Inflammatory Bowel Disease: Chronic Inflammation Can Cause Divergent Evolution in Colon Cells

by Danielle Bradshaw from In The Cloud Copy

Healthy and diseased colon cells were collected and compared to each other in a recent study to discover why inflammatory bowel disease can lead to a higher chance of developing colorectal cancer down to the molecular level.
During the study, the Cambridge University Hospital and Wellcome Sanger Institute teams discovered that DNA within IBD colon cells change at a faster rate (more than double) than cells inside a healthy colon. The accelerated rate of change has been found to heighten the chance of these unhealthy cells undergoing transformations in their DNA that could potentially lead to cancers.

The study (which was published in Cell) has also found that the colon’s structural integrity is disturbed by the chronic inflammation that comes with having IBD and this helps to distribute cells across an irregularly large area. All in all, this study into colon cells has provided tremendous insight into the effects of IBD on colorectal cancers and the body itself.

What Is Inflammatory Bowel Disease?

Inflammatory bowel disease, in reality, refers to diseases (Crohn’s disease and ulcerative colitis) where digestive system inflammation is a major symptom. From 1990 to 2017, around 6.8 million people have been diagnosed with IBD. Although scientists and researchers haven’t figured out precisely what causes the illness, it’s believed that the intestinal inflammation is caused by the immune system reacting negatively to a person’s gut microbes.
People that have some form of IBD have a higher chance of developing gastrointestinal cancers as opposed to other people which is just one reason why treatment is important. Sufferers of IBD will need to be monitored regularly to decrease the chances of this occurring and may even need (or want) to have their entire colon removed to lower the risk.

The Study Process and Procedures

To perform the study, Addenbrooke’s Hospital medical staff gathered colon tissue samples from 46 of their IBD patients as well as their (anonymous) medical and treatment history. The Wellcome Sanger Institute researchers took the samples and cut out 446 separate intestinal crypts (small pockets that together form the colon’s tissue – it’s where stem cells for intestinal epithelium regeneration are stored) so that they could whole-genome sequence – figure out the complete DNA sequence of the tissue in one go – the samples.

Once sequenced, the samples were then looked over so that the team of researchers could figure out how fast the tissue’s DNA would change, what the genetic relationship among crypts are, and if there were any genes that were abnormally mutated. The team then took these same tissue samples and correlated to sequences from 41 people without IBD (these samples were separated into 412 separate crypts) so that they could clearly see how the chronic inflammation affected the DNA.

Results of the Study

After the study was completed, it was discovered that the IBD colon tissue DNA had changed twice over as opposed to what could be found in non-diseased tissue. They also discovered that the longer the person had the disease, the more chances that they were able to observe transformation.

It was also found that there was an evolutionary process of sorts where some gene mutations were positively-selected and that some of these mutations are augmented inside of genes that are connected to colon cancer. The observation of this process has provided some much-needed information on the relation between some cancers and IBD. This research has also provided proof that the positive selection of mutations within immune system regulation genes and in the colon’s cells capacity to stave off the bacteria inside it does, in fact, occur.

Before this study was done, there was no explanation for the fact that in some IBD flare-ups, the same bit of tissue usually ended up being inflamed. It was thought that this was the result of permanent changes within the colon. These results seem to indicate, however, that genetic mutations may be the culprit. It seems as though certain positively-selected mutations inside of genes in charge of immune regulation occur in the same parts of the bowel that are impacted by inflammation.

Dr. Carl Anderson (the lead author of the Wellcome Sanger Institute’s study) says that while it was already known that changes to the DNA can cause cancer to appear, they weren’t sure how it connected to diseases like IBD. He says that their study showed that the changes inside the cells that line the gut are possibly linked to the appearance of IBD. The study of mutations inside of diseases can help us better understand the biology of diseases and pinpoint possible drug targets.

Check out the original article here.

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