Increased Intestinal Permeability Is Associated With Later Development of Crohn's Disease.

Area of Science:

• Gastroenterology
• Immunology
• Genetics

Background:

• Crohn's disease (CD) is linked to increased intestinal permeability, but its causal role remains unclear.
• Investigating intestinal permeability as a predictor of CD onset is crucial for understanding disease pathogenesis.
• First-degree relatives of CD patients represent a high-risk cohort for prospective studies.

Purpose of the Study:

• To prospectively determine if increased intestinal permeability predicts the future development of Crohn's disease.
• To assess the association between baseline intestinal permeability and subsequent CD diagnosis in asymptomatic individuals.
• To evaluate the utility of intestinal permeability as a biomarker for CD risk.

Main Methods:

• A prospective study of 1420 asymptomatic first-degree relatives of CD patients aged 6-35 years.
• Intestinal permeability assessed using the lactulose-to-mannitol ratio (LMR) at recruitment.
• Follow-up for CD diagnosis over a median of 7.8 years using Cox proportional hazards models.

Main Results:

• An abnormal LMR (>0.03) at baseline was significantly associated with a future CD diagnosis (HR, 3.03; P < .001).
• This association remained significant even when LMR was measured over 3 years prior to CD diagnosis (HR, 1.62; P = .029).
• 50 participants developed CD, while 1370 remained asymptomatic during the follow-up period.

Conclusions:

• Increased intestinal permeability is a significant predictor of later Crohn's disease development.
• These findings support a pathogenic model where impaired intestinal barrier function contributes to CD onset.
• Abnormal gut barrier function may serve as a valuable biomarker for identifying individuals at high risk of CD.