Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas.

Background: Akkermansia muciniphila is one of the most dominant bacteria that resides on the mucus layer of intestinal tract and plays key role in human health, however, little is known about its genomic content.

Results: Herein, we for the first time characterized the genomic architecture of A. muciniphila based on whole-genome sequencing, assembling, and annotating of 39 isolates derived from human and mouse feces. We revealed a flexible open pangenome of A. muciniphila currently consisting of 5644 unique proteins. Phylogenetic analysis identified three species-level A. muciniphila phylogroups exhibiting distinct metabolic and functional features. Based on the comprehensive genome catalogue, we reconstructed 106 newly A. muciniphila metagenome assembled genomes (MAGs) from available metagenomic datasets of human, mouse and pig gut microbiomes, revealing a transcontinental distribution of A. muciniphila phylogroups across mammalian gut microbiotas. Accurate quantitative analysis of A. muciniphila phylogroups in human subjects further demonstrated its strong correlation with body mass index and anti-diabetic drug usage. Furthermore, we found that, during their mammalian gut evolution history, A. muciniphila acquired extra genes, especially antibiotic resistance genes, from symbiotic microbes via recent lateral gene transfer.

Conclusions: The genome repertoire of A. muciniphila provided insights into population structure, evolutionary and functional specificity of this significant bacterium.