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

Gastroenterology. 2020 Dec;159(6):2092-2100.e5. doi: 10.1053/j.gastro.2020.08.005. Epub 2020 Aug 10.


Background & aims: Increased intestinal permeability has been associated with Crohn's disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD.

Methods: We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6-35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR.

Results: An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64-5.63; P = 3.97 × 10-4). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051-2.50; P = .029).

Conclusions: Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.

Keywords: Crohn’s Risk; FDR Study; Gut Barrier; IBD.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Crohn Disease / epidemiology*
  • Crohn Disease / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Intestinal Mucosa / pathology*
  • Lactulose / administration & dosage
  • Lactulose / metabolism
  • Lactulose / urine
  • Male
  • Mannitol / administration & dosage
  • Mannitol / metabolism
  • Mannitol / urine
  • Permeability
  • Prospective Studies
  • Renal Elimination
  • Risk Factors
  • Young Adult


  • Mannitol
  • Lactulose

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