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Figure 4. The association between Akkermansia and improved survival following PD-1 blockade treatment depends on the dominant
Akkermansia species and sub-phylogroup. (A) A Cox regression model was used to determine the factors associated with prolonged
survival after treatment for non-small-cell lung cancer. Cumulative survival is displayed using dominant Akkermansia species as the
predictive variable, colored by species. The line for A. massiliensis is dotted to make the line for Akkermansia-negative samples visible; (B)
The tabular results of the Cox regression model reveal that the relationship between Akkermansia and prolonged survival is specific to
A. muciniphila (AmI); (C) A Cox regression model was used to determine the factors associated with prolonged survival after treatment
for non-small-cell lung cancer. Cumulative survival is displayed using the dominant A. muciniphila phylogroup as the predictive variable;
(D) The tabular results of the Cox regression model reveal that the relationship between A. muciniphila and prolonged survival is specific
to the AmIa phylogroup.

determinant of species classification is limited [75,76] . These studies suggest that whole genome data
methodologies, such as producing single-copy core gene phylogenies and ANI clustering, are more
appropriate for demarcating closely related species. Indeed, the AmII and AmIV phylogroups were recently
renamed A. massiliensis and A. biwaensis, respectively [23,29,30] . The report that renamed Akkermansia AmII as
A. massiliensis suggested that the AmIV phylogroup also met the criteria of a new species and proposed the
name “Candidatus Akkermansia timonensis”. However, several AmIV strains had been previously isolated
and their genomes sequenced, making the Candidatus term inappropriate [20,60] . Overall, the results of our
study indicate that A. muciniphila should be split into several species including A. muciniphila,
A. massiliensis, and A. biwaensis. The AmV, AmIII, and AmVI groups should be defined as novel species as
well [Table 1]. We propose that the AmIa phylogroup of A. muciniphila be renamed as A. muciniphila
subsp. muciniphila, given that the type strain of A. muciniphila, Muc , belongs to this subspecies. We
T
propose that the AmIb phylogroup be renamed as A. muciniphila subsp. communis (kom’mu.nis. L. m. adj.
communis common, referring to this subspecies being more prevalent than subsp. muciniphila among
T
MAGs and isolates). The type strain subsp. communis Akk1570 was isolated from the stool of a child with
obesity. Given that two AmV isolates were from mice with different chronic intestinal inflammatory
disorders , we propose that this phylogroup be renamed Akkermansia ignis (ig.nis. L. m. n. ignis fire,
[21]