After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence

Cristian Hernández-Rocha¹, Williams Turpin², Krzysztof Borowski², Joanne M Stempak², Ksenija Sabic³, Kyle Gettler³, Christopher Tastad³, Colleen Chasteau³, Ujunwa Korie³, Mary Hanna⁴, Abdul Khan⁴, Emebet Mengesha⁴, Alain Bitton⁵, Marc B Schwartz⁶, Arthur Barrie⁶, Lisa W Datta⁷, Mark Lazarev⁷, Steven R Brant⁸, John D Rioux⁹, Dermot P B McGovern⁴, Richard H Duerr¹⁰, L Phil Schumm¹¹, Judy H Cho³, Mark S Silverberg¹²

Affiliations

¹ Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica of Chile, Santiago, Chile.
² Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
³ Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
⁴ F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California.
⁵ Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada.
⁶ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁷ Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁸ Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School and the Crohn's and Colitis Center of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey; Department of Genetics and The Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
⁹ Research Centre, Montreal Heart Institute, Montréal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
¹⁰ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania.
¹¹ Biostatistics Laboratory & Research Computing Group, Department of Public Health Sciences, University of Chicago, Chicago, Illinois.
¹² Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: mark.silverberg@sinaihealth.ca.

PMID: 38969076
PMCID: PMC11979954 (available on 2026-03-01)
DOI: 10.1016/j.cgh.2024.06.022

Multicenter Study

After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence

Cristian Hernández-Rocha et al. Clin Gastroenterol Hepatol. 2025 Mar.

. 2025 Mar;23(4):612-620.e10.

doi: 10.1016/j.cgh.2024.06.022. Epub 2024 Jul 4.

Authors

Affiliations

¹ Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica of Chile, Santiago, Chile.
² Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
³ Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
⁴ F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California.
⁵ Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada.
⁶ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁷ Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁸ Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School and the Crohn's and Colitis Center of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey; Department of Genetics and The Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
⁹ Research Centre, Montreal Heart Institute, Montréal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
¹⁰ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania.
¹¹ Biostatistics Laboratory & Research Computing Group, Department of Public Health Sciences, University of Chicago, Chicago, Illinois.
¹² Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: mark.silverberg@sinaihealth.ca.

PMID: 38969076
PMCID: PMC11979954 (available on 2026-03-01)
DOI: 10.1016/j.cgh.2024.06.022

Abstract

Background & aims: Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease.

Methods: Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence.

Results: A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn's disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features.

Conclusions: Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

Keywords: Crohn’s Disease; Disease Recurrence; Microbiota; Prediction.

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Conflict of interest statement

Conflict of Interest

The authors have no conflicts of interest to declare.

References

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After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence

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After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence

Authors

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Conflict of interest statement

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