Increased intestinal permeability may be associated with the development of Crohn disease (CD), according to study results published in Gastroenterology.

Researchers examined intestinal permeability measured by the urinary fractional excretion of lactulose to mannitol ratio (LMR) at study recruitment in 1420 asymptomatic first-degree relatives (aged 6-35 years) of patients with CD (collected from 2008 through 2015). The participants were reviewed for a diagnosis of CD from 2008 to 2017, and analyzed using the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR.

Before entry to the study, participants were screened using a questionnaire to specifically exclude any history or symptoms of IBD or any other gastrointestinal diseases. The mean age of the participants was 19±7.8 years, and 42.2% were female.


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An abnormal LMR (defined as >0.03) was associated with diagnosis of CD during the follow-up period. A total of 50 individuals developed CD during the study period, along with 1370 individuals who remained asymptomatic to date (October 2017). Baseline LMR measurements of participants who later developed CD were significantly higher than those of individuals who remained asymptomatic (P <.015). Furthermore, when the LMR test was performed >3 years before the CD diagnosis, the association was still significant (hazard ratio, 1.62; P =.029).

These results suggest abnormal gut barrier function might serve as a biomarker for the risk of CD onset. The cause of CD is still unknown, and case control studies have determined that gut barrier function is abnormal in patients with CD compared to controls However, it is uncertain whether the abnormality of the gut barrier is a reflection of the luminal environment, a barrier defect, or the consequence of an injury. An analysis of the genome-wide association of LMR showed that host genetics give a small contribution to an abnormal LMR10, which implies that abnormal LMR may be more likely a reflection of an environmental trigger or injury.

Investigators noted, “The absence of a cure for CD emphasizes the importance of this study since the identification of early preclinical markers of disease could lead us toward prevention strategies.”

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Reference

Williams T, S-H Lee, Raygoza Garay JA, et al; on behalf of the CCC GEM Project Research Consortium. Increased intestinal permeability is associated with later development of Crohn’s disease. Gastroenterology. Published online August 10, 2020. doi:10.1053/j.gastro.2020.08.005