Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer

Associations between the gut microbiome and colorectal cancer (CRC) have been uncovered, but larger and more diverse studies are needed to assess their potential clinical use. We expanded upon 12 metagenomic datasets of patients with CRC (n = 930), adenomas (n = 210) and healthy control individuals (n = 976; total n = 2,116) with 6 new cohorts (n = 1,625) providing granular information on cancer stage and the anatomic location of tumors. We improved CRC prediction accuracy based solely on gut metagenomics (average area under the curve = 0.85) and highlighted the contribution of 19 newly profiled species and distinct Fusobacterium nucleatum clades. Specific gut species distinguish left-sided versus right-sided CRC (area under the curve = 0.66) with an enrichment of oral-typical microbes. We identified strain-specific CRC signatures with the commensal Ruminococcus bicirculans and Faecalibacterium prausnitzii showing subclades associated with late-stage CRC. Our analysis confirms that the microbiome can be a clinical target for CRC screening and characterizes it as a biomarker for CRC progression.

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Publication Details

Journal
Nature Medicine
Published
2025-06-03
DOI
https://doi.org/10.1038/s41591-025-03693-9
Citations
45
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
36.27
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article

Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer

Eva Budínská, Pavel Vodička, Gianmarco Piccinno, Curtis Huttenhower et al.
45 citations
Nature Medicine
Gut microbiota and health
36.27
article

Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer

Eva Budínská, Pavel Vodička, Gianmarco Piccinno, Curtis Huttenhower, Gloria Fackelmann, Paolo Manghi, Václav Liška, Mingyang Song, Mario Trompetto, Francesco Asnicar, Federica Marmorino, Federica Pinto, Aitor Blanco‐Míguez, Sonia Tarallo, Veronika Vymetalkova, Lisa Derosa, Vlad Popovici, Nazim Arda Keles, Beatrix Bencsiková, Francesca Cordero, Alessio Naccarati, Nicola Segata, Bilge Güvenç Tuna, Andrew T. Chan, Vitor Heidrich, Tomáš Hucl, Laurence Zitvogel, Elisa Piperni, Andrew Maltez Thomas, Chiara Cremolini, Andrew R. Ghazi, Giulio Ferrero, Michal Punčochář, Federica Armanini, Barbara Pardini, Martina Čarnogurská, Yan Yan, Long H. Nguyen, Kelsey N. Thompson, Katarina Mladenović
article en
45 citations

Abstract

Associations between the gut microbiome and colorectal cancer (CRC) have been uncovered, but larger and more diverse studies are needed to assess their potential clinical use. We expanded upon 12 metagenomic datasets of patients with CRC (n = 930), adenomas (n = 210) and healthy control individuals (n = 976; total n = 2,116) with 6 new cohorts (n = 1,625) providing granular information on cancer stage and the anatomic location of tumors. We improved CRC prediction accuracy based solely on gut metagenomics (average area under the curve = 0.85) and highlighted the contribution of 19 newly profiled species and distinct Fusobacterium nucleatum clades. Specific gut species distinguish left-sided versus right-sided CRC (area under the curve = 0.66) with an enrichment of oral-typical microbes. We identified strain-specific CRC signatures with the commensal Ruminococcus bicirculans and Faecalibacterium prausnitzii showing subclades associated with late-stage CRC. Our analysis confirms that the microbiome can be a clinical target for CRC screening and characterizes it as a biomarker for CRC progression.

Nature MedicineVol. 31(7)
Yeditepe University (TR), Broad Institute (US), University of Pisa (IT), Harvard University (US), Inserm (FR), University of Trento (IT), Charles University (CZ), Masaryk University (CZ), Université Paris-Saclay (FR), Institut Gustave Roussy (FR), Massachusetts General Hospital (US), La Ligue Contre le Cancer (FR), Masaryk Memorial Cancer Institute (CZ), Italian institute for Genomic Medicine (IT), Institute of Clinical and Experimental Medicine (CZ), Czech Academy of Sciences, Institute of Experimental Medicine (CZ), Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers (FR), Candiolo Cancer Institute (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University of Turin (IT), European Institute of Oncology (IT)
Openalex Percentile: Top 0%
Gut microbiota and health
36.27
DOIOpen Access PDFOpenAlex
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