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Page 6 of 8 Kumar et al. Microbiome Res Rep 2024;3:37 https://dx.doi.org/10.20517/mrr.2024.28

Figure 2. Functional characterization of propionate synthesis pathway of Akkermansia species using representative isolates:
Akkermansia massiliensis sp. nov strain DSM 33459, A. massiliensis strain Marseille-P6666T (CECT 30548), and Akkermansia muciniphila
strain BAA-835T (ATCC BAA-835).

Karcher et al. showed that the absence of the corrin ring biosynthesis operon genes in A. muciniphila
resulted in an inability to produce propionate in the absence of vitamin B . As depicted in Figure 2, we
[9]
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similarly measured the Vitamin B -dependent production of propionate in strains Akkermansia massiliensis
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sp. nov. DSM33459, Type Akkermansia massiliensis CECT 30548 and Type Akkermansia muciniphila ATCC
BAA-835. Cells were grown in the defined media as published by Karcher et al. . Supernatants were
[9]
collected at 48 h of growth and propionate was measured using HPLC. Strains A. massiliensis sp. nov.
DSM33459 and Type A. massiliensis sp. nov. CECT 30548 showed similar production of propionate
irrespective of the addition of B in the media. Type A. muciniphila ATCC BAA-835 strain showed
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propionate production only in the presence of externally added B , suggesting its dependency on the
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external B for propionate production as shown by Kirmiz et al. and Karcher et al. [9,26] . Propionate
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production is dependent on the B -dependent methyl-malonyl CoA synthase reaction . The presence of
[27]
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the corrin ring biosynthesis operon and, hence, the ability to synthesize vitamin B in A. massiliensis sp.
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nov. broadens its potential for human health. Recently, it has been shown that gut resident vitamin B -
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producing bacteria can modulate excitatory cholinergic signaling and behavior in the host
Caenorhabditis elegans . Additionally, it is currently unknown, but possible that Akkermansia sp. may play
[28]
a role in shaping the microbiome in the human gastrointestinal tract by providing the enzyme co-factor
vitamin B to other bacterial species.
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While these newly proposed mechanisms require further investigation and confirmation in in vivo studies,
they do support further investigation of A. massiliensis sp. nov. in first-in-human intervention studies to
study possible health benefits. The human gut commensal A. muciniphila remains the most studied
beneficial bacterial species within the genus Akkermansia; however, the emergence of new species such as
A. massiliensis sp. nov. presents new opportunities for the development of effective and targeted
Akkermansia species-based interventions to provide health benefits.

DECLARATIONS
Authors’ contributions
Conception, content, and interpretation of the article: Kumar R, Hasselwander O, Kane H, Hibberd AA