The disease, which is characterized as chronic inflammation in the gastrointestinal tract, causes such symptoms as severe diarrhea, stomach pain and bowel urgency. Those with IBD, which encompasses conditions like ulcerative colitis and Crohn’s disease, may also experience fevers, vomiting, weight loss and extreme tiredness that can interfere with daily functioning. Some complications of the disease—such as perforation of the intestines—can even be life-threatening.
While there are ways to manage IBD, there is no cure for the devastating and destructive disease, and identifying new treatments is challenging since relatively little is known about how it originates.
But at Janssen Research & Development, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, researchers are aiming to change that. Esi Lamousé-Smith, M.D., Ph.D., Senior Director, Translational Science & Medicine, Immunology, and a team of colleagues are working to help unravel the mysteries of IBD by pursuing new avenues of treatment that can help address disturbances in the gut microbiome, which have been implicated in the development of the condition.
For Crohn’s and Colitis Awareness Week, we sat down with Dr. Lamousé-Smith to learn more about the microbiome’s role in IBD—and what the future of treating the disease could look like.
Q:
What is life like for people who have IBD?
A:
IBD can take a significant toll on almost every aspect of a patient’s life. Before I came to Janssen in 2017, I treated children and teenagers who had it, and I saw how much they struggled.
They would be going to the bathroom all the time, experiencing severe abdominal pain and losing weight. And they were dealing with this at the most important time in their lives, when they were developing and getting an education. School was very hard for them due to lack of energy and concentration, and also because they were so tied to the bathroom.
Thankfully, there are very good medications for managing IBD, and it was always amazing to see the transformation children underwent when they started treatment.
Q:
So how is IBD currently treated?
A:
One way is with biologic medications, which are created from living cells, and target specific proteins involved with IBD. Other medications include antibiotics; immunomodulators, which help regulate the immune system; aminosalicylates and short courses of corticosteroids (both of which work to lower inflammation).
All of these drugs can get inflammation under control and decrease immune response, so the patient can achieve remission and maintain it. However, while these treatments can potentially keep patients in remission for years, they’re not 100% effective. People can continue to experience flare-ups of the disease for the rest of their lives.
And sometimes, surgery may be necessary to remove portions of the intestine that have been damaged by inflammation. Surgery can relieve some symptoms of IBD, but it isn’t a cure; patients still have to be monitored for recurrence, and some could require additional surgery. So there is an urgent need to develop better, less invasive treatments for the disease.
We are also investigating ways to restore the intestinal epithelial barrier in patients with IBD, which is a new frontier in treating this disease.
Q:
What role does the gut microbiome play in the development of IBD?
A:
The gut microbiome refers to the bacteria, viruses and fungi—both good and bad—that live in the gut. These microbes and the substances they produce are key to establishing the interplay and balance of immunity in the body.
How they perform these functions is still an area of investigation—we’re really just at the tip of the iceberg in understanding it—but we have gained quite a bit of insight using experimental models.
In a healthy person, the balance of these good and bad microbes remains relatively stable. But that’s not the case for people with IBD.
We now have a library of data demonstrating that these patients have a microbiome that is abnormal. Dysbiosis, or an imbalance of good and bad bacteria, develops—perhaps triggered by genetics or such environmental factors as diet and antibiotic use. When dysbiosis occurs and the body is unable to reset itself on its own and return to homeostasis, it can lead to a cascade of events that may cause IBD and other inflammatory conditions.
Q:
What type of treatment could potentially help restore the balance of gut microbes in patients with IBD?
A:
There are actually several opportunities for accomplishing this that we’re researching. In fact, successfully treating IBD may require a combination of approaches; there’s not going to be one miracle cure.
One method may be to deliver a live bacterial product—a mix of bacteria that is usually found in healthy people—to the gut microbiome of patients with IBD. This could be done via fecal transplant or, perhaps, an oral fecal capsule.
However, we cannot look at the microbiome in isolation in our pursuit of new therapies. At Janssen, we are also investigating ways to restore the intestinal epithelial barrier in patients with IBD, which is a new frontier in treating this disease.
The intestinal epithelial barrier is a layer of cells that lines the intestines and plays a critical role in regulating a healthy gut microbiome. We know that the origin and progression of IBD is linked to damage to the barrier, so if we can restore both homeostasis and epithelial barrier defense, we will restore a healthy microbiome.
We have conducted a great deal of work with live microbials—that is, the microorganisms that live in the gut microbiome and support digestion and immunity—and we’re now using the knowledge we’ve gained to pursue small molecules that can help enhance the function of the intestinal barrier.
Q:
What inspired you to pursue treatments for IBD at Janssen?
A:
I had been working in academia and was inspired to join Janssen because I felt that I would be able to reach a much greater number of patients at a company with such deep experience in the IBD space.
I wanted to be connected to the science and to clinical advancements—and I’ve been profoundly impressed by the talent.
The work our scientists do is scientifically and clinically rigorous, which brings a whole new level of intellectual satisfaction to my work and increases my determination to develop therapies that could help change the lives of people who have IBD.
