Tag: ulcerative colitis

Categories : Diet and Nutrition GastrointestinalTags : Leave a comment

Tryptophan-rich Foods might Ease Colitis… and Braai Smoke may Help too

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…although braai smoke still isn’t great for your lungs

Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Ulcerative colitis is an inflammatory bowel disease that is prone to flareups, especially around feasts. New research in mice suggests that certain foods – especially those high in tryptophan, like turkey, pork, nuts and seeds – could reduce the risk of a colitis flare. It also helps explain why cigarette smokers are less likely to have colitis. The findings, published in Nature Communications, point to a noninvasive method of improving long-term colitis management, if the results are validated in people.

“Although there are some treatments for ulcerative colitis, not everyone responds to them,” says senior author Sangwon Kim, PhD, an assistant professor of immunology at Thomas Jefferson University.

“This disease has a huge impact on quality of life, and can lead to surgery to remove the colon or cancer.”

Since ulcerative colitis is caused by inflammation of the inner lining of the colon and rectum, Dr Kim and his colleagues looked for ways to calm the inflamed tissue.

They focused on a group of immune cells called T-regulatory (T-reg) cells, which can help break the cycle of inflammation. They reasoned that getting more T-reg cells to the colon might reduce the inflammation that causes colitis.

Dr Kim’s team thought about how to attract the T-reg cells, and found a specific receptor, CPR15, on the surface of T-reg cells that acts like a magnet for the colon. The more CPR15 the T-reg cells have, the more strongly they are attracted to the colon.

So they searched for molecules that could make T-reg cells produce more GPR15 to turn up the power of the magnet. They found tryptophan – specifically, one of the molecules that tryptophan breaks down into in the body – could increase these receptors called GPR15.

To test whether these molecules could control colitis, the researchers supplemented tryptophan in the diet of mice over a period of two weeks.

They saw a doubling in the amount of inflammation-suppressing T-reg cells in the colon tissue compared to mice that weren’t fed extra tryptophan.

Dr. Kim’s team also saw a reduction in colitis symptoms, which seemed to last for at least a week after tryptophan was removed from the diet.

“In human time that might translate to about a month of benefit,” explained Dr Kim.

However, when tryptophan was given to mice during a colitis flare, it provided little benefit, suggesting this dietary change might only be effective at preventing future flares rather than treating them.

In a chance finding, while looking for molecules that could increase GPR15, the researchers also stumbled across a molecule that helps explain why smoking seems to be protective against colitis. Researchers have long observed that people who smoke cigarettes have a lower incidence of ulcerative colitis than the general public.

Dr. Kim’s team found a molecule that is prevalent in smoke – from cigarettes and barbeque alike – that can also increase GPR15 levels on T-reg cells “Although both might help protect against colitis, tryptophan is obviously the much safer and healthier option,” says Dr Kim.

In the future, the researchers plan to test whether these results can be translated to people with colitis. Tryptophan supplement is considered safe, as long as the dose doesn’t exceed 100mg per day. Using the mouse data as a guide, Dr Kim expects that 100mg could be enough to see an effect in humans, and is planning further testing in clinical trials.

Source: Thomas Jefferson University

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Atopic Dermatitis Increases Risk of New-onset IBD

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Adults with atopic dermatitis (AD) have a 34% increased risk of developing new-onset inflammatory bowel disease (IBD) compared to those without the skin condition, according to a new recently published in JAMA Dermatology. The study also shows for children, the risk increase is 44%. Additionally, as the severity of AD increased, the risk of developing IBD rose.

These findings clear up ambiguity from previous research, especially among populations of children and between the different types of IBD: ulcerative colitis and Crohn’s disease. While IBD is located in the gut and AD affects the skin, both diseases are driven by the immune system and are categorised by severe inflammation. Insight offered from this study from the Perelman School of Medicine at the University of Pennsylvania could lead to new treatments for both IBD and AD.

