Changes in Gut Microbiome Precede Crohn’s Disease Onset by up to Five Years

By Andreu Prados, PhD, BPharm, RDN, and Natasha Haskey PhD, RD

While the origin of Crohn’s disease (CD) is not completely understood, emerging studies have involved the gut microbiome in the onset and progression of gut inflammation. Alterations in the gut microbiome have been described in CD, but it is unknown whether they are the origin of CD or the consequence of gut inflammation or drug treatment. 

Recent findings¹ from the Crohn’s and Colitis Canada Genetic Environmental Microbial (GEM) project team show for the first time that changes in the gut microbiome composition precede CD onset by up to five years, supporting a causal role of gut microbiome alterations in CD.

The researchers developed a risk score using a machine-learning model that included microbiome-related data (abundance of bacterial taxa and diversity), age and sex from almost 3500 healthy first-degree relatives of patients with CD around the world. At the beginning of the study participants had a median age of 17 years and then were followed for 5.5 years.

The top five taxa that contributed the most to predicting CD onset were the genera Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group of Oscillospiraceae, and Roseburia. The abundance of Ruminococcus torques and Blautia was an important contributor to CD onset, which are mucin degraders often increased in those with IBD. In contrast, Roseburia and Faecalibacterium genus had a protective effect on the development of inflammation. 

The changes in microbial functions was linked to a decrease in substances that help fight inflammation or act as antioxidants. Moreover, the microbiome risk score was linked to CD independent of the presence or absence of gut inflammation indicated by fecal calprotectin levels. 

Altogether, these findings show that the gut microbiome of those who develop Crohn’s disease is different from those who remain healthy years before they develop the disease. This discovery paves the way for microbiome-targeted interventions to prevent and treat CD.

As Nathan Grellier and colleagues highlight in an accompanying commentary, “We have never been so close to solving the chicken-and-egg enigma on gut dysbiosis in Crohn’s disease”.

^{1. Raygoza Garay JA, Turpin W, Lee SH, et al. Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives. Gastroenterology. 2023;165(3):670-681. doi:10.1053/j.gastro.2023.05.032}

^‍‍About the writers:

‍Dr. Andreu Prados is a science and medical writer specializing in making reliable evidence of non-prescription therapeutics for gastrointestinal conditions understandable, engaging and ready for use for healthcare professionals and patients. He holds bachelor’s degrees in Pharmacy and Human Nutrition and Dietetics and a PhD in nutrition communication.

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Dr. Natasha Haskey is a clinical scientist and Registered Dietitian with over 20 years of practical experience in nutrition therapy for IBD.  In 2022, she completed her doctorate at the Center for Microbiome and Inflammation Research at the University of British Columbia in Okanagan, Canada, examining how a Mediterranean diet influenced clinical disease activity, inflammation and the microbiome in ulcerative colitis. She co-authored the textbook called "Gut Microbiota: Interactive effects on nutrition and health"

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