Through large-scale culturing, sequencing and comparative genomic analyses of human CRC and non-cancer oral Fn strains, we revealed the distinct CRC-enriched genetic factors of Fn. Further, we identified that these CRC-enriched factors were predominantly present within a specific clade of Fna. This was mirrored by our discovery that Fna is bifurcated into two distinct clades: Fna C1, which is largely restricted to the oral cavity, and Fna C2, which dominates the human CRC tumour niche. This evidence concerns the gene FN1 and neoplasm.