Crohn’s disease is a complicated chronic disorder, the complexity of which has only become clear during the last decade. It has become increasingly evident that your food pattern and gut microbiota seem to play an important role in the development of the condition. Severine Vermeire, a renowned gastroenterologist at KU Leuven, discusses the latest research and treatment options, from antibiotics to stool transplantation, and explains why the most beautiful day in her life might not be that far in the future.
At the age of 18, Severine Vermeire was determined to study medicine. She graduated in ’95 at the KU Leuven. She specialized in gastroenterology and combined this with a PhD. She performed research at the University of Oxford and at McGill University (Montreal). Now, she works as a gastroenterologist at the UZ Leuven and leads a research team of 30 people, including PhD students, postdoctoral fellows, industry researchers and lab assistants. Vermeire: “It’s like we run a small company next to our work in the clinical practice. On paper I work 50% as a researcher and 50% as a doctor, but you cannot squeeze patient care into a fixed amount of hours. At the same time, I need to make sure that enough money comes in to pay our research team, but I really love the synergy that results from the interaction between the clinic and the lab.”
Regional enteritis was first described in 1932 by Dr. Burrill B. Crohn, who lent his name to the condition. It is a type of inflammatory bowel disease (IBD), where the body’s immune system turns against its own intestinal microbiota. The disease typically occurs in Western civilizations, and its incidence rose dramatically after WWII, reaching a plateau in the ‘90s. Vermeire: “Today, we don’t see anymore that the amount of new cases is still increasing on an annual basis, but the age of onset is decreasing. People nowadays get affected at a younger age than a decade ago. The same phenomena also started to appear in the Asian countries around the new millennium”.
People nowadays get affected at a younger age than a decade ago.
It’s in our food
Vermeire: “The exact cause of Crohn’s disease is still unknown, but there are some predisposing factors. Two to three decades ago, it became clear that there is a familial predisposition for Crohn’s, which could be either environmental or genetic. Since the ‘90s, effort is being put into determining the effect of our genes. During the last 5 to 7 years, as a reaction to the increasing awareness of the importance of the humane microbiome, scientists started to understand the influence of the gut flora on Crohn’s disease. They noticed that our diet has an extremely big influence on the intestinal microbiota, and hence on the progression of the disease.
The entire food production process has an enormous impact on how your food ends up on your plate. The food chain and our diet changed so drastically in the last century that this might be the root cause for Crohn’s.”
Our diet has an extremely big influence on the intestinal microbiota and hence on the disease.
Rather change your diet or have a faeces transplant?
Vermeire: “In our lab, we study how the gut flora is affected by the diet and which role these microbes have in IBD. We hope that within a couple of years, we will be able to tell patients which diet will be most beneficial for them. This is also what patients want. They want to treat their disease naturally rather than by using medicines. We will now start two clinical trials. In the first, we will put patients suffering from colitis, another type of IBD, on a particularly strict diet. They should eat no meat and no added sugars, but lots of fibres, vegetables and fruits. This means no cookies, no chocolate and no alcohol. It is an extremely healthy diet that I actually would like to advise to anyone. People generally eat way too much meat and should cut down their consumption of it.
We will transplant faeces from healthy people into the bowels of IBD patients.
In another trial, which we will conduct with the other university hospitals in Belgium, we will transplant faeces from healthy people into the bowels of IBD patients. A pilot study in Leuven and two bigger studies in Amsterdam and Canada showed no positive effect in patients with Crohn’s; however, one third of the patients suffering from colitis went into remission after transplantation. We are now trying to find out why it is working for certain patients. It seems to be extremely important who the donor is. In the healthy population, some people are 'super donors', having a very rich gut microbiota.
We are also investigating how we can manipulate the intestinal flora with antibiotics and how we can personalize this.”
Developing therapeutics hand-in-hand with the industry
Vermeire: “We cooperate with many pharmaceutical companies who are developing new drugs against Crohn’s. I like to be involved from a very early stage, so we can give input from the beginning and share expertise. We can help to find the patients that might react best to a compound, or decide how a treatment should be evaluated by looking for the right markers, preferably in blood or saliva. This is what thrives me, standing at the forefront of cutting-edge research.
For example, right before Christmas, we were proud to learn about the positive test results with Galapagos’ drug Filgotinib, in which our center was the lead investigator. That was a fantastic moment for the patients and for the company. Other companies we have been cooperating with include Genentech Roche, Pfizer, Takeda Pharmaceuticals, AbbVie, Merck, MSD and Celltrion.”
We’re close to healing
Vermeire: “Currently we are able to keep the disease under control in almost all patients. In most cases, we can guarantee a good quality of life. Young people can finish their education, and older people can stay at work. Biotechnological therapies have led to a big advancement in the last 15 years, so there are different options to treat patients. This year the new drug vedolizumab (Entyvio) became available, and next year ustekinumab (Stelara) most likely will as well, but this is not yet enough. Some patients have tried all available compounds but are still suffering. We have to keep looking for better treatment options until we can finally find a cure and, even more importantly, a way to prevent the disease.
Right now, we already have much knowledge about inheritance, the microbiome, the genome, metabolomics and the immune system. The big challenge is to combine all this information. Often, several aspects cause a disease. We need a holistic approach to analyze this massive amount of data and sort out the ideal solution. European projects are now being set up to work this out.
You have Crohn's disease, but I can cure you.
Based on the gigantic progress that has been made between 2010 and 2015, I think that we will be able to heal Crohn’s disease by 2030. It will be the most beautiful day of my life when I will be able to tell my patients: ‘You have Crohn’s disease, but I can cure you.’ “