Research Reveals a Major Cause of Inflammatory Bowel Illness

The research demonstrates that inflammatory bowel disease and associated illnesses are brought on by a novel biochemical route.
An autoimmune disease like IBD, which includes ulcerative colitis and Crohn's disease, currently affects one in ten persons in the UK and about 5% of the global population. (Representational image: Wikimedia Commons)
An autoimmune disease like IBD, which includes ulcerative colitis and Crohn's disease, currently affects one in ten persons in the UK and about 5% of the global population. (Representational image: Wikimedia Commons)

A novel biochemical route that can be treated with current drugs has been found by researchers to be a primary cause of Inflammatory Bowel Disease (IBD) and associated illnesses.

An autoimmune disease like IBD, which includes ulcerative colitis and Crohn's disease, currently affects one in ten persons in the UK and about 5% of the global population. Additionally, the prevalence of these illnesses is rising; by 2022, over 500,000 people in the UK will have IBD, almost twice as many as the previous estimate of 300,000.

Despite the rising frequency, not all patients respond to current treatments, and efforts to create novel medications frequently fall short since we still don't fully understand the underlying causes of IBD.

Scientists at the Francis Crick Institute traveled into a "gene desert," which is a region of DNA that does not code for proteins and has previously been linked to IBD and several other autoimmune diseases. They conducted this research in collaboration with UCL and Imperial College London, and their findings were published in Nature.

Researchers discovered that within this gene desert is a region of DNA known as a 'enhancer,' which functions similarly to a volume dial for neighboring genes, increasing the production of proteins. The researchers found that this specific enhancer enhanced a gene called ETS2, whose levels are associated with an increased risk of disease. It was found that this enhancer was only active in macrophages, a kind of immune cell known to be crucial in IBD.

An autoimmune disease like IBD, which includes ulcerative colitis and Crohn's disease, currently affects one in ten persons in the UK and about 5% of the global population. (Representational image: Wikimedia Commons)
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The researchers demonstrated by genetic editing that ETS2 was required for nearly all inflammatory processes in macrophages, including a number of processes that directly result in tissue destruction in IBD. Remarkably, resting macrophages could be made into inflammatory cells that closely mirrored those from IBD patients by merely adding more ETS2.

After testing this, the researchers found that these medications decreased inflammation in both gut samples from IBD patients and macrophages.

It was found that this enhancer was only active in macrophages, a kind of immune cell known to be crucial in IBD. (Representational image: Unsplash)
It was found that this enhancer was only active in macrophages, a kind of immune cell known to be crucial in IBD. (Representational image: Unsplash)

The researchers are currently collaborating with LifeArc to develop strategies for delivering MEK inhibitors straight to macrophages because these drugs may cause adverse effects in other organs.

The research's principal investigator, James Lee, a consultant gastroenterologist at the Royal Free Hospital and UCL and group leader of the Genetic Mechanisms of Disease Laboratory at the Crick, stated: "IBD typically develops in young people and can cause severe symptoms that disrupt education, relationships, family life, and employment." We desperately need better remedies.

"We have discovered a pathway that seems to be important in IBD and other inflammatory illnesses, using genetics as a starting point. We've demonstrated that this can be targeted therapeutically, which is exciting, and we're currently working on ways to make sure this method is secure and useful for treating patients going forward."

James Lee, Consultant Gastroenterologist at the Royal Free Hospital and UCL, and Group Leader of the Genetic Mechanisms of Disease Laboratory at the Crick

"IBD and other autoimmune conditions are really complex, with multiple genetic and environmental risk factors, so to find one of the central pathways, and show how this can be switched off with an existing drug, is a massive step forwards," said Christina Stankey, a PhD candidate at the Crick Institute and the study's first author, along with Christophe Bourges and Lea-Maxie Haag.

An autoimmune disease like IBD, which includes ulcerative colitis and Crohn's disease, currently affects one in ten persons in the UK and about 5% of the global population. (Representational image: Wikimedia Commons)
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Blood samples from volunteers at the NIHR BioResource, both with and without IBD, were used in this study. Crohn's and Colitis UK, the Wellcome Trust, MRC, and Cancer Research UK provided funding for the study, and the researchers collaborated with partners around Europe and the UK.

"Inflammatory bowel disease affects over 25,000 people annually. Although there is no known cure for Crohn's or colitis, research like this is assisting in addressing some of the major problems regarding its etiology. The greater our comprehension of Inflammatory Bowel Disease, the more probable it is that we will be able to assist sufferers in leading fulfilling lives despite these ailments. This finding represents a very promising step toward the eventual elimination of Crohn's and colitis."
Ruth Wakeman, Director of Services, Advocacy, and Evidence at Crohn's & Colitis UK

In 2018, 27-year-old Lauren Golightly was diagnosed with Crohn's disease following symptoms of irregular bowel movements, blood in her stool, and stomach cramps.

"Crohn's has had a huge impact on my life," the woman stated. Since being diagnosed, I've had a difficult journey that has included numerous hospital stays, numerous prescriptions, and even surgery to get a temporary stoma bag. The uncertainty around Inflammatory Bowel Disease (IBD) is one of the most difficult aspects of the condition. I still get flare-ups and can be in the hospital for extended periods of time. Finding out about this research is really inspiring and thrilling. It is my hope that this may help myself and the hundreds of thousands of other people who are dealing with IBD.

(Input from various sources)

(Rehash/Priyanka Pandey/NJ)

An autoimmune disease like IBD, which includes ulcerative colitis and Crohn's disease, currently affects one in ten persons in the UK and about 5% of the global population. (Representational image: Wikimedia Commons)
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