Tag: Crohn's disease

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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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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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Nanomedicine Stimulates Anti-inflammatory Effects to Ease IBD

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Chronic inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, is on the rise worldwide, and current medications have problematic side effects. In the journal Angewandte Chemie, researchers report a new method of treatment, based on nanoparticles which trigger anti-inflammatory effects in the diseased sites in the intestine.

Stomach cramps and severe diarrhoea, often accompanied by significant weight loss, are some of the symptoms repeatedly suffered by patients with IBD, often for weeks at a time. The causes of this condition remain unclear but seem to involve a malfunction of the immune system. A cure is not yet in sight. Current treatments aim to reduce symptoms with anti-inflammatory medications, such as 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators. Their long-term use is not recommended because of their severe side effects, such as a high risk of infection resulting from immunosuppression. A team led by Hee-Seung Lee and Sangyong Jon at the Korea Advanced Institute of Science and Technology (KAIST) has now developed an innovative approach for a medication that can be taken orally and targets the inflamed sites in the gastrointestinal tract, minimizing systemic effects.

The starting point of their approach was the glycocalyx, a carbohydrate-rich layer that coats the cells on the surface of the intestine. Beneficial gut bacteria, which have their own matching glycocalyx, attach to this coating. With diseases from the IBD family, the glycocalyx carbohydrate patterns of inflamed intestinal regions are so altered that pathogenic bacteria can attach and enter the mucous membrane.

The team developed nanoparticles that mimic the glycocalyx pattern. Starting with the five sugar monomers most commonly found in nature, they produced a collection (“substance library”) of different polymer chains that have one, two, three, four, or five of these sugars in random order and composition as side chains. These polymer chains aggregate into nanoparticles. They also attached bilirubin molecules. Bilirubin is a bile pigment that is an antioxidant naturally produced by the body and it has an anti-inflammatory effect.

When administered orally to mice with IBD, some versions of these nanoparticles reduced symptoms significantly better than the drug 5-ASA. Nanoparticles with mannose and N-acetylglucosamine were the most effective. These two sugars increase uptake of the nanoparticles by activated macrophages in the inflamed intestine, and bilirubin very efficiently inhibits the inflammatory activity of these immune cells. The concentration of certain inflammatory cytokines is significantly reduced, the production of anti-inflammatory factors is stimulated, and oxidative stress is reduced. The immunosuppressive effect is limited to the inflamed areas of the intestine, minimising unfavourable systemic side effects.

Source: Wiley

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Higher Risk of Lymphoma in Patients Suffering from IBD

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Karolinska Institutet researchers have found that the risk of developing lymphoma is slightly elevated in inflammatory bowel disease (IBD) and, in recent years has been on the rise in patients with Crohn’s disease. Publishing in Clinical Gastroenterology and Hepatology, the researchers also observed a risk increase in patients taking modern IBD drugs, which was less strong for those not taking them. Thus, the lymphoma risk could be affected by both the medication and the disease activity itself.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a chronic intestinal inflammation that can increase the risk of developing lymph node cancer (lymphoma), a disease that affects the immune system.  

“Previous studies of the lymphoma risk of IBD have been too small to draw reliable conclusions,” says the study’s first author Ola Olén, consultant and docent at the Department of Medicine (Solna), Karolinska Institutet. “The studies have not taken into account of important systematic errors or been representative of today’s IBD patients.”  

The present study included almost 170 000 IBD patients identified in Swedish and Danish national registries between 1969 and 2019. Compared to patients with a matched population without IBD, patients with both Crohn’s disease and ulcerative colitis had a higher risk of lymphoma. The highest risk was in patients with Crohn’s disease, the increase being driven mainly by T-cell lymphoma and aggressive B-cell lymphoma.

“We found an elevated relative risk of different types of lymphoma in both Crohn’s disease and ulcerative colitis, but we need to point out that the absolute risk is very low,” says the study’s last author Jonas F Ludvigsson, consultant and professor at Karolinska Institutet.

“The increase in risk equates to only one extra case of lymphoma in 1000 people with IBD, who were followed for ten years.”

“Both inflammation and treatment play a part”

The risk of lymphoma has increased in patients with Crohn’s disease over the past two decades, which coincides with the increasing use of immunomodulating drugs for IBD. While the highest risk of developing the cancer was observed in patients who had received these drugs, the researchers found that patients who were not on such medication were also at a higher risk of lymphoma. 

“This finding indicates that both the inflammation in itself and its treatment play a part,” says Dr Olén. “Since there’s a lot of talk about the lymphoma risk associated with immunomodulating drugs, it’s important to make it clear that also the disease and the inflammation per se seem to drive the development of lymphoma. One has to take account of this and discuss it when prescribing modern treatments where there might be a concern that they will increase the risk of lymphoma.” 

