Abstract
BackgroundAkkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored.ResultsWe present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila, the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila, that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon.ConclusionsWe uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.
Highlights
The human body is home to several distinct microbiomes which represent functionally and phylogenetically diverse microbial ecosystems that are key for human health [1,2,3]
A large-scale metagenomics-based analysis of Akkermansia candidate species In order to study the diversity of Akkermansia species in the human microbiome, we collected all genomes available from isolate sequencing as well as metagenome-assembled genomes (MAGs) from large collections of metagenomic datasets and unified them into a single genomic resource
Our analysis showed that CRISPR spacer sequences found in the genome of Akkermansia candidate species can be frequently mapped to four putative phages that co-occur with their cognate candidate species, suggesting that they are ecologically interacting in the human gut
Summary
The human body is home to several distinct microbiomes which represent functionally and phylogenetically diverse microbial ecosystems that are key for human health [1,2,3]. The genomic variation of conspecific strains often exceeds 3% nucleotide variation in the core genes, and when comparing pairs of conspecific strains, it is frequently observed that 25% of genes are present in only one of the two, causing each human microbiome to be unique at the strain level [3]. This subspecies genomic variability translates into phenotypic variability, for example, in connection with host lifestyle [14,15,16] and at the immunological level [17, 18]. The genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored
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