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

Williams Turpin; Sun-Ho Lee; Juan Antonio Raygoza Garay; Karen L 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 Huynh; Charles N Bernstein; Andrew D Paterson; Kenneth Croitoru

doi:10.1053/j.gastro.2020.08.005

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

Journal article

Open access

Peer reviewed

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

Williams Turpin, Sun-Ho Lee, Juan Antonio Raygoza Garay, Karen L Madsen, Jonathan B Meddings, Larbi Bedrani, Namita Power, Osvaldo Espin-Garcia, Wei Xu, Michelle I Smith, …

Gastroenterology (New York, N.Y. 1943), Vol.159(6), pp.2092-2100.e5

2020-12

DOI: https://doi.org/10.1053/j.gastro.2020.08.005

PMID: 32791132

Abstract

Crohn Disease - epidemiology

Prospective Studies

Follow-Up Studies

Lactulose - metabolism

Humans

Risk Factors

Male

Permeability

Renal Elimination

Young Adult

Lactulose - urine

Lactulose - administration & dosage

Crohn Disease - pathology

Mannitol - administration & dosage

Mannitol - metabolism

Adolescent

Adult

Female

Mannitol - urine

Child

Intestinal Mucosa - pathology

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 ). 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). 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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.120 Inflammatory Bowel Diseases & Infections; 1.120.139 Ulcerative Colitis
Web Of Science research areas: Gastroenterology & Hepatology
ESI research areas: Clinical Medicine

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Title: Increased Intestinal Permeability Is Associated With Later Development of Crohn's Disease
Creators: Williams Turpin - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Sun-Ho Lee - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Juan Antonio Raygoza Garay - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Karen L Madsen - University of Alberta, Edmonton, Alberta, Canada
Jonathan B Meddings - Department of Medicine, Cumming School of Medicine, Calgary, Alberta, Canada
Larbi Bedrani - Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Namita Power - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
Osvaldo Espin-Garcia - Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Wei Xu - Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Michelle I Smith - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
Anne M Griffiths - Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada
Paul Moayyedi - Department of Medicine, McMaster University, Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
Dan Turner - The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
Ernest G Seidman - Inflammatory Bowel Disease Centre, Division of Gastroenterology, McGill University Health Centre, Montréal, Quebec, Canada
A Hillary Steinhart - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada
John K Marshall - Department of Medicine, McMaster University, Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
Kevan Jacobson - Canadian Gastro-Intestinal Epidemiology Consortium, Canada; British Columbia Children's Hospital, Vancouver, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
David Mack - Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada
Hien Huynh - Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
Charles N Bernstein - University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre and, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Manitoba, Winnipeg, Canada
Andrew D Paterson - Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Genetics and Genome Biology, The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
Kenneth Croitoru - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Ken.Croitoru@sinaihealth.ca
Publication Details: Gastroenterology (New York, N.Y. 1943), Vol.159(6), pp.2092-2100.e5
Publisher: United States
Grant note: CMF108031 / CIHR
Language: English
Resource Type: Journal article
PMID: 32791132
Record Identifier: 991031578345202976