“It is imperative for clinicians to understand atopic dermatitis and the trajectory of our patients with it in order to provide the best standard of care,” said senior author Joel M Gelfand, MD, dermatology professor at Penn. “There are new and better treatments for AD today, and there will likely continue to be more. But providers have to understand how those treatments could impact other autoimmune diseases. For patients with AD and another autoimmune disease, some currently available medications can exacerbate symptoms of their other disease or can help treat two immune diseases at the same time.”

While this is not the first study to explore AD and IBD, its size, with one million adult and child participants with AD drawn from a UK medical database, and its separation between ulcerative colitis and Crohn’s disease advances previous research.

When looking at ulcerative colitis and Crohn’s disease separately, AD was not linked to higher ulcerative colitis in children unless the kids had severe AD. Children with AD, however, had a 54–97% increased relative risk of Crohn’s disease, and among children with severe AD, their risk was roughly five times higher. Results among adults were more straightforward. Adults with AD had a 32% increased relative risk of ulcerative colitis and a 36% increased relative risk of Crohn’s disease. Gelfand notes that the absolute extra risk of developing IBD in individuals with AD is still quite small, but the association is meaningful in better understanding health outcomes in AD. Moreover, since millions of people have AD, this small increase in risk spread among many people is likely important from a public health perspective.

Although Penn researchers did not look at the root cause of IBD linked to AD, they have strong hypotheses about the links.

“AD and IBD can cause changes in the microbiome, chronic inflammation, and the dysfunction in the skin and gut barrier respectively,” said Gelfand, who is also the director of the Center for Clinical Sciences in Dermatology at Penn. “There are also specific cytokines, certain kinds of proteins, that play a role in immune system activity and that seem to be related to AD and IBD. For example, we think dysfunction of types of T cells common to both AD and IBD, could be the culprits. Those need to be explored further to uncover both what’s happening at a microscopic level and what proteins or structures could be targeted to treat one or both conditions.”

As a leading expert on psoriasis, a disease known to be tied to IBD genetically, Gelfand is well aware of how closely skin health can affect other parts of the body. He and his colleagues are also studying AD’s relationship to infections, neurologic and psychiatric disorders, and cardiovascular disease.

“Investigating the relationship between skin diseases and other diseases doesn’t just offer new insight into how these diseases can affect a patient with both, but these studies are especially powerful because they also highlight unique characteristics of each disease and how they behave individually,” Gelfand shared.

Source: University of Pennsylvania School of Medicine

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Statins Might Reduce the Risk of Colorectal Cancer in Those with Ulcerative Colitis

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Photo by Towfiqu Barbhuiya on Unsplash

New research published in eClinicalMedicine suggests that statins might protect patients with ulcerative colitis from developing and dying from colorectal cancer. The study, by Karolinska Insitut researchers, also found that statin treatment was associated with a lower risk of death regardless of cause in patients with ulcerative colitis or Crohn’s disease.

First author Jiangwei Sun notes that previous studies have shown that the risk of colorectal cancer in patients with IBD, such as ulcerative colitis and Crohn’s disease, is 50% higher than in the general population. This is likely to be because of the chronic gut inflammation that these patients have. Researchers have long sought drugs that can reduce the inflammation-related cancer risk.

“Even though more studies are needed to confirm our results, our study suggests that statins can prevent colorectal cancer in patients with inflammatory bowel disease (IBD), which is a high-risk group for this kind of cancer,” says Dr Sun.

The observational study conducted by Dr Sun and his colleagues compared over 10 500 IBD patients from around the country, of whom half were statin users; the other half of the group, who were matched with the first, were not. After a follow-up period of, on average, 5.6 years, 70 of the statin group and 90 of the non-statin group had been diagnosed with colorectal cancer.

The effect increased over time

The protective effect was directly proportional to the length of time the patient had been on statins and could be demonstrated after two years’ treatment.

There were also fewer deaths from colorectal cancer in the statin group (20) than in the non-statin group (37) during the study period, and deaths regardless of cause (529 versus 719).

