{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:53:39Z","timestamp":1783479219965,"version":"3.55.0"},"reference-count":47,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"unspecified","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"IBD Centre of BC, Vancouver, BC, Canada"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,2,25]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Inflammatory bowel disease (IBD), including Crohn\u2019s 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>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\u2019s Hospital Research Institute.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06453720\">NCT06453720<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Protocol version<\/jats:title>\n                  <jats:p>2024-06-21, version 3.0.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-094280","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T22:00:52Z","timestamp":1741903252000},"page":"e094280","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Gut microbiome predictors of advanced therapy response in Crohn\u2019s disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06453720","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1528-5498","authenticated-orcid":false,"given":"Cristian Aldo","family":"Massaro","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada"},{"name":"BC Children\u2019s Hospital Research Institute, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Meade","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, NHS North Bristol NHS Trust, Bristol, UK"},{"name":"IBD Centre of BC, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny Laure","family":"Lemari\u00e9","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada"},{"name":"BC Children\u2019s Hospital Research Institute, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurpreet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Bressler","sequence":"additional","affiliation":[{"name":"IBD Centre of BC, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"IBD Centre of BC, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Leung","sequence":"additional","affiliation":[{"name":"IBD Centre of BC, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid-Jane","family":"Williams","sequence":"additional","affiliation":[{"name":"IBD Centre of BC, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genelle","family":"Lunken","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada"},{"name":"BC Children\u2019s Hospital Research Institute, Vancouver, British Columbia, Canada"},{"name":"IBD Centre of BC, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"2025101814115789000_15.3.e094280.1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i1.91"},{"key":"2025101814115789000_15.3.e094280.2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.223263"},{"key":"2025101814115789000_15.3.e094280.3","doi-asserted-by":"crossref","first-page":"913720","DOI":"10.3389\/fphar.2022.913720","article-title":"Distinct alterations of fecal microbiota refer to the efficacy of adalimumab in Crohn\u2019s disease","volume":"13","author":"Chen","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025101814115789000_15.3.e094280.4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/ecco-jcc\/jjx153","article-title":"Characteristics of Faecal Microbiota in Paediatric Crohn\u2019s Disease and Their Dynamic Changes During Infliximab Therapy","volume":"12","author":"Wang","year":"2018","journal-title":"J Crohns Colitis"},{"key":"2025101814115789000_15.3.e094280.5","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa252"},{"key":"2025101814115789000_15.3.e094280.6","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2287073"},{"key":"2025101814115789000_15.3.e094280.7","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2020-042493","article-title":"Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study","volume":"11","author":"Williams","year":"2021","journal-title":"BMJ Open"},{"key":"2025101814115789000_15.3.e094280.8","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.3390\/microorganisms10122507","article-title":"Dietary Fiber Intake and Gut Microbiota in Human Health","volume":"10","author":"Fu","year":"2022","journal-title":"Microorganisms"},{"key":"2025101814115789000_15.3.e094280.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1237-9"},{"key":"2025101814115789000_15.3.e094280.10","doi-asserted-by":"crossref","DOI":"10.1038\/ctg.2017.58","article-title":"Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease","volume":"9","author":"Moustafa","year":"2018","journal-title":"Clin Transl Gastroenterol"},{"key":"2025101814115789000_15.3.e094280.11","doi-asserted-by":"crossref","DOI":"10.1128\/msystems.00188-17","article-title":"Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction","volume":"3","author":"Zhou","year":"2018","journal-title":"mSystems"},{"key":"2025101814115789000_15.3.e094280.12","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1080\/00365521.2020.1829031","article-title":"eHealth: Disease activity measures are related to the faecal gut microbiota in adult patients with ulcerative colitis","volume":"55","author":"Ankersen","year":"2020","journal-title":"Scand J Gastroenterol"},{"key":"2025101814115789000_15.3.e094280.13","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1093\/ecco-jcc\/jjz077","article-title":"Anti-inflammatory Gut Microbial Pathways Are Decreased During Crohn\u2019s Disease Exacerbations","volume":"13","author":"Klaassen","year":"2019","journal-title":"J Crohns Colitis"},{"key":"2025101814115789000_15.3.e094280.14","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16086"},{"key":"2025101814115789000_15.3.e094280.15","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000136"},{"key":"2025101814115789000_15.3.e094280.16","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-012-0605-0"},{"key":"2025101814115789000_15.3.e094280.