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Kumar et al. Microbiome Res Rep 2024;3:37 https://dx.doi.org/10.20517/mrr.2024.28 Page 3 of 8

[6]
Figure 1. Genomic phylogenetic tree and corresponding proteome . Type strains of validly published species are denoted in red.
35 kg/m ) women residing in Finland. Similar to Karcher et al. , we found A. muciniphila to be both more
[9]
2
prevalent and abundant in all of the cohorts compared to A. massiliensis sp. nov. [Table 1]. The prevalence
of A. massiliensis sp. nov. was higher in the American Gut Project, IsoMic, and NGPs for MH lean cohorts
(14.7%, 11.5%, and 26.3%, respectively), compared to the average abundance (8%) reported by Karcher
et al. . The exception was the NGPs for MH obese cohort, where, intriguingly, the colonization of
[9]
A. massiliensis sp. nov. was not detected in any of the individuals. Interestingly, only a small percentage of
individuals were co-colonized with both A. municiphila and A. massiliensis sp. nov., suggesting that these
[9]
two species may be mutually exclusive. This agrees with Karcher et al. , who also showed a strong negative
correlation between their co-occurrence in 4,171 human metagenomes. A. biwaensis was undoubtedly the
most rarely detected human-associated Akkermansia species, but we found its prevalence was 8.9% in the
American Gut Project cohort, with an average abundance of 0.2%. This prevalence is perhaps higher than
expected for this almost completely unexplored species in human microbiomes. These findings support the
exploration of potential metabolic health benefits associated with the colonization of A. massiliensis sp. nov.
and warrant future mechanistic studies to better understand the interplay among A. muciniphila and the
less abundant Akkermansia species and their impact on the host.

Two studies have looked in more detail at associations between colonization with different Akkermansia
species and respective health outcomes. Karcher et al. reported that in a sample set of 3,311 genomes
coming from different metagenomic datasets and isolates, only A. muciniphila was significantly negatively
[9]
associated with BMI . In addition, a more recent analysis by Mueller et al., who re-analyzed metagenomic
datasets of patients with obesity, inflammatory bowel disease, and response to cancer immunotherapy,
reported that there were no significant correlations between abundances of A. muciniphila and
A. massiliensis and obesity in children . Only A. muciniphila was, however, found to be significantly
[12]
reduced in samples from patients with ulcerative colitis compared to healthy controls. In addition, patients
with non-small-cell lung cancer undergoing immune checkpoint inhibitor treatment colonized with
A. muciniphila clade AmIa had an increase in survival compared to patients with no detectable
A. muciniphila. Mueller et al. reported the prevalence of the different Akkermansia species similar to those
in Table 1, with A. muciniphila being the most prevalent species [32.5% of 1,088 samples, followed by
A. massiliensis (11.9%) and A. biwaensis (5.2%)] . This lower prevalence of Akkermansia species other than
[12]
A. muciniphila means that much larger datasets are required to thoroughly investigate correlations between
human health outcomes and the relative abundance of these Akkermansia species.