What switches genes on and off?

What is this research looking at? 

Over the last few decades there has been a steady increase in the number of children diagnosed with Crohn’s and Colitis.  This increase is most noticeable in ‘western’ countries, although it is now occurring in developing countries. In particular it has been noted in countries which are more rapidly adopting a ‘western’ lifestyle and diet.  It is thought that this is not just due to genetic factors. There must be environmental and lifestyles factors involved that are affecting the way genes are turned on and off.  The inner lining of the gut is the largest organ in the human body to be exposed to the environment. So the researchers wanted to look at the genes and how they work in the cells that line the gut (the epithelial cells). 

In particular, the researchers looked at epigenetic mechanisms. These are biological mechanisms that can switch genes on or off in body cells.  Changes to diet, the processing of food, and toxins have all been shown to affect epigenetics.  The researchers looked at an epigenetic mechanism called ‘DNA methylation’.  In DNA methylation, a chemical called a methyl group is added to the DNA. This then turns off the genes in that section of the DNA.  

To do this they took samples of epithelial cells from different places in the small and large bowel. They compared samples from children with a diagnosis of Crohn’s or Colitis with samples from children with no gut inflammation.

Conclusions

The research found that there were changes in DNA methylation in children newly diagnosed with Crohn’s or Colitis compared with children without Crohn’s or Colitis.  In Crohn’s disease these changes were seen in both the small bowel and the large bowel. In children with Colitis these changes were only seen in the large bowel. This may provide a way of being able to distinguish between Crohn’s and Colitis in people with an unclear diagnosis (or unclassified Inflammatory Bowel Disease). The researchers also found that there was a relationship between the DNA methylation profiles and certain disease outcome measures, including the need for treatment with biologics.

What do researchers think this could mean for people with IBD?  

This research shows that stable, non-genetic changes in the lining of the gut in children with Crohn’s or Colitis can contribute towards chronic inflammation. This is important because these changes, as they are not genetic, could potentially be reversed. This may be a focus for the development of new treatments for Crohns and Colitis.

These changes may be able to help distinguish between Crohn’s disease and Colitis in people with unclassified IBD. This could lead to a quicker and more accurate diagnosis for these people and more targeted treatment.

These changes may also be able to predict certain disease outcomes. This may allow for more individually targeted management of Crohn’s and Colitis.

This research was only done in a small number of children, and further research is being done to confirm the findings.

This research has been published and can be found at Howell et al, 2018 (free text)

Who is leading this research? Dr Matthias Zilbauer, University of Cambridge 
Project cost: £115,701
Duration: 24 months
Official title of application: Epigenetics in Paediatric IBD role as a clinical biomarker