Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death globally. Growing evidence links gut microbiota dysbiosis to CRC, with several reviews reporting consistent microbial alterations in CRC patients that may serve as non-invasive biomarkers. However, findings vary across studies, and consensus on key microbial taxa is lacking. This umbrella review aims to clarify: (1) the association between gut microbiome composition and CRC development/progression, (2) specific microbial taxa linked to CRC risk, (3) the role of microbiome diversity in CRC outcomes and (4) potential microbial biomarkers for diagnosis, prognosis and treatment response.

This umbrella review will follow the Joanna Briggs Institute (JBI) Umbrella Review Guidelines and adhere to the Preferred Reporting Items for Overviews of Reviews. A comprehensive search will be conducted across MEDLINE (PubMed), Embase, CINAHL and key systematic review databases, including the Cochrane Database, JBI Evidence Synthesis and Database of Abstracts of Reviews of Effects, without language restrictions. The search strategy will use a combination of Medical Subject Headings terms and free-text keywords with Boolean operators. The review questions were developed using the Population, Concept and Context framework. Only high-quality (as determined by the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses), peer-reviewed quantitative systematic reviews with or without meta-analyses will be included. Overall effect estimates extracted from systematic reviews, with the number of studies that inform the outcome, will be presented.

No ethical approval is required since the work is carried out on published documents. Findings of this review will be disseminated among relevant stakeholders through multiple scientific avenues, including presentations at both national and international forums and manuscript publication in an open-access journal.

PROSPERO 2025 CRD420251035257. Available from:

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251035257.