerosis, to name a few."

And another excerpt:

"We can now theorize that if you have an inflammatory process going on, like IBD or rheumatoid arthritis, for example, you are likely to develop symptoms of premature aging," Kiela said. "Our findings lay the foundation for future work related to the contribution of Klotho to chronic inflammatory diseases in human patients – and how to better treat these diseases."