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

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Authors

PICCINNO Gianmarco THOMPSON Kelsey N. MANGHI Paolo GHAZI Andrew R. THOMAS Andrew Maltez BLANCO-MIGUEZ Aitor ASNICAR Francesco MLADENOVIC Katarina PINTO Federica ARMANINI Federica PUNCOCHAR Michal PIPERNI Elisa HEIDRICH Vitor FACKELMANN Gloria FERRERO Giulio TARALLO Sonia NGUYEN Long H. YAN Yan KELES Nazim A. TUNA Bilge G. VYMETALKOVA Veronika TROMPETTO Mario LISKA Vaclav HUCL Tomas VODICKA Pavel BENCSIKOVA Beatrix ČARNOGURSKÁ Martina POPOVICI Vlad MARMORINO Federica CREMOLINI Chiara PARDINI Barbara CORDERO Francesca SONG Mingyang CHAN Andrew T. DEROSA Lisa ZITVOGEL Laurence HUTTENHOWER Curtis NACCARATI Alessio BUDINSKÁ Eva SEGATA Nicola

Year of publication 2025
Type Article in Periodical
Magazine / Source Nature Medicine
MU Faculty or unit

Faculty of Science

Citation
web https://www.nature.com/articles/s41591-025-03693-9
Doi http://dx.doi.org/10.1038/s41591-025-03693-9
Keywords GUT MICROBIOTA; ASSOCIATION; RISK
Attached files
Description 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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