Looking at the role of micro-RNA in Crohn’s and Colitis

This research will support the development of a blood-based biomarker to help predict which patients with Crohn's or Colitis may go on to develop more severe disease.


Professor Jack Satsangi, University of Oxford Dr Rahul Kalla, University of Edinburgh

What is this research looking at? 

Over the last 20 years there has been great progress in our understanding of the genes associated with Crohn’s Disease and Ulcerative Colitis. However, we still don’t know why some people develop Crohn’s and Colitis, while other people with the same genes do not. Both genes and environmental factors, such as smoking, diet and lifestyle, are believed to play a role in the development of Crohn’s and Colitis.  
Epigenetics is the study of biological mechanisms that change the way genes are switched on or off – and these changes can be triggered by environmental factors. MicroRNAs (miRNAs) are small strands of molecules that can switch genes on or off. miRNAs in the body can be influenced by things in the environment – research has already shown that changes to the bacteria in the gut can change the amount of miRNAs. Also, miRNAs derived from food have been found in the blood – and these miRNAs may also act in the body to switch genes on or off. People with different health conditions have different levels of certain miRNAs in their blood, so scientists think looking for these miRNAs in a blood sample could be used to diagnose or monitor health conditions. 
 
This study aimed to look for miRNAs in the blood of people with Crohn’s and Colitis and see if miRNAs are associated with markers of more severe disease, such as needing stronger treatments. 
  

What the researchers found 

Professor Satsangi and his team looked for miRNAs in a type of immune cell called CD8 T cells. Certain miRNAs were found at higher levels in CD8 T cells from people with newly diagnosed Crohn’s or Colitis than in CD8 T cells from healthy people. This is the first time these miRNAs have been found in people with Crohn’s or Colitis. Further analysis revealed that one of these miRNAs, called miR-1307-3p, could play a role in controlling inflammation in disease. 
 
At follow up, some of the newly diagnosed people with Crohn’s and Colitis went on to need stronger medicines or surgery. Having higher levels of certain miRNAs in the blood was able predict who would go on to need stronger medicines or surgery. Combining these miRNAs with currently available blood tests improved their ability to predict future disease severity. 
  

What do researchers think this could mean for people with Crohn's and Colitis? 

The researchers hope these results will lead to the development of a simple blood test to look for miRNAs in people with Crohn’s or Colitis. This blood test would be used to identify whether a newly diagnosed patient may go on to develop more severe disease and eventually need stronger medicines or surgery. Knowing this information at an early stage will allow doctors to better tailor treatment options and try to prevent long-term complications. 

This study also found that certain miRNAs can control disease-related inflammation –  providing new avenues for researchers to explore and the potential to develop new miRNA-based medicines to treat Crohn’s and Colitis.
 

Who is leading this research? Professor Jack Satsangi, University of Oxford
Our Funding: £100,089
Duration: 24 months
Official title of application: MicroRNA profiling in Inflammatory Bowel Diseases: The application of Next Generation Sequencing
Tags: Genetics 

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