Inflammatory bowel disease consists of two related diseases: ulcerative colitis and Crohn’s disease. In ulcerative colitis, the lining of the large intestine is inflamed, and in Crohn’s disease, the lining of the small or large intestine or both are inflamed. Typical symptoms include diarrhoea, crampy abdominal pain, passage of mucus (slime) and blood in the faeces. Crohn’s disease may be associated with fistula which are false connections between the intestine and skin, vagina, and bladder or other internal organs. Often there is general deterioration in health with poor appetite and loss of weight. About 1 in 300 people have inflammatory bowel disease and there is a tendency for the disease to run in families. It is a disease of affluence and so is relatively high in Australia and New Zealand compared to other countries, and is expected to increase countries such as China and India as their standard of living improves.
Inflammatory bowel disease is fundamentally an abnormal immune reaction of the intestine to the healthy normal bacteria in the intestines. The immune system in the intestine becomes activated and causes intestinal damage for reasons which are unclear but which the Department of Gastroenterology & Hepatology at TQEH are actively researching. 20% of those who suffer from inflammatory bowel disease experience onset in their teenage years before 20 years of age. It peaks in people in their 30s and 40s, and there is further small peak in the elderly. It affects people principally of child bearing age at their most productive stage of their life but also the young and old. Thus, it has major economic effects. Once inflammatory bowel disease commences, the tendency is for it to continue and to recur if treatment is interrupted.
A recent survey by the Australian Crohn’s and Colitis Association found that three-quarters of inflammatory bowel disease patients had to change their work duties, one-quarter of patients lost wages in the last 12 months, two-thirds had their education affected, two-thirds had to alter their travel plans and about half had one to three flares per year. It is more common than epilepsy, multiple sclerosis, rheumatoid arthritis or schizophrenia.
Inflammatory bowel disease is predisposed by a combination of multiple genes (more than 30) and environmental factors. These environmental factors include, use of frequent antibiotics during childhood which increases risk of developing inflammatory bowel disease, bacteria in the intestine, whether breast-fed which tends to protect or not and smoking which makes Crohn’s disease much worse.
Investigations of invariant NKT cells and T regulatory cells in IBD
A/Professor Adrian Cummins and co-workers from the Gastroenterology & Hepatology Department have established that there is a deficiency of an immunoregulatory cell called the invariant NKT cell in both Crohn’s disease and ulcerative colitis. The suggestion, which is still unproven, is that after one or more viral infections, the lack of these cells prevents the immune system in the intestine returning back to normal. This work was funded by the prestigious Broad Medical Research Program in the USA. Further work investigated another immune cell called the T regulatory cell. These were not found to be deficient but there was a more complex conversion of these T regulatory cells to TH17 inflammatory cells. It is hoped to continue these studies when more funding becomes available, but in the meantime, two scientists were awarded PhDs based on the first study over 7 years and the second study over 4 years at TQEH.
Present research is being undertaken to investigate which immune chemicals called cytokines are present and which immune cells produce these cytokines in the intestine, as there are up to 35 known cytokines and only a few have been investigated in inflammatory bowel disease. Some are damaging and pro-inflammatory while others are immunosuppressive and protective. Subjects are being recruited before treatment, which might otherwise alter the results. A doctor who has just finished his training as a specialist gastroenterologist is undertaking these studies for a research PhD.
Changes of bacteria in the intestine in inflammatory bowel disease
Research is also being undertaken of any change in bacteria in the large intestine in ulcerative colitis. This work is being done by Professor Ian Roberts-Thomson from TQEH in collaboration with workers at the CSIRO in Adelaide. As bacteria are thought to be the immune stimulus for inflammatory bowel disease, the question arises are they promoting damaging inflammation or just reacting to it?
Although mothers to be are often concerned about taking medical drugs that could potentially harm their baby, the general rule is to continue treatment of IBD except for taking methotrexate. It has been very difficult to find any increased risk of drugs used to treat inflammatory bowel disease but what is certain is that a relapse of inflammatory bowel disease during pregnancy is harmful to a baby with increased risk of miscarriage or earlier pre-term birth. Fortunately, inflammatory bowel disease mostly improves during pregnancy, but unfortunately comes back soon after birth, especially if treatment has been stopped.
Australian Crohn’s and Colitis Association: http://www.acca.net.au/
Broad Medical Research Program: http://www.broadmedical.org/
Crohn’s & Colitis Foundation of America: http://www.ccfa.org/