Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.
Faecalibacterium
Fecal Calprotectin
Microbiome
Preclinical Inflammatory Bowel Disease
Vitamins B
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
16
03
2023
revised:
01
05
2023
accepted:
08
05
2023
medline:
22
8
2023
pubmed:
2
6
2023
entrez:
1
6
2023
Statut:
ppublish
Résumé
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 patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment. 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 ribosomal RNA 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. In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .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 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia. 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.
Sections du résumé
BACKGROUND & 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 patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether 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 ribosomal RNA 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 of 2.24 (95% confidence interval, 1.03-4.84; P = .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 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, 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.
Identifiants
pubmed: 37263307
pii: S0016-5085(23)00805-3
doi: 10.1053/j.gastro.2023.05.032
pii:
doi:
Substances chimiques
Leukocyte L1 Antigen Complex
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
670-681Subventions
Organisme : CIHR
ID : CMF108031
Pays : Canada
Investigateurs
Maria Abreu
(M)
Paul Beck
(P)
Charles Bernstein
(C)
Kenneth Croitoru
(K)
Levinus A Dieleman
(LA)
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)
Jeffrey S Hyams
(JS)
David Mack
(D)
Jerry McGrath
(J)
Anthony Otley
(A)
Remo Panancionne
(R)
Informations de copyright
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