Major cause of inflammatory bowel disease discovered

New pathway discovered as major cause of IBD, offering hope for improved treatments with existing medications.

Researchers have identified a new biochemical pathway that is a major cause of inflammatory bowel disease (IBD) and related disorders that can be addressed with existing medications.

An autoimmune disease, such as IBD, which encompasses Crohn’s disease and ulcerative colitis, presently affects approximately 5% of the world’s population and one in every 10 people in the United Kingdom. These diseases are also becoming increasingly widespread, with over half a million individuals in the UK living with IBD by 2022, nearly double the previous prediction of 300,000.

Despite increasing prevalence, current treatments do not work in every patient and attempts to develop new drugs often fail due to our incomplete understanding of what causes IBD.

Researchers at Francis Crick Institute, in collaboration with UCL and Imperial College London published their findings in Nature. Scientists at the Crick journeyed into a ‘gene desert’ - an area of DNA that doesn’t code for proteins - which has previously been linked to IBD and several other autoimmune diseases.

They found that this gene desert contains an ‘enhancer’, a section of DNA that is like a volume dial for nearby genes, able to crank up the amount of proteins they make. The team discovered that this particular enhancer was only active in macrophages, 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 team also discovered 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.