Imagining IBD
This is a summary of the talk given by Dr. David Israel at the April CSIR/CCFC meeting, an evening shared with Dr. Steven Arvidson (naturopathic physician). It draws a comparison between the inflammation process of IBD and active law enforcement within a community.
Inflammatory bowel diseases are chronic conditions with no known cause or cure. The changes in the GI system may trigger several different symptoms that are not specific to IBD, but rather a reflection of changes in bowel function. Abdominal pain, diarrhea, and nausea are common side effects of many conditions, including IBD, and therefore manifestations of these symptoms in themselves are of limited value o our understanding IBD. Of course, the symptoms are very important to the patients as they may be incapacitating, preventing them from eating, limiting their activity and occasionally, confining them to bed.
Many patients will try any and all possible remedies to get better. Most will visit a medical doctor routinely, but as many as 50-70% will seek help from alternative medicine, usually without informing their doctor. Dietary manipulations are common, as are herbal preparations, and a naturopathic approach.
At the heart of INS is the inflammatory process. Inflammation is normal and important event in our body, but in IBD there is an exaggerated or poorly controlled response of the immune system. The immune systems acts as a special task force – like the police. These special police will control entry into the “community” and will identify intruders and outlaws. Anything that is not “by the book”, is quickly and efficiently isolated, or simply eliminated.
What valuable serves should a police force proved to a community? They administer a set of rules approved by the community and this can include:
- the identification of community members to ensure the rules are being followed,
- having the authority to deal with intruders and rule-breakers with the amount of force the community gives them, and
- the power to call in reinforcements when necessary.
The community determined the value system the police must follow, and therefore police forces vary greatly from community to community (as immune systems differ from person to person).
How does this translate to the function of the bowel during and inflammatory process?
Imagine the gut wall as an international border. There are different physical walls and obstacles to defend the boarders against invasion by bacteria, food products, drugs, and other materials. There are a few police members on routine patrol to remove uninvited intruders. Members of the police force have a keen memory and they usually can quickly differentiate between the good and the bad guys. They will provide safe passage for food (a good guy) but not for certain bacteria (previously identified as a bad guy).
The bowel uses special signals to call for reinforcement from remote places in the body to come and help when it is in a crisis. Different messages (or calls for help) will raise different kinds of assistance, depending on the situation. Once a crisis is over, there is a resolution process for the extra forces to go back to their remote bases in the body, leaving only the few original guards behind.
For this intricate plan to work properly, this police system has to be very sophisticated and follow strict procedures. Several different events can start the ball rolling and the police follow procedures that govern their response to any specific problem. It is crucial that the police never attack the community’s own good citizens. All member of the community are required to carry ID cards so that the Patrol officers can quickly verify friend or foe. For the safety of the community, the security system should be tamper proof and self-correcting. In the bowel this means that food is allowed to pass safely, but the actions of toxins and bacteria are restricted. What happens when the complicated system fails, and the usually efficient ID card system no longer separates the good form the bad?
On some occasions in a community, a need for help arises. Who remembers a riot that broke out in the usually peaceful downtown of Vancouver after a certain hockey game? What did the police do? They called in reinforcements from other communities to help with the crisis. When the situation was resolve, the reinforcements went back to their own communities.
The police must act quickly and close off approaches to the community and seal off a few blocks to contain the problem. This way, no new aggravation is introduced and things can settle down. But, if the streets stay closed for a longer time, public transportation, food supplies, and garbage removal are all interrupted. While a blockade can work to our temporary advantage, it can also create serious long term problems if allowed to continue.
The riot police can decide to use tear gas, pepper spray, water hoses or real deadly ammunition, depending on the situation. It is good to know that all this weaponry is available to the police, but there is a fear that innocent parties may be in the “war zone”. However, if the good and the bad cannot be distinguished from each other, we are in trouble. In the gut, assault with such powerful weapons can lead to swelling, poor food absorption, and changes in motility. Fever, diarrhea and nausea are also caused by the release of such weapons. Blood in the stool is a result of the destruction they can cause.
Factors such as the techniques the police use, how fast they respond, and how tolerant they may be, all change from one community to another. In some places, police policy is strict and justice is swift and in others, easy-going and forgetful. In some jurisdictions they have high powered militia and in others is hand to hand combat. This relates to the important role our genetic predispositions play and how they may make the difference in symptom manifestation. Genetics is an important factor in IBD. The incidence of IBD in different countries in the world is extremely variable, from very high in North-Eastern Europe, to very rare in Asia. Siblings of patients are also at greater risk of developing IBD. There are specific chromosomal markers associated with increase risk to get Crohn’s. More interestingly, are special animal models where scientists used genetic engineering to eliminate one of the signals that are used for the ID process or to regulate the “police” movement in and out of the gut. These animals have developed disease similar to IBD. In other experiments, blocking a certain signal stopped the inflammation for several months, and this procedure is already available in human trials. The genetic code has a lot to do with the way the body police respond and interact, but genetics by itself cannot explain it all.
Genetic codings take many generations to change, even a little bit. So how can we explain observations regarding the changes in IBD occurrence rate in migrants? We know that migrants from countries with low IBD rates will get more IBD when they move to countries like Canada or the UK where the IBD rate is higher. Looking at the Jewish people, we see this interesting phenomenon very well. The genetic inheritance of the Jews has more in common within the nation than with their neighbours. However, studies show that the rat of IBD varies to reflect their current locale, high rate in Russia, low rate in Asia. These population studies teach us the importance of environment on IBD as well as genetic influences. There are differences in food, food additives, bacteria, life style, and health care systems that somehow contribute to the expression of IBD.
Things are more complex when we move our focus from populations to individuals. We know that IBD behaves differently in different people. Some patients form stricture, some fistulae. Some develop limited inflammation while others experience wide spread disease. Some people have joint problems and some liver or skin disease. Some require lots of medications, some are almost without symptoms. There are enormous variations from one person to another, almost as if these were different conditions. This is why treatment of IBD is such a challenge. There is no one cure for all. The apparently logical solution often does not stand u p to the trial of life, because life is much too complex and our knowledge too limited. There are too many variables. What started the process may be different from person to person, and what makes it go on and on may be different still.
How can we tell what is a good treatment? It is not simple to study treatment of IBD, as patients require an individualized plan. One of the most important studies in IBD was done twenty years ago in the USA. People with Crohn’s were treated with either steroids, sulfasalazine, 6-MP, or a placebo. The steroids worked better than the placebo. Surprisingly however, 30% of the patients receiving the placebo went into remission. In a second phase of that study, placebo was as good as any of the other agents for the maintenance of remission. This indicates that there is a significant number, as many as one third of patients that will stay better for up to two years. This is why anecdotal reports, or poorly designed studies, are of no use in IBD. They detract and confuse. Special diets that reportedly heal IBD are only addressing the symptoms, not the inflammation. While the patient becomes somewhat more comfortable, the disease process is still active. Antibiotics may help, but not everybody responds to these either.
As I mentioned earlier, the majority of patient with IBD will try an alternative medicine. In keeping with the analogy represented here, the natural medicines offer a different approach in encouraging the “reinforcements” to go home. Most adults may not have much to lose in trying different therapies but it is a very different situation for children. The time the body needs to grow and the mind to develop is a crucial and sensitive period. Optimal treatment, adequate attention to nutrition and addressing nutrient deficiencies are extremely important. This is not to say that we should not look for alternatives and new approaches. We need to keep our minds open. However, our seeking should be controlled and careful, so we can sort out the benefits of any new alternatives without losing anything that we have already gained.