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).