GASTRIC GOLD'S BLOG

Scientists at The University of Nottingham are investigating whether stem cell markers could have a role to play in speeding up wound healing in patients suffering from inflammatory bowel disease (IBD).

The study could eventually lead to the development of new drugs which use natural molecules to spark the recovery of patients suffering from ulcerative colitis and Crohn's disease, reducing their risk of associated complications such as scarring, bowel obstructions and tumour growth.

Funded with a £118,500 grant from the National Association for Colitis and Crohn's Disease (NACC), the two-year project is being led by Professor Mohammad Ilyas in the University's Division of Pathology.

He said: "The study will focus on the molecule CD24 which is a stem cell marker and which plays a key role in cell proliferation and the migration of healthy cells to a damaged area to restore normal tissue.

"CD24 is a small molecule attached to the cell membrane which has been recently reported as a marker of stem cells in the colon. It occurred to us that CD24 might have a role to play in IBD and during further studies we found that it was indeed present in sections of diseased bowel."

IBD affects around one in 400 people in the UK. Common symptoms include inflammation and ulceration of the intestine and colon, pain, severe diarrhoea, tiredness and weight loss. The cause of the disease is yet to be definitively identified, although scientists believe it could be due to a combination of genetic predisposition and environmental factors. Currently, there is no cure and patients manage their condition with a mixture of lifestyle changes, anti-inflammatory drugs and, in severe cases, surgery.

Professor Ilyas added: "The power of the gut to heal the damage caused by acute episodes of inflammation is remarkable and frequently the gut lining reverts to normal. Anti-inflammatory drugs help this process along and allow the wound healing to begin earlier than it would naturally.

"In the future, it may be possible to use a variety of therapies (possibly including gene therapy) to manipulate the expression of the CD24 molecules on cells to promote even more rapid healing. This may mean less scarring, bowel obstruction and fistulation and less chance of developing tumours resulting from persistent inflammation. As a result of this, it may also reduce the chance of needing surgery further down the line."

In the early stages of the project, the pathologists will be using cell lines in the lab to study CD24 at a cellular and molecular level to discover the mechanisms by which it operates and encourages cell migration and other associated molecules that are co-expressed.

They will then examine diseased IBD tissue to establish whether what they have observed in the lab is occurring in reality.

It is hoped the findings will lead to further clinical work to look at the possible benefits of CD24 in allowing IBD patients to more effectively manage their disease.

The CEO of NACC, Richard Driscoll, explains, "Since 1984, NACC members have raised over £4.5 million and more than 100 research awards have been made to hospitals and universities throughout the United Kingdom. This year our Medical Research Committee selected three studies to receive NACC research awards which we hope will contribute to finding improved treatments and ultimately a cure for IBD. We welcome Professor Ilyas' work on CD24 in seeking a better understanding of the gut healing process and how it may be enhanced in inflammatory bowel disease."

Source:
Professor Mohammad Ilyas
University of Nottingham

Labels: IBD, IBS, Inflamatory Bowel Disorders, Irritable Bowel Syndrome

Bacteria naturally present in the human gut could produce substances that help to protect against colon cancer and provide therapy for inflammatory bowel disease. In a paper published in the journal Microbiology, researchers from the University of Aberdeen Rowett Institute of Nutrition and Health and from the MTT Agrifood Research Institute in Finland report initial studies showing that bacteria in the human gut convert linoleic acid, a naturally-occurring fat in the diet, into a form called conjugated linoleic acid (CLA) which is absorbed by the gut wall.

There are different types of CLA and not all of them have beneficial effects. The "good" form of CLA is present in dairy foods such as milk and cheese," said Dr John Wallace of the Rowett Research Institute, "but eating lots of dairy foods won't necessarily help our gut health as most of the fats are digested in the small intestine before they get to the large intestine, where most of our gut bacteria are found." The results of these latest studies showed that several different forms of CLA are produced by gut bacteria. Fortunately, most was of the "good" kind, but Dr Wallace stressed that more extensive studies are needed. One subject produced small amounts of a CLA whose beneficial or otherwise effects are much less clear.

The implications are that, if small quantities of dietary linoleic acid can be delivered to the large intestine, the effects on gut health will be generally beneficial in most people. He added, "The results are of special interest for individuals using anti-obesity treatments that prevent the small intestine from absorbing fats. This means that those fats - including linoleic acid - will pass into the large intestine and the gut bacteria will produce CLA. It has to be the correct CLA, so it is important to understand how individuals produce different CLA. This must depend on which types of bacteria are present."

Labels: Cancer, IBD, Inflamatory Bowel Disorders, Irritable Bowel Syndrome

Scientists have uncovered vital clues about how to treat serious bowel disorders by studying the behaviour of cells in the colon.

Researchers at the University of Edinburgh believe a chemical messenger that is essential for developing a baby's gut in the womb could hold the key to new treatments for inflammatory bowel disease (IBD), a condition which affects 1 in 250 people in the UK.

The team studied a chain of chemical reactions inside colon cells, called the Hedgehog signalling pathway, which controls the way it behaves and communicates with other cells.

The researchers found that some patients with IBD inherit a defective copy of one of the important links in this chain, a gene called GLI1. This defective GLI1 is only half as active as normal. Additionally, the Hedgehog pathway itself signals at lower levels than normal when the large bowel is inflamed.

The results suggest that the GLI1 protein may calm inflammation within the healthy colon, and that this process appears to go wrong in IBD patients, causing their gut to become inflamed.

The researchers now hope to test whether strengthening this weakened protein will help to prevent or treat inflammatory bowel diseases like Crohn's disease and ulcerative colitis.

Dr Charlie Lees from the University's Institute of Genetics and Molecular Medicine, who led the study, said: "Everybody has billions of bacteria in the gut, the vast majority of which do us no harm. Our body's natural immune responses identify and eliminate harmful bacteria, whilst living in harmony with the healthy bacteria. But in people with inflammatory bowel disease, that response goes wrong and an over-active immune response against these healthy bacteria leads to chronic inflammation in the gut.

"It now seems that the Hedgehog signalling pathway, and specifically the GLI1 protein, is crucial to that response. We think it provides an important signal to certain types of immune cells in the gut wall, instructing them to adopt an anti-inflammatory state. If we can find ways to bolster these responses in people with IBD, we may be able to help prevent the painful attacks which are so devastating to patients."

Labels: IBD, Inflamatory Bowel Disorders