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What is inflammatory bowel disease?

By: Paul Bertrand, Lu Liu
31 July, 2013

Inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine that can cause life-threatening complications and may require surgery.

Luckily, current therapies offer real benefits and there are some promising drugs in the pipeline.

The disease is one of a variety of unrelated but ongoing gastrointestinal disorders. Of these, some of the most common complaints are about gluten intolerance and functional bowel problems (when the gut doesn't work properly, such as when someone has irritable bowel syndrome). Crohn's disease and ulcerative colitis are examples of inflammatory bowel disease.

All of these problems have very different causes, although having one of them may put you at an increased risk of developing another.

Causes and effects

The precise causes of inflammatory bowel disease are not known. What we do know is that, in general, people with inflammatory bowel disease are likely to have a genetic predisposition for the disease. Their genes make it more likely that they will develop inflammatory bowel disease although they may never do so.

If they develop the disease, it's most likely because of an environmental trigger – stress, for instance, or malnutrition or certain drugs. But, in most people, the trigger may never be known.

Factors in the gut, such as a disruption in the balance between good and bad bacteria, can also contribute to the onset of the disease.

The effect of inflammatory bowel disease on the gut is actually caused by the person's immune system. Once activated, the disease attacks the body's cells instead of foreign cells such as bacteria, fungi or viruses.

This initiates the sort of angry red inflammation in the gut that would normally get rid of infections. Unfortunately, in the case of inflammatory bowel disease, the immune system reacts to bacteria that are normally resident in the gut. And, in so doing, the disease causes severe damage that can cause a perforation (a hole through the wall of the gut).

This is a life-threatening event and, at this point, surgery is the only treatment option. The many surgeries some people suffering from inflammatory bowel disease have to undergo during their life is extremely burdensome.

But there's an indirect benefit for the community in this – the resulting surgical samples can sometimes be used to help researchers who are trying to find a cure for inflammatory bowel disease.

Current and new treatments

Inflammatory bowel disease is not active all the time – it is prone to flare-ups that are separated by quiet times during which the disease is in remission. This makes treatment more complicated because it can be hard to know if the remission is caused by a new drug or if it's spontaneous.

Most cases of inflammatory bowel disease are initially handled by giving the sufferer an anti-inflammatory drug that will hopefully induce remission. Once in remission, many patients take immunosuppressant drugs that decrease the likelihood of another flare-up.

Immunosuppressants are drugs that modify how the immune system works and generally lower its activity. Many new drugs that fall into this general class are being developed.

With the immune attack reduced, the gut can often heal on its own and stay healthy for longer. Current treatment strategies generally start with older drugs but if these fail, biological therapies, such as infliximab, are tried. A biological therapy also targets the immune system. The active compounds often originate from human, animal or bacterial sources – for example, infliximab is an antibody.

These drugs are effective in many people but they can have severe side-effects and become less effective over time.

Three new such drugs (all using the same approach) are currently undergoing the lengthy regulatory approval process overseas. They inhibit a protein in the body called an "integrin", which helps cells stick together. In inflammatory bowel disease, the integrins are what allow immune cells to invade the intestine and start the inflammatory process.

The role of integrins has been known for many years, but the problem is that they are located everywhere in the body. Drugs that block all integrins are dangerous for various reasons, for example, because blood clotting is dependent on integrins.

These new drugs block only one specific type of integrin and seem to be safe and effective. They target a kind of integrin that is only found on some white blood cells that are crucial for an immune response in inflammatory bowel disease.

To date, these drugs have been mainly tested on patients who have already failed using current therapies. There's hope that once these drugs are registered, they will find an earlier use in less severely affected patients.

It's likely that one or more of these new drugs will get regulatory approval before long, but it may be another four or five years before they would be prescribed to patients. Clinical trials to monitor their safety and effectiveness will be required first.

Paul Bertrand receives funding from National Health and Medical Research council for projects relating to gastrointestinal health.

Lu Liu receives funding from National Health and Medical Research Council.

This article was first published at The Conversation.

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