Addressing controversy in Fusobacterium nomenclature: what exactly does " F. nucleatum" refer to?

Abstract

The F. nucleatum group (sensu lato) is historically composed of four subspecies (F. nucleatum subsp. animalis, F. nucleatum subsp. nucleatum, F. nucleatum subsp. polymorphum, F. nucleatum subsp. vincentii). Although F. nucleatum sensu lato members are typically associated with oral disease, they have recently been shown to disseminate to the gastrointestinal tract and are associated with adverse health conditions such as inflammatory bowel disease and colorectal cancer (CRC). A growing debate over the nomenclature applied to Fusobacterium taxonomy has resulted in different names for these lineages, shifting them from their historic subspecies designations to distinct species names (F. animalis, F. nucleatum, F. polymorphum, F. vincentii). This shift in naming scheme can lead to potentially significant confusion as "F. nucleatum" can now refer to both the group (sensu lato) and a distinct lineage (sensu stricto; historically F. nucleatum subsp. nucleatum). For example, the substantial body of literature documenting the involvement of "F. nucleatum" (sensu lato) in CRC is seemingly contradicted by recent analyses showing that "F. nucleatum" (sensu stricto) is not enriched in CRC. However, this apparent contradiction is due only to changes in the updated Fusobacterium naming scheme. Furthermore, discrepancies arising from this nomenclature shift can obscure the crucial role of other lineages in tumor biology, particularly that of F. nucleatum subsp. animalis/F. animalis. Thus, the adoption of this nomenclature reclassification without careful consideration risks misleading non-experts and sparking misinterpretation of scientific literature and discourse. Here we elaborate on the challenges of the updated Fusobacterium nomenclature scheme, propose tentative suggestions to improve accuracy and clarity, and call for a broader research community effort to discuss and implement a unified approach moving forward.

Keywords: CRC; Fusobacterium; microbiome profiling; nomenclature; taxonomy.

Figure 1.

Fusobacterium lineage analysis via phylogeny and average nucleotide identity. (Top) A kSNP whole-genome parsimony phylogenetic tree of Fusobacterium genomes (n=224) within the nine GTDB lineages phylogenetically close to the F. nucleatum sensu lato subspecies. Each lineage is highlighted by a different background color. For each, the historic nomenclature and our proposed name with accompanying three-letter abbreviation are shown. (Bottom) a heatmap of average nucleotide identity (ANI) values as calculated by fastANI.

Figure 2.

Guidelines to establish unique code identifiers for Fusobacterium lineages. Flow-chart schematic to establish a unique three- or four-letter code for a Fusobacterium lineage dependent on nomenclature denoted in the genome taxonomy database (GTDB).