Dr Olén says the teamaims to use more detailed data to determine whether the disease itself or its treatment is more important in terms of lymphoma risk.

Source: Karolinska Institutet

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Caesarean Delivery may Increase Risk of Developing Crohn’s Disease

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A population-based study analysing over one million individuals suggests that babies born via caesarean section delivery may face a higher risk of developing Crohn’s disease later in life. The findings, published in Acta Obstetricia et Gynecologica Scandinavica, add to a growing body of evidence on long-term impacts of caesarean section delivery. 

More and more people are being delivered by caesarean section, and there is interest in understanding possible long-term health consequences of this mode of delivery. One possible route is through a lack of the early exposure of the infant to colonising bacteria via a vaginal delivery. Previous studies suggest that infants delivered by CS are at increased risks of disorders involving the immune system, such as asthma and allergies, type 1 diabetes, celiac disease, obesity, immune deficiencies, and leukaemia and other malignancies affecting young people.

In this study, all full-term individuals registered in the Medical Birth Register in Sweden between 1990 and 2000 were followed until 2017. Among 1 102 468 individuals, of whom 11.6% were delivered by caesarean section and 88.4% were vaginally delivered, caesarean section was associated with a 14% higher risk of developing Crohn’s disease after adjusting for confounding factors. No associations between delivery mode and appendicitis, ulcerative colitis, cholecystitis, or diverticulosis were found.

“Our study is the largest in this field, showing new interesting associations between caesarean section and increased risk later in life for Crohn’s disease. We hypothesise that the underlying mechanism could be the gut microbiome, but further studies will have to confirm this,” said senior author Anna Löf Granström, of the Karolinska Institute.

Source: Wiley

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Two New Antibody Treatments for Crohn’s Disease Equally Effective

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Anatomy of the gut
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In a clinical trial, two new antibody treatments for Crohn’s disease were approximately similar in effectiveness, according to findings published in The Lancet.

This allows clinicians and patients to make treatment choices based on tolerance, according to Stephen Hanauer, MD, the Clifford Joseph Barborka Professor and a co-author of the study.

“The safety and efficacy of two agents with different mechanisms of action appears to be quite comparable over one year,” said Prof Hanauer.

Crohn’s disease (CD) is a chronic, progressive inflammatory bowel disease, causing abdominal pain, weight loss and fatigue. Treatment has usually focused on alleviating symptoms to achieve clinical remission using corticosteroids or immunomodulators, but more effective treatment is still needed, according to Prof Hanauer.

‘While there are numerous therapies and mechanisms of action for drugs approved for moderate-severe Crohn’s disease there has been a therapeutic ceiling as far as outcomes are concerned, with usually less than 50% of patients in long-term remission,” Prof Hanauer explained.

Recently, several biologic agents have been approved for use. Adalimumab is a monoclonal antibody that reduces inflammatory cytokines by inhibiting tumor necrosis factor alpha. Ustekinumab is another monoclonal antibody, though the drug targets a different set of proteins: interleukin (IL) 12 and IL-23.

Researchers recruited with Crohn’s disease, randomising 191 to receive ustekinumab and 195 to adalimumab. Patients reaching clinical remission were similar between both groups: 65% of 191 patients in the ustekinumab group versus 61% of 195 in the adalimumab group. There were no deaths through one year of study, though slightly more patients in the ustekinumab group discontinued study treatment. Disease severity measures decreased similarly over the study.

Both treatment regimens resulted in clinical remission with similar toxicity profiles.

“There are numerous options for patients with moderate-severe disease. However, the key is to treat patients with an effective regimen and treat to targets as early in the course as possible since we do not have any drugs that impact on fibrosis once it occurs,” Prof Hanauer said.

Source: Northwestern University

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Growing up with Dogs (But not Cats) Protects Against Crohn’s Disease

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Young children who grow up with a dog or in a large family appears to confer some protection later on in life from Crohn’s disease, according to a study presented at Digestive Disease Week® (DDW) 2022.

Crohn’s disease is a common type of inflammatory bowel disease that often develops in young adults, smokers, and those with a close family member who has IBD. Symptoms include diarrhoea, abdominal pain and weight loss. Treatments currently aim to prevent symptom flare-ups through diet modification, medication, and surgery.

“Our study seems to add to others that have explored the ‘hygiene hypothesis’ which suggests that the lack of exposure to microbes early in life may lead to lack of immune regulation toward environmental microbes,” said Williams Turpin, PhD, the study’s senior author and a research associate with Mount Sinai Hospital and the University of Toronto.

