Changing the Future of IBD Care with Gut-on-a-Chip

IBD is a chronic illness that causes inflammation of the gastrointestinal tract. In children, the two main types are Crohn’s disease (which can affect any part of the GI tract) and ulcerative colitis (which affects the large intestine). And rates of the disease are growing.

“There is definitely an increase in the incidence of IBD in the western world, so we’re seeing higher and higher rates,” said Dr. Salazar. “At Connecticut Children’s, we diagnose about 100 kids every year.” 

From every angle, IBD is a major disruption in a child’s life. Abdominal pain and persistent diarrhea are often daily struggles. The disease can cause slower height and weight gain, lead to malnutrition and nutrient deficiencies, and take a toll on mental health. Every flare—when symptoms and inflammation suddenly return—can mean missed school, canceled activities and more time in the hospital. For some children, surgery becomes unavoidable.

IBD patients usually require lifelong therapy to control the illness, but finding the right one is “an imprecise science,” said Dr. Salazar. “We don’t know which medication will work best for which patient. You watch and wait, and hope that’s the medication for them. If it’s not, you try a second medicine and go through the same process.” For families, that trial-and-error process can be lengthy and heartbreaking. “Four, five, six medications later, you don’t always get there. Some patients will not respond to any medicine and need surgery,” added Dr. Salazar.

To complicate matters further, just because IBD is a lifelong disease doesn’t mean that any given medication will work for a lifetime. 

“You can have a flare after losing response to the medication at any point,” Dr. Salazar said. “We have no way of predicting who loses response, or why.”

Dr. Salazar’s ultimate goal is to create personalized medicine that eliminates today’s trial-and-error treatment by immediately matching the right medication to a patient’s particular type of inflammation. But first, we need to understand more about the inflammation that IBD causes. That’s where gut-on-a-chip comes in.

Imagine recreating a tiny, functioning replica of a patient’s intestine—outside of their body. That’s what gut-on-a-chip technology allows researchers like Dr. Salazar to do. It starts with tissue collected during a colonoscopy. Those cells are then grown into what are called organoids, and then transferred to a small chip the size of a USB stick that mimics the natural environment of the intestine, complete with the mucus layer that normally protects the intestine from microbes.

“There is more and more evidence to show that IBD is caused by an abnormal interaction between the microbes in the gut and the intestinal epithelium [a layer of cells responsible for absorbing nutrients and blocking pathogens],” Dr. Salazar said. “Unfortunately, when we historically tried to recreate models for IBD, it was from tissue samples that had a lot of active disease. So, we weren’t able to zero in on the ‘big bang’ moment when disease actually begins. By the time we meet patients, by the time they show enough symptoms to see a doctor, all that inflammation is already happening.”

Gut-on-a-chip technology allows Dr. Salazar to take a new approach: recreating both healthy and diseased tissue from the same patient and observing what happens at the exact moment a healthy gut environment becomes inflamed. When do inflammatory cytokines (chemicals) show up? When does the protective mucus layer begin to disappear? When does the intestinal epithelium become permeable, allowing the free flow of microbes and triggering the immune system? Which bacteria are protective, and which are harmful to that individual patient?

Ulcerative colitis is a form of IBD that’s especially well-suited to this new research approach, since it can appear in two ways—either as pancolitis that results in inflammation throughout the entire colon or as partial colitis that is limited to the lower end of the large intestine. It is these partial colitis cases that Dr. Salazar has zeroed in on.

“Both the healthy and unhealthy sections of the colon are exposed to the same microbiome,” he explained, “so why is one part inflamed and the other normal? Dr. Hyams will say that it’s like someone took a magic marker and just drew a line, and, beyond that, you see healthy tissue.”

Dr. Salazar hypothesizes that the answer to that question may be that the normal tissue is not, in fact, “normal.” It simply may be in a pre-disease state that will eventually progress to full-blown inflammation. Collecting both types of tissue from patients with partial colitis will allow him and colleagues to experiment on and compare pre-disease and diseased tissues to “find what that final trigger is that sets the ball rolling.”  

His research team has already collected more than 20 patient samples from children with IBD, as well as other gastrointestinal diseases, and successfully grown functioning organoids and the populated gut chips, each of which takes a minimum of four to six weeks to create in the lab. The next step is finding the funding that will be needed to grow gut chips from more patients, conduct experiments with those chips, and build a biorepository of tissue, blood and stool samples.

While this research won’t change treatment for IBD tomorrow, the long-term potential is enormous. Dr. Salazar’s study is a critical step toward a deeper understanding of the inflammatory response in the human gut. The possibilities don’t stop with ulcerative colitis.  “Once we have the pathway set from patient, tissue, chip and experimental design, we can apply that to a lot of different GI diseases. So, things like necrotizing enterocolitis in newborns, eosinophilic esophagitis, and celiac disease,” Dr. Salazar said.

For families who have lived with the uncertainty of trial-and-error treatments, this research represents a turning point. The gut-on-a-chip model has the potential to shift the answer from we don’t know to we do know­, and toward a future where a child diagnosed with IBD can immediately get the medication that’s right for them—keeping them in school, on the playing field, and in the business of being a kid.

“The dream of gut-on-a-chip is to bring personalized medicine here,” Dr. Salazar said. “To be able to say, ‘you have this disease, we can create the chip, and we can know how your disease is going to behave in your body.’”

Without research there is no path forward to improve the lives of children with IBD. 

Dr. Jonathan Salazar was one of four finalists for a Connecticut Children’s Connection research grant in 2025. Watch highlights of last year’s funding selection event.