Dr. Kenneth Croitoru
Gastroenterologist at Mount Sinai Hospital
Inflammatory bowel disease (IBD) affects so many people from young to all stages in life, 1/250 people have IBD.
When someone asks what causes it, we say “we think you have a genetic predisposition and that somehow alters the way your immune system responds to the environment including the microbes that are in your gut”. Having said that we do not really understand what that means, we cannot tell you what triggers the disease or what changes in the gut microbiome cause the disease, we know some genes are associated with increased risk but we are not even sure how those genes or defects in those genes lead to the disease. There are a lot of unknowns.
We have new technologies that allow us to map the microbiome. Somewhere in there may be an answer to what changes occur before disease that are associated with the risk of developing disease. This technology allows us to use genetic sequencing to define the composition – to tell you what is there in the microbiome.
The Crohn’s Colitis Canada GEM project is a study that looks at people who are at risk of developing Crohn’s disease. We identify them because they are a first-degree relative of someone who has Crohn’s, they have an increased risk of developing the disease over their life. We have collected 5000 of these individuals and we’ve been watching them for over ten years. About 100 have developed the disease. We have been sampling these people while they were healthy and have been waiting and watching to see who has developed the disease. Now we are able to see what was there when they were healthy that made them different from the rest of the group who stayed healthy. We now have a number of things that we have identified that are related to the risk of them developing Crohn’s disease. There is a genetic predisposition, that we knew already, we measured gut barrier function and found that leaky gut is present before the disease happens and is associated with the risk of disease. We’ve also looked at the microbiome composition and compared differences in those people who developed disease to the control group of individuals who did not, and we actually have a pattern that has emerged that is associated with the risk of disease. With this information we can look at those bacteria that are different that are associated with the risk of disease or may be associated with protecting you from developing the disease. Now we can try and ask the questions: what are those bacteria doing, how are they affecting the gut and how are they affecting the inflammation that occurs.
Doing research on humans is difficult for many reasons, one of those reasons being that you cannot manipulate the system, you cannot do something to a person to try and see how things will change. To really understand mechanisms, you need to go to an animal model. We’re beginning to explore using animal models with these specific bacteria to try and understand how they may be inducing inflammation. We are beginning to show evidence of changes in the microbiome that may be related to your risk of disease, and we think that this holds the answers to what triggers disease maybe even what causes the disease and with that we hope we can develop better targets for something that can be changed.
The environment is another important contributor to what may be triggering disease the difficulty there is how to go looking for what in the environment is responsible. You could look at environmental toxins, pollutions, something in the water, and of course something in the foods you eat, yet it is a very difficult task. That said there are doctors that are trying to conduct this research and with new technologies out there that allow us to look at toxins by measuring toxins in the hair, toxins in the blood etc. we may be able to better understand the role the environment has in triggering disease.
Lastly, diet is a very interesting area seeing as there are just as many hypotheses about which diets that are good for you as there are foods. The problem is that although many of these ideas come from some understanding of how these diets may affect the gut and inflammation, we actually don’t know what is responsible for contributing to the inflammation and we also don’t really know what changes in diet would help. As part of our study, we are beginning to look at the diets these individuals have had and look to see if there are differences that may explain some of the changes in the microbiome and even some of the risks associated with developing disease.