Exploring the epigenetic changes in diverticular sepsis vs 1
Research type
Research Study
Full title
Exploring the epigenetic changes in diverticular sepsis (Explodes study)
IRAS ID
277920
Contact name
Frank McDermott
Contact email
Sponsor organisation
RD&E NHS FT
Clinicaltrials.gov Identifier
277920, IRAS
Duration of Study in the UK
0 years, 11 months, 31 days
Research summary
Research Summary:
Diverticular disease is common and caused by small pouches in the large bowel that can bleed or become inflamed (diverticulitis). Some patients need simple treatments, while others may develop severe infection (sepsis) leading to emergency surgery; currently this is difficult to predict.
We want to take a new approach and look at how environment (e.g. ageing, smoking and diet) may cause small changes to how our genes (DNA) work (epigenetics). By looking for epigenetic changes in blood samples from patients admitted with either mild diverticulitis or complicated perforated disease, and comparing them with those from healthy individuals, we hope to understand more about their impact on diverticular disease, and explain why some patients get mild disease and others life threatening sepsis.
To do this we will collect a one off blood sample from patients admitted with either mild or complicated diverticulitis. This will taken as soon as possible after admission (it may be possible to take the extra sample at the time a routine sample is being taken). When this sample has been taken participants will have no further active part to play in the study. Healthy age and sex matched controls will be identified from existing research databases who have given permission to be contacted about further research. Samples will be used to explore epigenetic changes between groups.While we cannot change our DNA code (this is passed down from our parents) epigenetics looks at how small changes can alter how our genes work (e.g. switching them on and off). These changes can be reversed, so this research could be a first stage in helping identify patients with higher risk of sepsis, leading to earlier interventions and improved clinical outcomes.
Summary of Results:
Diverticular disease is a common condition where small pockets develop in the bowel wall. Sometimes, these can become infected or burst, leading to serious complications such as sepsis. Doctors currently have limited tools to predict who will become seriously unwell from this disease.
The EXPLODES study looked at how certain changes in a person’s DNA—known as epigenetic changes—might help us better understand and predict how severe someone’s illness will be. These changes don’t affect the DNA code itself, but how genes are switched on or off, and they can be influenced by illness or inflammation.
Researchers collected blood samples from patients admitted to hospital with diverticulitis (an infection or inflammation of diverticular disease) and compared them with healthy volunteers. The study used advanced technology to examine over 850,000 markers across the DNA of each participant.
They found differences in DNA markers between people with mild and severe diverticulitis. Some of these changes were in genes involved in the body’s immune system and in how nerves and muscles work in the gut. These findings suggest that epigenetic changes might play a role in how the disease develops and how severely it affects people.
This is the first study to show that DNA methylation—an important type of epigenetic change—is linked to diverticular sepsis. The results are promising and could one day help doctors predict which patients are most at risk of serious complications, allowing for better and more personalised treatment.
REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
20/YH/0078
Date of REC Opinion
17 Mar 2020
REC opinion
Favourable Opinion