Akkermansia muciniphila is a mucin-degrading bacterium found in the gut of most humans and is considered a "next-generation probiotic." However, knowledge of the genomic and physiological diversity of human-associated Akkermansia sp. strains is limited. Here, we reconstructed 35 metagenome-assembled genomes and combined them with 40 publicly available genomes for comparative genomic analysis. We identified at least four species-level phylogroups (AmI to AmIV), with distinct functional potentials. Most notably, we identified genes for cobalamin (vitamin B₁₂) biosynthesis within the AmII and AmIII phylogroups. To verify these predictions, 10 Akkermansia strains were isolated from adults and screened for vitamin B₁₂ biosynthesis genes via PCR. Two AmII strains were positive for the presence of cobalamin biosynthesis genes, while all 9 AmI strains tested were negative. To demonstrate vitamin B₁₂ biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups, since cobalamin is an essential cofactor in propionate metabolism. Results showed that the AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of vitamin B₁₂ biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B₁₂ was not supplied in the culture medium. Lastly, two bioassays were used to confirm vitamin B₁₂ production by the AmII phylogroup. This novel physiological trait of human-associated Akkermansia strains may affect how these bacteria interact with the human host and other members of the human gut microbiome.

IMPORTANCE There is significant interest in the therapeutic and probiotic potential of the common gut bacterium Akkermansia muciniphila. However, knowledge of both the genomic and physiological diversity of this bacterial lineage is limited. Using a combination of genomic, molecular biological, and traditional microbiological approaches, we identified at least four species-level phylogroups with differing functional potentials that affect how these bacteria interact with both their human host and other members of the human gut microbiome. Specifically, we identified and isolated Akkermansia strains that were able to synthesize vitamin B₁₂. The ability to synthesize this important cofactor broadens the physiological capabilities of human-associated Akkermansia strains, fundamentally altering our understanding of how this important bacterial lineage may affect human health.

Akkermansia muciniphila是一种在大多数人的肠道中发现的降解粘蛋白的细菌，被认为是“下一代益生菌”。但是，人类相关的Akkermansia sp。的基因组和生理多样性的知识。应变是有限的。在这里，我们重建了35个由元基因组组装的基因组，并将它们与40个可公开获得的基因组结合起来，用于比较基因组分析。我们确定了至少四个物种水平的phylogroups（AmI到AmIV），具有不同的功能潜力。最值得注意的是，我们确定了AmII和AmIII系统族内钴胺素（维生素B ₁₂）生物合成的基因。为了验证这些预测，从成年人中分离出10种Akkermansia菌株，并筛选了维生素B ₁₂PCR合成生物合成基因。两株AmII菌株对钴胺素生物合成基因的检测呈阳性，而所有9株检测的AmI菌株均为阴性。为了证明维生素B _12的生物合成，我们测量了在AmI和AmII phylogroups代表菌株中补充和不补充维生素的情况下乙酸盐，琥珀酸盐和丙酸的产生，因为钴胺素是丙酸代谢中必不可少的辅助因子。结果表明，AmII菌株在不补充的情况下产生乙酸盐和丙酸盐，这表明维生素B _12的生物合成。相反，当维生素B ₁₂时，乙酸盐和琥珀酸盐是AmI菌株的主要发酵产物。未在培养基中提供。最后，使用两个生物测定法来确认AmII系统群产生的维生素B ₁₂。与人类有关的阿克曼菌属菌株的这种新的生理特性可能会影响这些细菌与人类宿主和人类肠道微生物组其他成员的相互作用方式。

重要事项常见的肠道细菌黏液阿克曼（Akkermansia muciniphila）具有治疗和益生作用的潜力。但是，这种细菌谱系的基因组和生理多样性的知识是有限的。使用基因组学，分子生物学和传统微生物学方法的组合，我们确定了至少四个具有不同功能潜能的物种级系统群，这些潜能影响这些细菌与人类宿主和人类肠道微生物组其他成员的相互作用方式。具体来说，我们鉴定并分离出能够合成维生素B _12的阿克曼菌菌株。合成这种重要辅因子的能力拓宽了人类相关的阿克曼氏菌菌株的生理能力，从根本上改变了我们对这种重要细菌谱系如何影响人类健康的理解。