A distinct Fusobacterium nucleatum clade, Fna C2, that is dominant in the human colorectal cancer (CRC) niche has been identified in a new study published in Nature. Importantly, in mice, Fna C2 treatment led to increased numbers of large intestinal adenomas and altered metabolite profiles. The findings illuminate the crucial connection between a bacterial subspecies and human colon cancer and provide further insights into the cancer microbiome.

The investigators generated closed genomes from 135 F. nucleatum strains (80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC), identifying 483 CRC-enriched genetic factors (versus 241 gene clusters highly prevalent in oral strains). Moreover, tumour-isolated strains predominantly belonged to F. nucleatum subsp. animalis, but further pangenome analysis revealed that this subspecies was actually composed of two distinct clades (Fna C1 and Fna C2). Crucially, the Fna C2 clade was enriched in the CRC niche, whereas the Fna C1 clade was largely restricted to the oral cavity, and had distinct differences from the C1 clade, including the presence of additional virulence factors (including fap2, cmpA and fusolisin) and distinct morphologies (Fna C2 cells were longer and thinner).

《自然》杂志发表的一项新研究发现了一种独特的具核梭杆菌分支Fna C2，它在人类结直肠癌 (CRC) 生态位中占主导地位。重要的是，在小鼠中，Fna C2 治疗导致大肠腺瘤数量增加并改变代谢谱。这些发现阐明了细菌亚种与人类结肠癌之间的重要联系，并为癌症微生物组提供了进一步的见解。

研究人员从 135 个 具核梭杆菌菌株（80 个来自非癌症个体的口腔菌株和从 51 名 CRC 患者的肿瘤中培养的 55 个独特癌症菌株）中生成了封闭基因组，鉴定了 483 个富含 CRC 的遗传因子（相对于口腔中高度流行的 241 个基因簇）。菌株）。此外，肿瘤分离菌株主要属于具核梭杆菌亚种。但进一步的全基因组分析表明，该亚种实际上由两个不同的分支（ Fna C1 和Fna C2）组成。至关重要的是，Fna C2 进化枝在 CRC 生态位中富集，而Fna C1 进化枝主要局限于口腔，并且与 C1 进化枝有明显差异，包括存在额外的毒力因子（包括fap2、cmpA和Fusolisin）和不同的形态（Fna C2 细胞更长更薄）。