Abstract
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.
Original language | American English |
---|---|
Journal | Gastroenterology |
DOIs | |
State | Accepted/In press - 2023 |
Bibliographical note
Funding Information:Funding This study was supported by grants from Crohn’s and Colitis Canada Grant #CCC-GEMIII, Canadian Institutes of Health Research (CIHR) Grant #CMF108031, and the Leona M. and Harry B. Helmsley Charitable Trust. Williams Turpin is a former recipient of a Postdoctoral Fellowship Research Award from the CIHR Fellowship/Canadian Association of Gastroenterology (CAG)/Ferring Pharmaceuticals Inc. Sun Ho Lee is a former recipient of the Imagine/CIHR/CAG Fellowship Award. Williams Turpin, Sun-Ho Lee, and Juan Antonio Raygoza Garay are recipients of fellowships from the Department of Medicine, Mount Sinai Hospital, Toronto. Kenneth Croitoru is recipient of a Canada Research Chair in Inflammatory Bowel Diseases.
Funding Information:
Funding This study was supported by grants from Crohn's and Colitis Canada Grant #CCC-GEMIII, Canadian Institutes of Health Research (CIHR) Grant #CMF108031, and the Leona M. and Harry B. Helmsley Charitable Trust. Williams Turpin is a former recipient of a Postdoctoral Fellowship Research Award from the CIHR Fellowship/Canadian Association of Gastroenterology (CAG)/Ferring Pharmaceuticals Inc. Sun Ho Lee is a former recipient of the Imagine/CIHR/CAG Fellowship Award. Williams Turpin, Sun-Ho Lee, and Juan Antonio Raygoza Garay are recipients of fellowships from the Department of Medicine, Mount Sinai Hospital, Toronto. Kenneth Croitoru is recipient of a Canada Research Chair in Inflammatory Bowel Diseases.
Publisher Copyright:
© 2023 AGA Institute
Keywords
- Faecalibacterium
- Fecal Calprotectin
- Microbiome
- Preclinical Inflammatory Bowel Disease
- Vitamins B