Does Gut Microbiome Contribute to — or Result From — Crohn’s Disease?

Researchers have identified specific microbiota that appear to predict the development of Crohn’s disease (CD) among healthy first-degree relatives of patients with CD, they reported recently in Gastroenterology.

“This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD,” the authors wrote.

The present hypothesis concerning the etiology of CD is among people with genetic susceptibility, microbial or environmental factors —or perhaps a combination—cause intestinal inflammation that becomes chronic. The investigators noted previous case-control studies of patients with CD “have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment.”

This prospective cohort study recruited 3483 healthy first-degree relatives of patients with CD to identify the gut microbiome composition that precedes the onset of CD and whether, and to what extent, the microbiome may predict the risk of developing CD. The investigators used a machine learning approach to analyze the gut microbiome in an effort to define a microbial signature associated with the development of CD.

They assessed the performance of the model in an independent validation cohort and found that “the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65).”

The authors noted that “The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia.”

Reference:

Garay JAR, 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: https://doi.org/10.1053/j.gastro.2023.05.032