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GEM Study //
Turpin W, Lee SH, Raygoza Garay JA, Madsen KL, Meddings JB, Bedrani L, Power N, Espin-Garcia O, Xu W, Smith MI, Griffiths AM, Moayyedi P, Turner D, Seidman EG, Steinhart HA, Marshall JK, Jacobson K, Mack D, Huynh H, Bernstein CN, Paterson AD, Croitoru K; CCC GEM Project Research Consortium. Increased Intestinal Permeability is Associated with Later Development of Crohn's Disease. Gastroenterology 2020; 159;2092-2100.
This study was from the Crohns and Colitis Canada sponsored GEM study. Increased intestinal permeability has been associated with Crohn's disease, 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 Crohn's disease. We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio at recruitment in 1420 asymptomatic first-degree relatives (6-35 years old) of patients with Crohn's disease (collected from 2008 through 2015). Participants were then followed up for a diagnosis of Crohn's disease from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed Crohn's disease 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 Crohn's disease based on the baseline lactulose-to-mannitol ratio. An abnormal lactulose-to-mannitol ratio (>0.03) was associated with a diagnosis of Crohn's disease 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 Crohn's disease (hazard ratio, 1.62; 95% CI, 1.051-2.50; P = .029).
We concluded that 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.