In this issue, I’m highlighting some cutting-edge research that my colleagues at Cleveland Clinic are conducting on inflammatory bowel disease. Their work could help to advance our understanding of IBD from a mechanistic standpoint and also produce some really exciting treatments that could significantly improve the lives of patients with IBD.

One promising area of research is breath testing for volatile organic compounds (VOCs) produced in the gastrointestinal tract in patients with an ileal pouch-anal anastomosis (IPAA). Half of our patients with an IPAA develop pouchitis. Currently, diagnosing it requires endoscopic investigation along with biopsies. Breath testing would be a nice noninvasive alternative. Moreover, if breath testing is found to accurately measure inflammation in the pouch, it could potentially be studied for measuring inflammation in the GI tract and ultimately aid in the diagnosis and management of patients with Crohn’s disease and ulcerative colitis.

Another exciting area of research here at Cleveland Clinic is the use of mesenchymal stem cells (MSCs) for treating a number of conditions in IBD, ranging from fistulas in both adults and children to, more recently, luminal disease in ulcerative colitis and Crohn’s colitis. The healing rate for fistulas with the standard of care—setons and anti-tumor necrosis factor agents—is only about 30%, and if more aggressive surgery is needed, patients are often left with an ostomy bag. Work performed at Cleveland Clinic and elsewhere has shown that injection of MSCs—to be distinguished from embryonic stem cells—into fistula tracts can heal up to 80% of fistulas, avoiding the need for systemic therapy and surgery. Now, by looking at use of MSCs to treat ulcerative colitis or Crohn’s colitis, my colleagues’ research stands to revolutionize IBD care once again.

Capturing IBD ‘Breathprints’

Taha Qazi, MD, a gastroenterologist at Cleveland Clinic, has been leading the search for IBD “breathprints,” the combination of VOCs unique to patients with IBD. VOCs are produced through metabolism or inflammation, or are by-products of microbial activity. In any given breath, one exhales at least 3,000 different compounds.

Dr. Qazi’s team is using selective ion flow tube mass spectrometry to identify the IBD breathprints, with their current work focusing on patients with pouchitis.

“Our group has shown that patients with pouches have a distinct breath profile of VOCs, compared to patients with their gastrointestinal system intact,” Dr. Qazi said.

In a study underway, Dr. Qazi and his team are aiming to enroll 65 patients presenting for a pouch evaluation and to obtain a breath sample before endoscopic evaluation. If they can accurately correlate endoscopic pouchitis findings with breathprints, clinicians may eventually have a noninvasive tool for measuring pouch inflammation in their clinical armamentarium. Furthermore, if they can develop an at-home device based on this technology, patients likely would welcome the convenience of monitoring their disease remotely, and the modality could be used to personalize medical management, Dr. Qazi said.

“Metabolomics holds significant promise in allowing us to better characterize, classify and assess disease states,” he said.

Stem Cells for Colitis

Previous studies have found that multiple intravenous infusions of MSCs can improve luminal disease activity in patients with Crohn’s disease or ulcerative colitis, without causing serious adverse events (e.g., Gut Liver 2018;12[1]:73-78. doi:10.5009/gnl17035). Amy Lightner, MD, the director of the Center for Regenerative Medicine and Surgery at Cleveland Clinic, is examining the efficacy of targeted injections of MSCs directly into the submucosal layer of the colon wall.

“Our lab’s prior work suggests that local delivery might be a more effective approach to administering these cells, allowing us to put them right where they are needed and in higher concentrations,” she said.

Dr. Lightner said local delivery is more successful in treating perianal fistulas, likely because some cells administered intravenously get trapped inside the lungs. “Similar to what we do in fistulizing Crohn’s disease, we are using a small needle to directly inject cells at the time of colonoscopy to treat intestinal inflammation,” she said.

Dr. Lightner said she hopes her group’s research will answer a number of questions: What is the best way to deliver cells? What is the optimal dose and time to retreatment? And which patients respond best to stem cell therapy? Once these questions are addressed, IBD clinicians and patients may find their IBD treatment options expanded.

“It’s an exciting time for regenerative medicine for IBD,” Dr. Lightner said. “If patients heal from this approach, it would offer an alternative therapy to biologics, with potentially fewer side effects.”

—Compiled and written by David Wild