The study shows that some 200 IBD patients need to be treated with statins to avoid one case of colorectal cancer or death from the cancer within ten years of treatment onset. The protective effect was only statistically valid for patients with ulcerative colitis.

“We think this is because the study contained fewer patients with Crohn’s disease,” explains Dr Sun. “More and larger studies compiling data from patient populations in many countries will probably be needed to achieve statistical significance for Crohn’s disease.”

Significantly fewer deaths

To avoid death regardless of cause during the same ten-year period, the number of treated patients dropped to 20, on account of how statins also protect against more common conditions, such as cardiovascular disease. Statins were linked to fewer deaths in both ulcerative colitis and Crohn’s disease patients.

The study was based on the ESPRESSO-cohort, which is run by its initiative-taker Jonas F Ludvigsson, paediatrician at Örebro University Hospital and professor at Karolinska Institutet, and the study’s last author.

“In that we can combine tissue data from patients with colorectal cancer with data from Swedish health registries, we’re uniquely placed to study the long-term effects of drugs for IBD,” he says. “Our hope is that these studies will improve the care of IBD patients.”

The most solid evidence so far

According to the researchers, the new results provide the most solid evidence so far that statins could be an effective prophylactic for colorectal cancer among people with IBD. However, more knowledge must be gathered before the treatment can be recommended in general guidelines.

“More studies are needed to ascertain if there is a causal relationship, at what point of the pathological process statins should be administered, what a reasonable dose would be and how long treatment needs to last if it’s to be of benefit,” says Dr Sun.

Source: Karolinska Institut


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Would You Treat a Patient’s Ulcerative Colitis with… Hookworms?

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Using parasites to treat disease may be the stuff of mediaeval medicinal horror stories, but for inflammatory bowel disease, it might actually be a worthwhile treatment. In a feasibility study published in Inflammatory Bowel Diseases, researchers from the Malaghan Institute found that hookworms were a safe and long-lasting treatment for participants with ulcerative colitis – paving the way for wider clinical studies.

For a number of years, Malaghan Institute researchers have been investigating therapeutic benefits of human hookworms for patients suffering allergic and inflammatory disease.

“This pilot study is the first controlled evidence in the use of hookworm as a therapy in ulcerative colitis,” says Malaghan Institute clinician and gastroenterologist Dr Tom Mules who led the study alongside Rutherford Clinic gastroenterologist Dr Stephen Inns. “Our study has shown this kind of therapy is well-tolerated, safe and feasible to take into a full-scale trial.”

In this pilot randomised controlled trial, patients currently in remission from ulcerative colitis were infected with a controlled dose of hookworm larvae or given placebo, and followed up over 12 months. Patients would provide regular feedback on any changes to their gut health or discomfort. Samples were collected throughout the year-long infection to test a range of scientific parameters such as gut inflammation, microbiome and immune cell composition.

“We deliberately chose to target patients with ulcerative colitis in remission,” says Dr Mules.

“We believe that the effect of hookworms may not be strong enough to push someone from an active disease state into disease remission. However, once someone is in remission hookworm could keep them there, prevent them from having disease flares and reduce the need to take medication, such as steroids, which suppresses the immune system and has adverse effects.”

Living in remission from an inflammatory disease typically means that patients experience less pain and discomfort associated with active disease. In order to stay in remission patients generally have to take daily medications to prevent flare ups. However, Dr.= Mules explains that there are significant barriers to taking daily medication, particularly when you do not have active symptoms to remind you to take pills morning and night. Importantly, not taking the medication increases the risk of having a flare. Disease flares impact quality of life, can lead to disease complications and need strong medications to bring under control.

“One of the key findings from this study was that a single dose of hookworm can reside in the body for several years, if not longer,” says Dr Mules. “This means that if hookworm is effective at preventing disease flares you can get infected and potentially no longer have to daily medicate. ‘Infect and forget’. The worms just sit there in the background and do their thing. I think that’s where the power of this therapy lies.”

