Nature Medicine ( IF 58.7 ) Pub Date : 2025-06-03 , DOI: 10.1038/s41591-025-03693-9
Gianmarco Piccinno, Kelsey N. Thompson, Paolo Manghi, Andrew R. Ghazi, Andrew Maltez Thomas, Aitor Blanco-Míguez, Francesco Asnicar, Katarina Mladenovic, Federica Pinto, Federica Armanini, Michal Punčochář, Elisa Piperni, Vitor Heidrich, Gloria Fackelmann, Giulio Ferrero, Sonia Tarallo, Long H. Nguyen, Yan Yan, Nazim A. Keles, Bilge G. Tuna, Veronika Vymetalkova, Mario Trompetto, Vaclav Liska, Tomas Hucl, Pavel Vodicka, Beatrix Bencsiková, Martina Čarnogurská, Vlad Popovici, Federica Marmorino, Chiara Cremolini, Barbara Pardini, Francesca Cordero, Mingyang Song, Andrew T. Chan, Lisa Derosa, Laurence Zitvogel, Curtis Huttenhower, Alessio Naccarati, Eva Budinska, Nicola Segata
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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‚Äâ=‚Äâ930), adenomas (n‚Äâ=‚Äâ210) and healthy control individuals (n‚Äâ=‚Äâ976; total n‚Äâ=‚Äâ2,116) with 6 new cohorts (n‚Äâ=‚Äâ1,625) 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‚Äâ=‚Äâ0.85) 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‚Äâ=‚Äâ0.66) 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.
中文翻译:

对来自 18 个队列的 3,741 个粪便宏基因组进行结直肠癌跨分期和菌株水平可重复微生物生物标志物的汇总分析
肠道微生物组与结直肠癌 (CRC) 之间的关联已被揭示,但需要更大规模、更多样化的研究来评估其潜在的临床用途。我们扩展了 CRC 患者 (n'Äâ='Äâ930)、腺瘤 (n'Äâ='Äâ210) 和健康对照个体 (n'Äâ='Äâ976;总计 n'Ä='Äâ2,116) 的 12 个宏基因组数据集,其中包含 6 个新队列 (n'Äâ='Äâ1,625) 提供有关癌症分期和肿瘤解剖位置的精细信息。我们仅基于肠道宏基因组学 (曲线下的平均面积'Äâ='Äâ0.85) 提高了 CRC 预测的准确性,并强调了 19 个新分析的物种和不同的梭杆菌核分支的贡献。特定的肠道物种通过丰富的口腔典型微生物来区分左侧和右侧 CRC (曲线下面积'Äâ='Äâ0.66)。我们用共生瘤胃球菌 bicirculans 和 Faecalibacterium prausnitzii 鉴定了菌株特异性 CRC 特征,显示与晚期 CRC 相关的亚分支。我们的分析证实,微生物组可以成为 CRC 筛查的临床靶点,并将其表征为 CRC 进展的生物标志物。