. 2023 Sep;165(3):670-681.

doi: 10.1053/j.gastro.2023.05.032. Epub 2023 May 30.

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives

Juan Antonio Raygoza Garay¹, Williams Turpin², Sun-Ho Lee¹, Michelle I Smith², Ashleigh Goethel², Anne M Griffiths³, Paul Moayyedi⁴, Osvaldo Espin-Garcia⁵, Maria Abreu⁶, Guy L Aumais⁷, Charles N Bernstein⁸, Irit A Biron⁹, Maria Cino¹⁰, Colette Deslandres¹¹, Iris Dotan⁹, Wael El-Matary¹², Brian Feagan¹³, David S Guttman¹⁴, Hien Huynh¹⁵, Levinus A Dieleman¹⁶, Jeffrey S Hyams¹⁷, Kevan Jacobson¹⁸, David Mack¹⁹, John K Marshall⁴, Anthony Otley²⁰, Remo Panaccione²¹, Mark Ropeleski²², Mark S Silverberg¹⁰, A Hillary Steinhart¹⁰, Dan Turner²³, Baruch Yerushalmi²⁴, Andrew D Paterson²⁵, Wei Xu²⁶; CCC GEM Project Research Consortium; Kenneth Croitoru⁴⁸

Collaborators, Affiliations

Collaborators

CCC GEM Project Research Consortium:
Maria Abreu⁶, Paul Beck²⁷, Charles Bernstein²⁸, Kenneth Croitoru²⁹, Levinus A Dieleman¹⁶, Brian Feagan³⁰, Anne Griffiths³, David Guttman³¹, Kevan Jacobson¹⁸, Gilaad Kaplan²⁷, Denis O Krause³², Karen Madsen³³, John Marshall⁴, Paul Moayyedi⁴, Mark Ropeleski²², Ernest Seidman³⁴, Mark Silverberg¹⁰, Scott Snapper³⁵, Andy Stadnyk³⁶, Hillary Steinhart¹⁰, Michael Surette³⁷, Dan Turner²³, Thomas Walters³⁸, Bruce Vallance³⁹, Guy Aumais⁴⁰, Alain Bitton³⁴, Maria Cino¹⁰, Jeff Critch⁴¹, Lee Denson⁴², Colette Deslandres⁴³, Wael El-Matary¹², Hans Herfarth⁴⁴, Peter Higgins⁴⁵, Hien Huynh¹⁵, Jeffrey S Hyams¹⁷, David Mack⁴⁶, Jerry McGrath⁴⁷, Anthony Otley²⁰, Remo Panancionne²¹

Affiliations

¹ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
² Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
³ Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
⁵ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Biostatistics Department, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
⁶ Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
⁷ Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
⁸ Inflammatory Bowel Disease Clinical and Research Center and Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Manitoba, Winnipeg, Canada.
⁹ Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.
¹⁰ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Hepatology and Pediatric Nutrition, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
¹² Pediatric Gastroenterology, Max Rady College of Medicine, University of Manitoba, Manitoba, Winnipeg, Canada.
¹³ Departments of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
¹⁴ Center for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
¹⁶ Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
¹⁷ Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut.
¹⁸ Research Institute, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
¹⁹ Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada.
²⁰ Division of Gastroenterology, Izaak Walton Killam Hospital, Dalhousie University, Halifax, Nova Scotia, Canada.
²¹ Inflammatory Bowel Disease Unit, University of Calgary, Calgary, Alberta, Canada.
²² Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
²³ The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
²⁴ Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
²⁵ 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.
²⁶ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Biostatistics Department, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. Electronic address: wei.xu@uhnres.utoronto.ca.
²⁷ Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁸ 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.
²⁹ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
³⁰ Departments of Medicine, Epidemiology, and Biostatistics, University of Western Ontario, London, Ontario, Canada.
³¹ Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario, Canada.
³² Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
³³ Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
³⁴ Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.
³⁵ Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
³⁶ Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.
³⁷ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
³⁸ Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
³⁹ BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
⁴⁰ Biostatistics Department, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
⁴¹ Janeway Children's Health and Rehabilitation Centre and Department of Pediatrics, Memorial University, St. John's, Newfoundland, Canada.
⁴² Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
⁴³ Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
⁴⁴ Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
⁴⁵ Division of Gastroenterology & Hepatology, University of Michigan, Ann Arbor, Michigan.
⁴⁶ Division 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.
⁴⁷ Provincial Medical Genetics Program, Eastern Health, St. John's, Newfoundland, Canada.
⁴⁸ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: ken.croitoru@sinaihealth.ca.

PMID: 37263307
DOI: 10.1053/j.gastro.2023.05.032

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives

Juan Antonio Raygoza Garay et al. Gastroenterology. 2023 Sep.

. 2023 Sep;165(3):670-681.

doi: 10.1053/j.gastro.2023.05.032. Epub 2023 May 30.

