A thousand metagenome-assembled genomes of Akkermansia reveal phylogroups and geographical and functional variations in the human gut

Abstract

Akkermansia muciniphila has long been considered to be the only Akkermansia species in the human gut and has been extensively studied. The present study revealed the genomic architecture of Akkermansia in the human gut by analyzing 1,126 near-complete metagenome-assembled genomes, 84 publicly available genomes, and 1 newly sequenced Akkermansia glycaniphila strain from the human gut. We found that 1) the genomes of Akkermansia were clustered into four phylogroups with distinct interspecies similarity and different genomic characteristics and 2) A. glycaniphila GP37, a strain of Akkermansia, was isolated from the human gut, whereas previously, it had only been found in python. Amuc III was present in the Chinese population, and Amuc IV was mainly distributed in Western populations. A large number of gene functions, pathways, and carbohydrate-active enzymes were specifically associated with phylogroups. Our findings based on over a thousand genomes strengthened our previous knowledge and provided new insights into the population structure and ecology of Akkermansia in the human gut.

Insights into early evolutionary adaptations of the Akkermansia genus to the vertebrate gut

“…The clade A comprised A. muciniphila and other related species (GTDB names sp900545155, sp905200945, muciniphila_A, muciniphila_B, muciniphila_E, muciniphila_C, sp001580195, sp004167605, and Cluster25, without no specific species level classification in GTDB). Compared with previous studies ( Karcher et al, 2021 ; Lv et al, 2022 ), the GTDB A. muciniphila genomic species corresponds to the Amuc I phylogroup, whereas Akkermansia muciniphila_B corresponds to Amuc II , Akkermansia muciniphila_C to Amuc III , and Akkermansia sp001580195 to Amuc IV . On the other hand, Clade B includes A. glycaniphila, Ca .…”

“…Recently, comparative genomics and A. muciniphila pangenome studies have been performed multiple times ( van Passel et al, 2011 ; Guo et al, 2017 ; Xing et al, 2019 ; Lv et al, 2020 ; Geerlings et al, 2021 ; Karcher et al, 2021 ; Kim et al, 2022 ; Li et al, 2022 ; Lv et al, 2022 ; Ouwerkerk et al, 2022 ). However, the use of an Orthofinder-based strategy is not common.…”

Dysbiosis and reduced small intestinal function are required to induce intestinal insufficiency in mice

“…Another effect of ICR is the decrease of Verrucomicrobia, which in our study appeared as early as 2 days after removal of the cecum and which in rats remained decreased even 28 days after 75% ICR ( 10 ). To date, Akkermansia muciniphila and, more recently, also Akkermansia glycaniphila have been isolated from the human intestine, the latter being found preferentially in nonmammals ( 34 ). A. muciniphila is widely distributed in the intestines of human and mice where it colonizes the outer mucosal layer, being most abundant in the cecum ( 35 ).…”

Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases

“…The prevalence of Amuc4 was more commonly found in non-Westernized human populations compared to non-Amuc4 species. Analysis of metagenome-assembled genomes of Akkermansia revealed that Amuc III mainly distributed in the Chinese population and Amuc IV was more commonly present in Western populations, whereas Amuc I and II distributed extensively globally ( Lv et al, 2022 ). The representative genomes of Amuc I, II, III, and IV showed diversified genomic characteristics involved in multiple metabolism and transport pathways, which suggests different evolution history and functional habits.…”