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.”
Wednesday, November 10, 2010
Monday, August 2, 2010
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.
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.
Tuesday, July 13, 2010
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.
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.
Thursday, July 8, 2010
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.
- 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.
Wednesday, July 7, 2010
"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.
Tuesday, July 6, 2010
Wednesday, June 23, 2010
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.
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.
Monday, June 21, 2010
Thursday, June 17, 2010
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.
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.
Tuesday, June 15, 2010
Virus infection may trigger unusual immune cells to attack the brain and spinal cord in multiple sclerosis
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.
"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."
Monday, June 7, 2010
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.
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.
Thursday, June 3, 2010
"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."
Wednesday, June 2, 2010
Tuesday, May 18, 2010
Monday, May 10, 2010
Thursday, May 6, 2010
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.
Tuesday, May 4, 2010
Saturday, May 1, 2010
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.
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.
Of all foods, kangaroo meat may have the highest concentration of CLA. 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. 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.
Sunday, April 25, 2010
"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.
Sunday, April 18, 2010
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.
Thursday, April 15, 2010
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 other 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 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.
Wednesday, April 7, 2010
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.
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).
Saturday, March 20, 2010
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.
Sunday, March 7, 2010
Friday, March 5, 2010
"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."
Saturday, February 27, 2010
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".
Thursday, February 25, 2010
Saturday, February 20, 2010
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."
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.
Saturday, February 6, 2010
"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."
"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."