Profiling Fusobacterium infection at high taxonomic resolution reveals lineage-specific correlations in colorectal cancer

The bacterial genus Fusobacterium promotes colorectal cancer (CRC) development, but an understanding of its precise composition at the species level in the human gut and the relevant association with CRC is lacking. Herein, we devise a Fusobacterium rpoB amplicon sequencing (FrpoB-seq) method that enables the differentiation of Fusobacterium species and certain subspecies in the microbiota. By applying this method to clinical tissue and faecal samples from CRC patients, we detect 62 Fusobacterium species, including 45 that were previously undescribed. We additionally reveal that Fusobacterium species may display different lineage-dependent functions in CRC. Specifically, a lineage (designated L1) including F. nucleatum , F. hwasookii , F. periodonticum and their relatives (rather than any particular species alone) is overabundant in tumour samples and faeces from CRC patients, whereas a non-enriched lineage (designated L5) represented by F. varium and F. ulcerans in tumours has a positive association with lymphovascular invasion.