Page 20 - Read Online

Page 14 of 18 Mueller et al. Microbiome Res Rep 2024;3:33 https://dx.doi.org/10.20517/mrr.2024.09

Table 1. Proposed nomenclature for Akkermansia phylogroups
Previous Proposed nomenclature Type strain Type strain availability Average genome size
nomenclature (Mbp)
T
A. muciniphila AmIa A. muciniphila subspecies Muc ATCC BAA-835 = DSM 2.743
muciniphila 22959
T
A. muciniphila AmIb A. muciniphila subspecies Akk1570 2.816
communis
A. muciniphila AmII A. massiliensis Marseille- CSUR P6666 = CECT 30548 3.112
T
P6666
A. muciniphila AmIII 2.956
T
A. muciniphila AmIV A. biwaensis WON2089 NBRC 115679 = DSM 114407 3.213
A. muciniphila AmV A. ignis MmAkk2 T Submitted to ATCC and DSMZ 2.809
T
A. muciniphila AmVI A. durhamii RCC_12PD Submitted to ATCC and DSMZ 3.161
Our analysis of Akkermansia genomes suggests that the seven major phylogroups, all previsouly classified as A. muciniphila, represent six species
in total. The nomenclature proposed in this and past publications, availability of proposed species type strains, and average proposed species
genome size are listed for each of the seven major clades.

referring to inflammation). The type strain MmAkk2 was isolated from mouse stool. Similarly, since both
T
AmVI isolates were derived from patients in Durham NC, we propose to rename this phylogroup as
Akkermansia durhamii (dur.ham’i.i, N.L. m. n. durhamii, referring to the city of Durham where these
strains were isolated). The type strain is RCC_12PD and was isolated from the stool of a patient with RCC.
T
Both genomic and FAME analysis of multiple isolates indicate that A. ignis is more closely related to
A. muciniphila, and A. durhamii is more related to A. biwaensis. Though reclassifying the AmIII group as a
new species is appropriate based on the described genomic analysis, our laboratory does not have access to
either of the only two isolates described thus far (GP22 and GP24). Because there is currently no type strain
available for public use and our laboratory has not isolated an AmIII strain of our own, we were unable to
perform further phenotypic characterization of this group. Thus, we have chosen not to suggest a new
species epithet or type strain.

We noted marked differences in the genome sizes of the genus Akkermansia, with A. massiliensis,
A. biwaensis, and A. durhamii displaying genomes > 15% larger than A. muciniphila. Based on our
phylogenetic analysis, it appears that the A. biwaensis/A. durhamii split from the A. massiliensis/
A. muciniphila branches, and that these branches evolved separately, with the smaller A. muciniphila
becoming most prominent in human samples worldwide [Figure 1A]. The relative abundance of
A. muciniphila strains is also higher in human stool samples than other Akkermansia species, although their
growth rates, as assessed by SMEG, are relatively equivalent [Figure 3A]. This suggests that factors unrelated
to replication rates (e.g., phage predation, susceptibility to host and microbiota antimicrobial compounds)
may be a more prominent driver of overall Akkermansia abundance in the GI tract.

While different methodologies have been applied for the pangenomic analysis of the Akkermansia genus to
define relationships between Akkermansia and health, these have not generally taken into consideration
subspecies and strain assignments [22,25,27,66,77] . This could be particularly relevant when considering the
potential of Akkermansia strains to be developed into next-generation probiotics [13-16] . The new species
outlined, both as previously suggested [20,22,23,60] and reinforced by the results presented in this study, highlight
that there are clear phenotypic differences that may be relevant to the interaction between Akkermansia and
the host. Indeed, we find species and subspecies level assignments refine the outcome of associations
between Akkermansia and humans, where one sub-species may drive the associations observed in the past,
as in the case of increased responsiveness to PD-1 blockade in patients colonized by AmIa Akkermansia.
Thus, targeting specific strains to be developed into future probiotics should include an analysis of which