Piccinno Gianmarco, Thompson Kelsey N, Manghi Paolo, Ghazi Andrew R, Thomas Andrew Maltez, Blanco-Míguez Aitor, Asnicar Francesco, Mladenovic Katarina, Pinto Federica, Armanini Federica, Punčochář 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, Bencsiková 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, Budinska Eva, Segata Nicola
Department CIBIO, University of Trento, Trento, Italy.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Nat Med. 2025 Jun 3. doi: 10.1038/s41591-025-03693-9.
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.
肠道微生物群与结直肠癌（CRC）之间的关联已被发现，但需要更大规模和更多样化的研究来评估它们的潜在临床应用价值。我们扩展了12个结直肠癌患者（n = 930）、腺瘤患者（n = 210）和健康对照个体（n = 976；总计n = 2,116）的宏基因组数据集，新增了6个队列（n = 1,625），这些队列提供了关于癌症分期和肿瘤解剖位置的详细信息。我们仅基于肠道宏基因组学提高了结直肠癌预测准确性（曲线下面积平均值 = 0.85），并突出了19个新分析的物种和不同核梭杆菌分支的贡献。特定的肠道物种可区分左侧与右侧结直肠癌（曲线下面积 = 0.66），且口腔典型微生物有所富集。我们通过共生双环瘤胃球菌和普拉梭菌鉴定出菌株特异性的结直肠癌特征，这些菌株显示出与晚期结直肠癌相关的亚分支。我们的分析证实，微生物群可成为结直肠癌筛查的临床靶点，并将其表征为结直肠癌进展的生物标志物。
