Gut microbiome predictors of advanced therapy response in Crohn’s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.012 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.007 | 0.002 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.016 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".