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.09.008"},{"key":"2025101814115789000_15.3.e094280.18","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.07.025"},{"key":"2025101814115789000_15.3.e094280.19","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-10450-2","article-title":"Microbial changes in stool, saliva, serum, and urine before and after anti-TNF-\u03b1 therapy in patients with inflammatory bowel diseases","volume":"12","author":"Park","year":"2022","journal-title":"Sci Rep"},{"key":"2025101814115789000_15.3.e094280.20","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2020.1803396"},{"key":"2025101814115789000_15.3.e094280.21","doi-asserted-by":"publisher","DOI":"10.1053\/J.GASTRO.2019.11.294"},{"key":"2025101814115789000_15.3.e094280.22","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-40182-9","article-title":"Effects of bowel preparation on the human gut microbiome and metabolome","volume":"9","author":"Nagata","year":"2019","journal-title":"Sci Rep"},{"key":"2025101814115789000_15.3.e094280.23","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-321106"},{"key":"2025101814115789000_15.3.e094280.24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4103\/1319-3767.182455","article-title":"Implementation of the simple endoscopic activity score in crohn\u2019s disease","volume":"22","author":"Koutroumpakis","year":"2016","journal-title":"Saudi J Gastroenterol"},{"key":"2025101814115789000_15.3.e094280.25","doi-asserted-by":"crossref","first-page":"S","DOI":"10.1016\/S0016-5085(15)30642-9","article-title":"1025 Development of the Modified Harvey-Bradshaw Index (mHBI) Score, HBI-PRO, to Assess Disease Activity in Crohn\u2019s Disease","volume":"148","author":"Zittan","year":"2015","journal-title":"Gastroenterology"},{"key":"2025101814115789000_15.3.e094280.26","unstructured":"Inflammatory Bowel Disease Questionnaire (IBDQ) . Research & innovation. Available: https:\/\/research.mcmaster.ca\/industry-investors\/technologies-available-for-licensing\/quality-of-life-questionnaires-tools\/copyright-97-020\/ [Accessed 17 Sep 2024]."},{"key":"2025101814115789000_15.3.e094280.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.04.010"},{"key":"2025101814115789000_15.3.e094280.28","doi-asserted-by":"crossref","unstructured":"Stinson LF , Keelan JA , Payne MS . Profiling bacterial communities in low biomass samples: pitfalls and considerations. Microbiol Aust 2019. doi:10.1071\/MA19053","DOI":"10.1071\/MA19053"},{"key":"2025101814115789000_15.3.e094280.29","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1093\/ecco-jcc\/jjaa257","article-title":"Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD","volume":"15","author":"Poletti","year":"2021","journal-title":"J Crohns Colitis"},{"key":"2025101814115789000_15.3.e094280.30","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.10"},{"key":"2025101814115789000_15.3.e094280.31","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2746"},{"key":"2025101814115789000_15.3.e094280.32","doi-asserted-by":"crossref","DOI":"10.3390\/nu16020280","article-title":"Nutritional Biomarkers for the Prediction of Response to Anti-TNF-\u03b1 Therapy in Crohn\u2019s Disease: New Tools for New Approaches","volume":"16","author":"Rizzello","year":"2024","journal-title":"Nutrients"},{"key":"2025101814115789000_15.3.e094280.33","unstructured":"MetaPhlAn4 \u2013 the huttenhower lab. Available: https:\/\/huttenhower.sph.harvard.edu\/metaphlan\/ [Accessed 17 Sep 2024]."},{"key":"2025101814115789000_15.3.e094280.34","unstructured":"Humann2 \u2013 the huttenhower lab. Available: https:\/\/huttenhower.sph.harvard.edu\/humann2\/ [Accessed 17 Sep 2024]."},{"key":"2025101814115789000_15.3.e094280.35","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa039"},{"key":"2025101814115789000_15.3.e094280.36","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-07841-3","article-title":"Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response","volume":"10","author":"Haberman","year":"2019","journal-title":"Nat Commun"},{"key":"2025101814115789000_15.3.e094280.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0308-z"},{"key":"2025101814115789000_15.3.e094280.38","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms8030438","article-title":"The Interplay between Mucosal Microbiota Composition and Host Gene-Expression is Linked with Infliximab Response in Inflammatory Bowel Diseases","volume":"8","author":"Dovrolis","year":"2020","journal-title":"Microorganisms"},{"key":"2025101814115789000_15.3.e094280.39","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izaa216"},{"key":"2025101814115789000_15.3.e094280.40","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2023.101050","article-title":"Integrative multi-omics deciphers the spatial characteristics of host-gut microbiota interactions in Crohn\u2019s disease","volume":"4","author":"Gao","year":"2023","journal-title":"Cell Rep Med"},{"key":"2025101814115789000_15.3.e094280.41","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310746"},{"key":"2025101814115789000_15.3.e094280.42","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41564-021-00983-z","article-title":"Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn\u2019s disease","volume":"6","author":"Doron","year":"2021","journal-title":"Nat Microbiol"},{"key":"2025101814115789000_15.3.e094280.43","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.cell.2021.01.016","article-title":"Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies","volume":"184","author":"Doron","year":"2021","journal-title":"Cell"},{"key":"2025101814115789000_15.3.e094280.44","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308341"},{"key":"2025101814115789000_15.3.e094280.45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2147\/CEG.S371965","article-title":"Ethnicity Associated Microbial and Metabonomic Profiling in Newly Diagnosed Ulcerative Colitis","volume":"15","author":"Misra","year":"2022","journal-title":"Clin Exp Gastroenterol"},{"key":"2025101814115789000_15.3.e094280.46","doi-asserted-by":"crossref","DOI":"10.3390\/nu14245236","article-title":"Comparison between Self-Completed and Interviewer-Administered 24-Hour Dietary Recalls in Cancer Survivors: Sampling Bias and Differential Reporting","volume":"14","author":"Conway","year":"2022","journal-title":"Nutrients"},{"key":"2025101814115789000_15.3.e094280.47","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.ajcnut.2023.01.017","article-title":"Impact of a farmers\u2019 market healthy food subsidy on the diet quality of adults with low incomes in British Columbia, Canada: a pragmatic randomized controlled trial","volume":"117","author":"Aktary","year":"2023","journal-title":"Am J Clin Nutr"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-094280","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T21:12:04Z","timestamp":1760821924000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-094280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,13]]},"published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1136\/bmjopen-2024-094280"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-094280","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]}}}