Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada

Introduction Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis, is characterised by chronic and relapsing inflammation of the gastrointestinal tract, leading to significant morbidity and reduced quality of life. The global rise in IBD incidence is driven by a co...

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Main Authors: Greg Rosenfeld, Susanna Meade, Yvette Leung, Astrid-Jane Williams, Gurpreet Kaur, Brian Bressler, Cristian Aldo Massaro, Fanny Laure Lemarié, Genelle Lunken
Format: Article
Language:English
Published: BMJ Publishing Group 2025-03-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/3/e094280.full
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author Greg Rosenfeld
Susanna Meade
Yvette Leung
Astrid-Jane Williams
Gurpreet Kaur
Brian Bressler
Cristian Aldo Massaro
Fanny Laure Lemarié
Genelle Lunken
author_facet Greg Rosenfeld
Susanna Meade
Yvette Leung
Astrid-Jane Williams
Gurpreet Kaur
Brian Bressler
Cristian Aldo Massaro
Fanny Laure Lemarié
Genelle Lunken
author_sort Greg Rosenfeld
collection DOAJ
description Introduction Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis, is characterised by chronic and relapsing inflammation of the gastrointestinal tract, leading to significant morbidity and reduced quality of life. The global rise in IBD incidence is driven by a complex interplay of genetic, environmental, dietary and microbiome-related factors. Despite advancements in treatment, such as biologics, response rates remain variable, highlighting the need for personalised approaches. Recent research suggests that specific microbiome signatures may serve as biomarkers for predicting therapeutic efficacy, offering a potential tool for optimising treatment strategies in CD. The aim of the Optimising IBD Patient Treatment with Integrated Microbiome Investigation for Specialised Therapeutics (OPTIMIST) study is to evaluate microbiome profiles across various sample types in a Canadian CD cohort starting or already on advanced therapy, with the goal of developing predictive models for personalised therapeutics.Methods and analysis This study is a two-phase, longitudinal, prospective observational pilot study conducted in British Columbia, Canada, involving both CD patients and non-IBD controls. Phase 1 focuses on baseline microbiome differences across participant cohorts through cross-sectional analysis. Phase 2 follows participants over 12 months to assess microbiome changes and their association with treatment response. Stool samples, intestinal biopsies from the left colon, right colon and ileum, as well as mucosal wash samples from the proximal part of the distal colon, will undergo metagenomics, metaproteomics and metabolomics analyses to explore compositional and functional differences. Data will be analysed using alpha and beta diversity metrics, differential abundance analyses and multivariate analyses to identify microbiome-based predictors of therapeutic response.Ethics and dissemination Ethical approval was received by the Research Ethics Board (REB) of University of British Columbia-Providence Healthcare (UBC-PHC) with a REB number H23-02927. All amendments to the protocol are reported and adapted based on the requirements of the REB. The results of this study will be submitted to peer-reviewed journals and will be communicated in editorials/articles by the IBD Centre of BC and BC Children’s Hospital Research Institute.Trial registration number NCT06453720.Protocol version 2024-06-21, version 3.0.
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spelling doaj-art-21e01b7b17a646d786cf1d6ebfab70242025-08-20T02:41:48ZengBMJ Publishing GroupBMJ Open2044-60552025-03-0115310.1136/bmjopen-2024-094280Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in CanadaGreg Rosenfeld0Susanna Meade1Yvette Leung2Astrid-Jane Williams3Gurpreet Kaur4Brian Bressler5Cristian Aldo Massaro6Fanny Laure Lemarié7Genelle Lunken8IBD Centre of BC, Vancouver, British Columbia, Canada2 Department of Gastroenterology, Guy`s and Saint Thomas` NHS Foundation Trust, London, UK2 Department of Medicine, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Gastroenterology, Liverpool Hospital, Liverpool, New South Wales, AustraliaSchool of Nursing and Midwifery, University of Worcester, Worcester, Worcestershire, UKDepartment of Medicine, The University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pediatrics, The University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pediatrics, The University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Pediatrics, The University of British Columbia, Vancouver, British Columbia, CanadaIntroduction Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis, is characterised by chronic and relapsing inflammation of the gastrointestinal tract, leading to significant morbidity and reduced quality of life. The global rise in IBD incidence is driven by a complex interplay of genetic, environmental, dietary and microbiome-related factors. Despite advancements in treatment, such as biologics, response rates remain variable, highlighting the need for personalised approaches. Recent research suggests that specific microbiome signatures may serve as biomarkers for predicting therapeutic efficacy, offering a potential tool for optimising treatment strategies in CD. The aim of the Optimising IBD Patient Treatment with Integrated Microbiome Investigation for Specialised Therapeutics (OPTIMIST) study is to evaluate microbiome profiles across various sample types in a Canadian CD cohort starting or already on advanced therapy, with the goal of developing predictive models for personalised therapeutics.Methods and analysis This study is a two-phase, longitudinal, prospective observational pilot study conducted in British Columbia, Canada, involving both CD patients and non-IBD controls. Phase 1 focuses on baseline microbiome differences across participant cohorts through cross-sectional analysis. Phase 2 follows participants over 12 months to assess microbiome changes and their association with treatment response. Stool samples, intestinal biopsies from the left colon, right colon and ileum, as well as mucosal wash samples from the proximal part of the distal colon, will undergo metagenomics, metaproteomics and metabolomics analyses to explore compositional and functional differences. Data will be analysed using alpha and beta diversity metrics, differential abundance analyses and multivariate analyses to identify microbiome-based predictors of therapeutic response.Ethics and dissemination Ethical approval was received by the Research Ethics Board (REB) of University of British Columbia-Providence Healthcare (UBC-PHC) with a REB number H23-02927. All amendments to the protocol are reported and adapted based on the requirements of the REB. The results of this study will be submitted to peer-reviewed journals and will be communicated in editorials/articles by the IBD Centre of BC and BC Children’s Hospital Research Institute.Trial registration number NCT06453720.Protocol version 2024-06-21, version 3.0.https://bmjopen.bmj.com/content/15/3/e094280.full
spellingShingle Greg Rosenfeld
Susanna Meade
Yvette Leung
Astrid-Jane Williams
Gurpreet Kaur
Brian Bressler
Cristian Aldo Massaro
Fanny Laure Lemarié
Genelle Lunken
Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada
BMJ Open
title Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada
title_full Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada
title_fullStr Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada
title_full_unstemmed Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada
title_short Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada
title_sort gut microbiome predictors of advanced therapy response in crohn s disease protocol for the optimist prospective longitudinal observational pilot study in canada
url https://bmjopen.bmj.com/content/15/3/e094280.full
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