The team needed to confirm safety before they could test their “infect and forget” theory in a full-scale trial.

“We did see that around the 6–8 week mark participants reported mild tummy symptoms, but those had all resolved by week 10–12,” says Dr Mules. “Otherwise, compared to the placebo group there was no significant differences in adverse events.

“The fact that these worms are well tolerated and safe to give to people with inflammatory disease is really important. One of the big safety questions was if the immune response triggered by the hookworm in the early stages of the infection could trigger a flare of ulcerative colitis. We did not see this, again highlighting that this therapy is safe in these patients.”

With no effective cure for severe inflammatory and allergic diseases the idea of using hookworms to manage harmful and aggressive symptoms is something many people have latched onto. There exists a thriving “underground” market of people self-medicating with hookworms, and significant anecdotal evidence indicating they are helpful in treating disease and managing symptoms, says Dr Mules.

“We know that people with inflammatory bowel disease, including ulcerative colitis, already use medically unsupervised hookworms to manage their symptoms and regain some semblance of quality of life, however the evidence needed to support this is lacking. The aim of this study was to provide some solid scientific groundwork, to hopefully one day make this a real, legitimate therapy to help people living with debilitating disease.”

The team now plans larger clinical trials and applying their findings to other diseases.

“The power of our study’s findings is that we can apply them to other diseases as well,” says Dr Mules. “We are in the process of deciding what the best disease target is. It could be ulcerative colitis but there are also early findings demonstrating hookworm therapy could be beneficial to a wide-range of autoimmune, allergic and metabolic diseases.

“We’re extremely grateful to the participants for taking part in this important study which will let us apply hookworm therapy where it will have the biggest impact.”

Source: MedicalXpress

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Ulcerative Colitis Treatment Fixes Inflammation in Gut Microbiota

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Gut microbiome. Credit: Darryl Leja, NIH

Researchers have developed a new oral treatment for ulcerative colitis that takes the innovative approach of focusing on reducing inflammation in gut microbiota.

Published in Pharmaceutics, the study comprised a two-step approach to fighting ulcerative colitis. First, the researchers reduced inflammation in gut microbiota from a mouse using an anti-inflammatory drug candidate delivered by lipid nanoparticles. Then, they orally administered the end products of these treated microbiota to the same mouse, resulting in a new, effective way to prevent ulcerative colitis.

Studies have shown that irregular gut microbiota composition is linked to ulcerative colitis, and altering this composition can effectively treat a variety of chronic diseases, including ulcerative colitis. However, current methods such as faecal microbiota transplants carry a serious infection risk because they involve the transmission of drug-resistant organisms.

In this study, the researchers developed an organism-free strategy in which gut microbiota were altered in test tubes, and then microbiota-secreted metabolites were transferred back to the host. Analysis of faeces from mice with ulcerative colitis, researchers found that a natural lipid nanoparticle-encapsulated drug candidate modified the composition of inflamed gut microbiota, which were cultured outside of the host, and the secreted metabolites.

The researchers found that their M13/nLNP nano formulation shifted the inflamed microbiota composition toward being non-inflamed. This altered microbiota composition induced significant changes in secreted metabolites, and when these metabolites were fed to mice, they established strong protection against the formation of chronic inflammation.

“Our study demonstrates that modifying microbiota outside of the host using M13/nLNP effectively reshaped the microbial secreted metabolites,” commented Dr Didier Merlin, a professor at Georgia State University. “Oral transfer of these metabolites might be an effective and safe therapeutic approach for preventing chronic ulcerative colitis.”

“Our strategy to tackle the progression of ulcerative colitis might offer an alternative and complementary approach for better managing this disease,” said Dr Chunhua Yang, a research assistant professor at the Institute for Biomedical Sciences at Georgia State. “Although this study demonstrates the anti-inflammatory effects of metabolites modified outside of the organism, further investigations are required to characterise the specific bacteria that contribute to the anti-inflammatory metabolites and to identify anti-inflammatory metabolite structures.”

Source: Georgia State University