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

2020; Elsevier BV; Volume: 159; Issue: 6 Linguagem: Inglês

10.1053/j.gastro.2020.08.005

1528-0012

Williams Turpin, Sun-Ho Lee, Juan A. Raygoza Garay, Karen Madsen, Jonathan B. Meddings, Larbi Bedrani, Namita Power, Osvaldo Espin‐Garcia, Wei Xu, Michelle I. Smith, Anne M. Griffiths, Paul Moayyedi, Dan Turner, Ernest G. Seidman, A. Hillary Steinhart, John K. Marshall, Kevan Jacobson, David Mack, Hien Q. Huynh, Çharles N. Bernstein, Andrew D. Paterson, Kenneth Croitoru, Maria Abreu, Paul L. Beck, Çharles N. Bernstein, Kenneth Croitoru, Leo Dieleman, Brian Feagan, Anne M. Griffiths, David S. Guttman, Kevan Jacobson, Gilaad G. Kaplan, Denis O. Krause, Karen Madsen, John K. Marshall, Paul Moayyedi, Mark J. Ropeleski, Ernest G. Seidman, Mark S. Silverberg, Scott B. Snapper, Andy Stadnyk, Hillary Steinhart, Michael G. Surette, Dan Turner, Thomas D. Walters, Bruce A. Vallance, Guy Aumais, Alain Bitton, Maria Cino, Jeff Critch, Lee A. Denson, Colette Deslandres, Wael El‐Matary, Hans Herfarth, Peter Higgins, Hien Q. Huynh, Jeff Hyams, David Mack, Jerry McGrath, Anthony Otley, Remo Panancionne, Guy Aumais, Robert N. Baldassano, Çharles N. Bernstein, Maria Cino, Lee A. Denson, Colette Deslandres, Wael El‐Matary, Anne M. Griffiths, Charlotte Hedin, Hans Herfarth, Peter Higgins, Séamus Hussey, Hien Hyams, Kevan Jacobson, David J. Keljo, David Kevans, Charlie W. Lees, David Mack, John K. Marshall, Jerry McGrath, Sanjay K. Murthy, Anthony Otley, Remo Panaccione, Nimisha Parekh, Sophie Plamondon, Graham Radford-Smith, Mark J. Ropeleski, Joel R. Rosh, David T. Rubin, Michael Schultz, Ernest G. Seidman, Corey A. Siegel, Scott B. Snapper, Hillary Steinhart, Dan Turner,

Drug Transport and Resistance Mechanisms

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.