Study Links Leaky Gut to Crohn’s Disease

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Crohn’s and Colitis Canada is pleased to announce that the world-renowned Genetic, Environmental, Microbial (GEM) Project has led to a significant finding. Launched in 2008, the GEM Project is the world’s largest clinical study investigating the causes of Crohn’s disease. In this study of prospective development of Crohn’s, researchers have been monitoring thousands of healthy individuals who have a sibling or parent with the disease and are tracking their diet, immune function, intestinal barriers, microbiome, genetics, and environment. So far, 95 participants have been diagnosed with Crohn’s disease, a debilitating, chronic condition for which there is currently no cure. Fifty of the 95 participated in a recent gut barrier analysis. 

“The project’s design was based on a simple question: why does one person develop Crohn’s disease instead of someone else?” says Dr. Croitoru, the lead investigator. “With over 10 years of data and technology that has evolved, we are able to perform analyses that we never dreamed of in 2008. No one else in the world has such a cohort of people, samples, and data to investigate the causes of Crohn’s disease. We have long focused on how to control the symptoms and the inflammation. Here, we are asking how to cure the disease, and we now have intriguing data about the potential early triggers of Crohn’s,” adds Dr. Croitoru. The gut barrier analysis, Increased Intestinal Permeability is Associated with Later Development of Crohn’s Disease published in the AGA (American Gastroenterological Association) journal “Gastroenterology” sheds further light on these predictors.

The study assessed whether defects in the gut barrier function could be linked to a person’s future risk of developing Crohn’s disease. The lining of a person’s gut serves as a barrier separating gut microbes and the immune response. It has long been thought that a breakdown of this barrier (called “leaky gut”) could lead to the development of gut inflammation. Although healthy relatives of Crohn’s disease patients may have altered barrier function, this has never been shown to precede or lead to development of Crohn’s disease. 

The study found that healthy first-degree relatives of Crohn’s disease patients, who eventually developed Crohn’s disease themselves, had abnormal LacMan ratios when enrolled in the study. Gut barrier integrity was measured using Lactulose Mannitol Ratio or LacMan ratio. Lactulose is a large sugar that normally does not cross the gut barrier. Higher levels of lactulose in the urine is suggestive of a leaky gut. This is the first report of pre-existing abnormal barrier function in a large study of healthy individuals followed over time for the development of Crohn’s disease demonstrating that the LacMan ratio can predict disease. 

During this phase of the GEM Project, researchers are seeking to develop predictive tests that can identify individuals who will develop the disease, even before symptoms appear.    Crohn’s and Colitis Canada is thankful toward their donors and to The Leona M. and Harry B. Helmsley Charitable Trust for believing in research like the GEM Project, and to the participants and researchers who make these advancements possible.   “Crohn’s and Colitis Canada is proud to be driving world-renowned, game-changing Crohn’s and colitis research thanks to the passion and curiosity of Canadian researchers like Dr. Ken Croitoru and his team, combined with the generous support and patience of our donors,” says Mina Mawani, President and CEO of Crohn’s and Colitis Canada. “High-impact research like the GEM Project takes significant time and money, but the value of the research outcomes makes the investment worthwhile, as we find ways to prevent these devastating diseases,” she adds.

While the GEM Project focuses on Crohn’s disease, the research also feeds into the understanding of ulcerative colitis, a similar inflammatory bowel disease (IBD), which could lead to more targeted, and more effective, treatments.

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