Increased Intestinal Permeability Is Associated With Later Development of Crohn's Disease.
Crohn’s Risk
FDR Study
Gut Barrier
IBD
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
02
04
2020
revised:
21
07
2020
accepted:
04
08
2020
pubmed:
14
8
2020
medline:
16
4
2021
entrez:
14
8
2020
Statut:
ppublish
Résumé
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. 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. 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 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.
Sections du résumé
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
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.
Identifiants
pubmed: 32791132
pii: S0016-5085(20)35021-6
doi: 10.1053/j.gastro.2020.08.005
pii:
doi:
Substances chimiques
Mannitol
3OWL53L36A
Lactulose
4618-18-2
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2092-2100.e5Subventions
Organisme : CIHR
ID : CMF108031
Pays : Canada
Investigateurs
Maria Abreu
(M)
Paul Beck
(P)
Charles Bernstein
(C)
Kenneth Croitoru
(K)
Leo Dieleman
(L)
Brian Feagan
(B)
Anne Griffiths
(A)
David Guttman
(D)
Kevan Jacobson
(K)
Gilaad Kaplan
(G)
Denis O Krause
(DO)
Karen Madsen
(K)
John Marshall
(J)
Paul Moayyedi
(P)
Mark Ropeleski
(M)
Ernest Seidman
(E)
Mark Silverberg
(M)
Scott Snapper
(S)
Andy Stadnyk
(A)
Hillary Steinhart
(H)
Michael Surette
(M)
Dan Turner
(D)
Thomas Walters
(T)
Bruce Vallance
(B)
Guy Aumais
(G)
Alain Bitton
(A)
Maria Cino
(M)
Jeff Critch
(J)
Lee Denson
(L)
Colette Deslandres
(C)
Wael El-Matary
(W)
Hans Herfarth
(H)
Peter Higgins
(P)
Hien Huynh
(H)
Jeff Hyams
(J)
David Mack
(D)
Jerry McGrath
(J)
Anthony Otley
(A)
Remo Panancionne
(R)
Guy Aumais
(G)
Robert Baldassano
(R)
Charles Bernstein
(C)
Maria Cino
(M)
Lee Denson
(L)
Colette Deslandres
(C)
Wael El-Matary
(W)
Anne M Griffiths
(AM)
Charlotte Hedin
(C)
Hans Herfarth
(H)
Peter Higgins
(P)
Seamus Hussey
(S)
Hien Hyams
(H)
Kevan Jacobson
(K)
David Keljo
(D)
David Kevans
(D)
Charlie Lees
(C)
David Mack
(D)
John Marshall
(J)
Jerry McGrath
(J)
Sanjay Murthy
(S)
Anthony Otley
(A)
Remo Panaccione
(R)
Nimisha Parekh
(N)
Sophie Plamondon
(S)
Graham Radford-Smith
(G)
Mark Ropeleski
(M)
Joel Rosh
(J)
David Rubin
(D)
Michael Schultz
(M)
Ernest Seidman
(E)
Corey Siegel
(C)
Scott Snapper
(S)
Hillary Steinhart
(H)
Dan Turner
(D)
Informations de copyright
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.