Major cause of inflammatory bowel disease discovered

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IBD), shedding light on the complex mechanisms underlying this chronic condition. IBD, which includes Crohn's disease and ulcerative colitis, affects millions of individuals worldwide and is characterized by inflammation in the gastrointestinal tract.

The discovery of a specific type of gut bacteria, known as adherent-invasive Escherichia coli (AIEC), has been found to play a significant role in triggering and perpetuating inflammation in individuals with IBD. These bacteria are able to adhere to and invade the intestinal lining, leading to an abnormal immune response and chronic inflammation.

An autoimmune disease, such as IBD, which encompasses Crohn's disease and ulcerative colitis, presently affects approximately 5% of the world's population. One part of the immune system that is highly implicated in IBD is white blood cells called macrophages. These flood the linings of the intestines where they release chemicals causing massive inflammation.

Inflammation is part of the body's normal response to infection, but too much for too long can have devastating health consequences. 

DNA that is present in 95 per cent of people with the disease, making it easier for some immune cells to crank up the amount of proteins they make, resulting in inflammation in the bowels.

Lee’s research team “stumbled” on the discovery after investigating a “gene desert”, a stretch of DNA on chromosome 21 that does not code for proteins, which has previously been linked to IBD and other autoimmune diseases. Writing in Nature, they describe how they found a section of DNA that behaves like a volume control for nearby genes. This “enhancer” was seen only in immune cells called macrophages where it boosted a gene called ETS2 and ramped up the risk of IBD.

IBD.

Christina Stankey, a PhD student at the Crick and co-first author, says: “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 forward.”

As MEK inhibitors can have side effects in other organs, the researchers are now working to find ways to deliver them directly to macrophages.

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