Researchers used an environmental questionnaire to collect information from nearly 4300 first-degree relatives of people with Crohn’s disease enrolled in the Crohn’s and Colitis Canada Genetic, Environmental, and Microbial (CCC-GEM) project. Using responses to the questionnaire and historical data collected at the time of recruitment, Dr Turpin and his team analysed several environmental factors, including family size, the presence of dogs or cats as household pets, the number of bathrooms in the house, living on a farm, drinking unpasteurised milk and drinking well water. The analysis also included age at the time of exposure.

The study found that exposure to dogs, especially from ages 5 to 15, was associated with healthy gut permeability and balance between the microbes in the gut and the body’s immune response, which may all help protect against Crohn’s disease. Similar effects were observed with exposure to dogs across all age groups.

“We did not see the same results with cats, though we are still trying to determine why,” Dr Turpin said. “It could potentially be because dog owners get outside more often with their pets or live in areas with more green space, which has been shown previously to protect against Crohn’s.”

Another protective factor seemed to be living with three or more family members in the first year of life, which was associated with microbiome composition later in life. The gut microbiome is believed to play a role in a number of health conditions, such as inflammatory bowel disease, colorectal cancer, diabetes, and high blood pressure.

Dr Turpin and his colleagues hope their findings may assist physicians in asking detailed questions of patients to determine who is at highest risk. However, he noted that the early life environmental factors were assessed by questionnaires, so caution is warranted in interpreting these results due to possible recall bias at recruitment. The reasons dog ownership and larger families appear to provide protection from Crohn’s remain unclear.

Source: Digestive Disease Week

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A Fungus in Certain Foods Slows Intestinal Healing

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A study has found that a fungus found in certain foods such as cheese and processed meats can cause intestinal injuries in humans and mice with Crohn’s disease to fester and impeding healing.

These findings, from researchers at Washington University School of Medicine in St. Louis and the Cleveland Clinic, suggest that there is potentially a diet-based way to treat Crohn’s disease.

“We’re not suggesting that people stop eating cheese and processed meat; that would be going far beyond what we know right now,” said first author Umang Jain, PhD, an instructor in pathology & immunology at the School of Medicine. “What we know is that this foodborne fungus gets into inflamed, injured tissue and causes harm. We’re planning to perform a larger study in people to figure out if there’s a correlation between diet and the abundance of this fungus in the intestine. If so, it is possible dietary modulation could lower levels of the fungus and thereby reduce symptoms of Crohn’s disease.”

Crohn’s disease is driven by chronic inflammation in the gastrointestinal tract and immunosuppressive medication is the usual treatment. Crohn’s patients endure flare-ups where digestive tracts are dotted with inflamed, open sores that can persist for up to months.

To understand why intestinal ulcers heal so slowly in some people, the researchers studied mice with injured intestines. By sequencing microbial DNA at the site of injury, they discovered that the fungus Debaryomyces hansenii was abundant in wounds but not in uninjured parts of the intestine. D. hansenii can be found in all kinds of cheeses, as well as sausages, beer, wine and other fermented foods.

Introducing D. hansenii into mice with injured intestines slowed down the healing process, and eliminating the fungus with amphotericin B sped it up. In humans, the researchers discovered  D. hansenii in seven out of seven of people with Crohn’s disease, and another analysis of Crohn’s patients found D. hansenii present but only in sites of injury and inflammation. 

“If you look at stool samples from healthy people, this fungus is highly abundant,” Jain said. “It goes into your body and comes out again. But people with Crohn’s disease have a defect in the intestinal barrier that enables the fungus to get into the tissue and survive there. And then it makes itself at home in ulcers and sites of inflammation and prevents those areas from healing.”

Their results suggest that elimination of the fungus could allow wounds to heal normally again, and minimise flare-ups. In mouse studies, amphotericin B eliminated the fungus but it is of limited use in people since it can only be administered intravenously, therefore an oral antifungal is being researched.

“Crohn’s disease is fundamentally an inflammatory disease, so even if we figured out how to improve wound healing, we wouldn’t be curing the disease,” Jain said. “But in people with Crohn’s, impaired wound healing causes a lot of suffering. If we can show that depleting this fungus in people’s bodies—either by dietary changes or with antifungal medications—could improve wound healing, then it may affect the quality of life in ways that we’ve not been able to do with more traditional approaches.”

Source: Medical Xpress

Journal information: U. Jain et al., “Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice,” Science (2021). science.sciencemag.org/cgi/doi … 1126/science.abd0919