Inflammatory bowel disease: 'Major cause of IBD' discovered by researchers

FILE - An illustration of Crohns Disease (Photo By BSIP/UIG Via Getty Images)

About 5% of the world’s population, including an estimated 3.1 million adults in the U.S., suffer from inflammatory bowel disease (IBD) – the umbrella term for Crohn’s disease and ulcerative colitis.

People with IBD are more likely to have other chronic conditions and sleep less than 7 hours a day, according to the U.S. Centers for Disease Control and Prevention. Common symptoms can include abdominal pain, diarrhea (sometimes with blood), urgency to have a bowel movement, rectal bleeding, weight loss, fever, anemia, and even anxiety and depression.

Researchers say IBD cases have also become more common in recent years.

But despite its increasing prevalence, researchers say current treatments don’t work in every patient, and attempts to develop new drugs often fail due to an incomplete understanding of what causes the disease. 

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New research published this week in the journal Nature identifies a "major genetic driver" for IBD and related conditions, and suggests it can be targeted using existing drugs.

IBD breakthrough

A team of researchers at London’s Francis Crick Institute, working with University College London and Imperial College London, focused their research on a "gene desert" – or an area of DNA that doesn’t code for proteins – which has previously been linked to IBD and several other autoimmune diseases.

The team found that this particular gene desert contains an "enhancer," or a section of DNA that is like a volume dial for nearby genes – able to crank up the amount of proteins they make, according to a press release about the study.  

Researchers discovered that this particular enhancer was only active in macrophages, which are a type of immune cell known to be important in IBD, and boosted a gene called ETS2, with higher levels correlating with a higher risk of disease.  

Using genetic editing, the scientists showed that ETS2 "was essential for almost all inflammatory functions in macrophages, including several that directly contribute to tissue damage in IBD." 

"Strikingly, simply increasing the amount of ETS2 in resting macrophages turned them into inflammatory cells that closely resembled those from IBD patients," the release noted. 

The researchers also found that many other genes previously linked to IBD are part of the ETS2 pathway, "providing further evidence that it is a major cause of IBD."

ETS2 as a target for treatment

Specific drugs that block ETS2 don’t exist, according to the study authors, so the team searched for drugs that might indirectly reduce its activity. 

They found that MEK inhibitors, which are drugs already prescribed for other non-inflammatory conditions, were predicted to switch off the inflammatory effects of ETS2.

The team put this to the test and discovered that these drugs both reduced inflammation in macrophages, and also in gut samples from patients with IBD.

MEK inhibitors can have side effects on other organs, according to the team, which noted how they are now working with the medical research charity LifeArc to find ways to deliver MEK inhibitors directly to macrophages.

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Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are two different gastrointestinal disorders, though the differences between the two can be confusing.

They can have some similar symptoms, according to the Crohn's & Colitis Foundation, but IBS and IBD are not the same condition and require very different treatments. 

IBD, classified as a disease, can cause destructive inflammation and permanent harm to the intestines. IBS, on the other hand, is classified as a syndrome and does not cause inflammation nor rarely requires hospitalization or surgery.

IBD can bring an increased risk of colon cancer, while IBS does not. 

IBS can cause a great deal of discomfort and can severely affect a person’s quality of life with symptoms ranging from "mildly annoying to disabling," the foundation says.

Symptoms often occur after eating a large meal or when a person is stressed and can be temporarily relieved by having a bowel movement, the foundation adds.

This story was reported from Cincinnati.