Multi-omic comparative analysis of members of the <i>Akkermansia</i> genus reveals species-specific adaptations to growth in mucin

<i>Akkermansia muciniphila</i> is a commensal, mucophilic anaerobic bacterium that influences human host physiology. Although additional prominent <i>Akkermansia</i> species have been identified in humans, their responses to mucin-rich environments remain poorly understood. We conducted a comparative analysis of four representative human isolates: <i>A. muciniphila, A. biwaensis, A. massiliensis,</i> and <i>A. durhamii,</i> focusing on proteins involved in mucin degradation, cell-surface components, and species-specific secreted metabolites during growth in mucin. Our results reveal unique adaptations of <i>A. muciniphila</i> to exploit mucin-rich environments, including higher expression of key mucin-degrading proteins during growth in mucin compared to other <i>Akkermansia</i> species. We also demonstrate that <i>A. muciniphila</i> expresses a significantly greater number of secreted PEPCTERM proteins, which contribute to host colonization. The expression of pili-associated proteins varied across species, with non- <i>muciniphila</i> species producing more predicted pili, suggesting the ability to colonize additional niches. Lastly, we find that small peptides previously linked to host and microbiome modulation in the GI tract are over-represented in the metabolomes of non- <i>muciniphila</i> species. Conversely, <i>A. muciniphila</i> produces more hydroxylated fatty acids, indicating potential mechanisms for modulating host health. These findings highlight genetic and regulatory mechanisms that may explain <i>A. muciniphila</i> 's dominance in the human gut.