Montreal researchers uncover possible treatment for inflammatory bowel disease

Researchers from Montreal Clinical Research Institute (IRCM) have identified a new molecule, naturally produced in the body, could be used to treat inflammatory bowel disease (IBD).

In a study published in the journal Blood earlier this month, researchers showed that Beta-hydroxybutyrate (BHB), a substance humans produce while fasting or on a ketogenic diet can reduce inflammation in intestinal tissue in mice.

Emilia Liana Falcone, director of the microbiome and defence research unit at IRCM, who led the nearly decade-long study, says she originally started out study a very specific and rare inherited disease called chronic granulomatous disease (CGD) that makes individuals susceptible to infections and leads to inflammatory bowel diseases in half of cases.

“I thought this was a very interesting population to study to understand much more about what causes and drives inflammatory bowel disease to see if we could apply what we learn to individuals in the general population who would have what we call conventional inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis,” said Falcone.

“We started off by examining our mice with chronic granulomatous disease and they had intestinal inflammation and we treated them first with a ketogenic diet to see if this could reduce the severity of the intestinal inflammation, which it did,” Falcone explained.

IBD is a chronic disease affecting the digestive system whose symptoms can range from abdominal pain and cramps, fever, fatigue to weight loss and arthritis. Its cause is still unknown.

In Canada, over 322,000 people suffered from a form of IBD according to a 2023 study published by Crohn’s & Colitis Canada, a charity that funds research on IBD. With about 11,000 Canadians diagnosed with Crohn’s diseases and colitis, the numbers expected to reach nearly half a million by 2035.

After finding the benefits of BHB, Falcone says the team set off to isolate the molecule and use it in more trials throughout the study, to determine whether it could be used without having to follow a ketogenic diet.

While BHB is being considered to treat chronic granulomatous (CGD), Falcone says her results indicate it might also be used to treat other more common forms of IBD, as it can block inflammatory responses.

“As a final step, we did the evaluation using blood cells from humans to see if technically the molecule can still block the inflammasome in these cells — and yes, it did,” she said.

With the preclinical phase over, Falcone says she has been in discussions with the National Institutes of Health in the U.S. where she trained in renowned researcher and National Academy of Medicine recipient, Steve Holland’s laboratory.

“They follow one of the world’s largest cohorts of patients with this disease, so we have been discussing if this could be something of interest potentially to do in the future,” Falcone says, “That’s exciting!”