Authors

Collaborators

CCC GEM Project Research Consortium:
Maria Abreu⁶, Paul Beck²⁷, Charles Bernstein²⁸, Kenneth Croitoru²⁹, Levinus A Dieleman¹⁶, Brian Feagan³⁰, Anne Griffiths³, David Guttman³¹, Kevan Jacobson¹⁸, Gilaad Kaplan²⁷, Denis O Krause³², Karen Madsen³³, John Marshall⁴, Paul Moayyedi⁴, Mark Ropeleski²², Ernest Seidman³⁴, Mark Silverberg¹⁰, Scott Snapper³⁵, Andy Stadnyk³⁶, Hillary Steinhart¹⁰, Michael Surette³⁷, Dan Turner²³, Thomas Walters³⁸, Bruce Vallance³⁹, Guy Aumais⁴⁰, Alain Bitton³⁴, Maria Cino¹⁰, Jeff Critch⁴¹, Lee Denson⁴², Colette Deslandres⁴³, Wael El-Matary¹², Hans Herfarth⁴⁴, Peter Higgins⁴⁵, Hien Huynh¹⁵, Jeffrey S Hyams¹⁷, David Mack⁴⁶, Jerry McGrath⁴⁷, Anthony Otley²⁰, Remo Panancionne²¹

Affiliations

¹ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
² Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
³ Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
⁵ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Biostatistics Department, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
⁶ Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
⁷ Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
⁸ Inflammatory Bowel Disease Clinical and Research Center and Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Manitoba, Winnipeg, Canada.
⁹ Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.
¹⁰ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Hepatology and Pediatric Nutrition, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
¹² Pediatric Gastroenterology, Max Rady College of Medicine, University of Manitoba, Manitoba, Winnipeg, Canada.
¹³ Departments of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
¹⁴ Center for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
¹⁶ Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
¹⁷ Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut.
¹⁸ Research Institute, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
¹⁹ Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada.
²⁰ Division of Gastroenterology, Izaak Walton Killam Hospital, Dalhousie University, Halifax, Nova Scotia, Canada.
²¹ Inflammatory Bowel Disease Unit, University of Calgary, Calgary, Alberta, Canada.
²² Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
²³ The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
²⁴ Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
²⁵ 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.
²⁶ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Biostatistics Department, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. Electronic address: wei.xu@uhnres.utoronto.ca.
²⁷ Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁸ 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.
²⁹ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
³⁰ Departments of Medicine, Epidemiology, and Biostatistics, University of Western Ontario, London, Ontario, Canada.
³¹ Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario, Canada.
³² Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
³³ Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
³⁴ Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.
³⁵ Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
³⁶ Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.
³⁷ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
³⁸ Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
³⁹ BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
⁴⁰ Biostatistics Department, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
⁴¹ Janeway Children's Health and Rehabilitation Centre and Department of Pediatrics, Memorial University, St. John's, Newfoundland, Canada.
⁴² Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
⁴³ Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
⁴⁴ Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
⁴⁵ Division of Gastroenterology & Hepatology, University of Michigan, Ann Arbor, Michigan.
⁴⁶ Division 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.
⁴⁷ Provincial Medical Genetics Program, Eastern Health, St. John's, Newfoundland, Canada.
⁴⁸ Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: ken.croitoru@sinaihealth.ca.

PMID: 37263307
DOI: 10.1053/j.gastro.2023.05.032

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.

Keywords: Faecalibacterium; Fecal Calprotectin; Microbiome; Preclinical Inflammatory Bowel Disease; Vitamins B.

PubMed Disclaimer

Comment in

Toward the Understanding of Altered Gut Microbiome in Crohn's Disease: Cause or Consequence.
Gao S, Zhu R, Zhu L. Gao S, et al. Gastroenterology. 2024 Feb;166(2):353-354. doi: 10.1053/j.gastro.2023.06.015. Epub 2023 Jun 24. Gastroenterology. 2024. PMID: 37356671 No abstract available.
Investigating the Causal Relationship Between Gut Microbiota and Crohn's Disease: A Mendelian Randomization Study.
Li Z, Chen Y, Ke H. Li Z, et al. Gastroenterology. 2024 Feb;166(2):354-355. doi: 10.1053/j.gastro.2023.08.047. Epub 2023 Sep 9. Gastroenterology. 2024. PMID: 37678500 No abstract available.
Gut dysbiosis in Crohn's disease: Never so close to solving the chicken-and-egg enigma: Commentary to "Gut microbiome composition is associated with future onset of Crohn's disease in healthy first-degree relatives, by Raygoza Garay JA et al., Gastroenterology 2023".
Grellier N, Sokol H, Seksik P. Grellier N, et al. Clin Res Hepatol Gastroenterol. 2024 Feb;48(2):102272. doi: 10.1016/j.clinre.2023.102272. Epub 2023 Dec 23. Clin Res Hepatol Gastroenterol. 2024. PMID: 38145785

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

CMF108031/CIHR/Canada

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives

Collaborators

Affiliations

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives

Authors

Collaborators

Affiliations

Abstract

Comment in

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases