한빛사논문
- 조회394
Juan Antonio Raygoza Garay 1,2 ∗, Williams Turpin 2 ∗, Sun-Ho Lee 1,2 ∗, Michelle I. Smith 2, Ashleigh Goethel 2, Anne M. Griffiths 3, Paul Moayyedi 4, Osvaldo Espin-Garcia 5,6, Maria Abreu 7, Guy L. Aumais 8, Charles N. Bernstein 9, Irit A. Biron 10, Maria Cino 1, Colette Deslandres 11, Iris Dotan 10, Wael El-Matary 12, Brian Feagan 13, David S. Guttman 14, Hien Huynh 15, Levinus A. Dieleman 16, Jeffrey S. Hyams 17, Kevan Jacobson 18, David Mack 19, John K. Marshall 4, Anthony Otley 20, Remo Panaccione 21, Mark Ropeleski 22, Mark S. Silverberg 1, A. Hillary Steinhart 1, Dan Turner 23, Baruch Yerushalmi 24, Andrew D. Paterson 5,25, Wei Xu 5,6, The CCC GEM Project Research Consortium 1, Kenneth Croitoru 1,2
1Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
2Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
3Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada
4Department of Medicine, McMaster University, Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
5Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
6Biostatistics Department, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
7Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA
8Hopital Maisonneuve-Rosemont, Montreal, QC, Canada
9University 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
10The Division of Gastroenterology, Rabin Medical Center, Ze'ev Jabotinsky Street 39, Petah-Tikva 4941492, Israel
11CHU Sainte-Justine, Montreal, QC, Canada
12Pediatric Gastroenterology, Max Rady College of Medicine, University of Manitoba, Manitoba, Winnipeg, Canada
13Departments of Medicine, Epidemiology, and Biostatistics University of Western Ontario, London, Ontario, Canada
14Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario
15Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
16Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
17Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children’s Medical Center, Hartford, Connecticut, USA
18British Columbia Children's Hospital, British Columbia Children's Hospital Research Institute
19Division of Gastroenterology, Hepatology & Nutrition, Children’s Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada. University of British Columbia, Vancouver, British Columbia, Canada
20Division of Gastroenterology, Izaak Walton Killam Hospital, Dalhousie University, Halifax, Canada
21University of Calgary, Calgary, AB, Canada
22Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada
23The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
24Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
25Genetics and Genome Biology, The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
∗Contributed equally
Corresponding Authors: Dr. Wei Xu, Dr. Kenneth Croitoru
Abstract
Background and aims: The cause of Crohn's Disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of CD patients have catalogued alterations in the gut microbiome composition; however, these studies fail to distinguish if the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment.
Methods: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S rDNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort.
Results: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio (HR) of 2.24, 95% CI [1.03, 4.84], and a p-value =0.04, using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to five years prior to disease onset (AUC > 0.65). The five most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceace, and Roseburia.
Conclusion: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-06-19)
- 국외 연구진
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