TY - JOUR

T1 - Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly

AU - Karcher, Nicolai

AU - Nigro, Eleonora

AU - Puncochar, Michal

AU - Blanco-Miguez, Aitor

AU - Ciciani, Matteo

AU - Manghi, Paolo

AU - Zolfo, Moreno

AU - Cumbo, Fabio

AU - Manara, Serena

AU - Golzato, Davide

AU - Cereseto, Anna

AU - Arumugam, Manimozhiyan

AU - Bui, Thi Phuong Nam

AU - Tytgat, Hanne L. P.

AU - Valles-Colomer, Mireia

AU - de Vos, Willem M.

AU - Segata, Nicola

PY - 2021

Y1 - 2021

N2 - Background Akkermansia 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. Results We 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. Conclusions We 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.

AB - Background Akkermansia 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. Results We 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. Conclusions We 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.

KW - CRISPR-CAS SYSTEMS

KW - ANTIBIOTIC-RESISTANCE

KW - GEN. NOV.

KW - MUCINIPHILA

KW - ALIGNMENT

KW - BACTERIUM

KW - DRIVEN

KW - VIROME

KW - TOOL

U2 - 10.1186/s13059-021-02427-7

DO - 10.1186/s13059-021-02427-7

M3 - Journal article

C2 - 34261503

VL - 22

JO - Genome Biology (Online Edition)

JF - Genome Biology (Online Edition)

SN - 1474-7596

M1 - 209

ER -