Karcher Nicolai, Nigro Eleonora, Punčochář Michal, Blanco-Míguez Aitor, Ciciani Matteo, Manghi Paolo, Zolfo Moreno, Cumbo Fabio, Manara Serena, Golzato Davide, Cereseto Anna, Arumugam Manimozhiyan, Bui Thi Phuong Nam, Tytgat Hanne L P, Valles-Colomer Mireia, de Vos Willem M, Segata Nicola
Department CIBIO, University of Trento, Trento, Italy.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Genome Biol. 2021 Jul 14;22(1):209. doi: 10.1186/s13059-021-02427-7.
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.
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.
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.
嗜黏蛋白阿克曼氏菌是一种人类肠道微生物，在肠道黏液层的生理功能中起关键作用，据报道与体重减轻、肠道屏障功能增强及健康状况改善有关。尽管其具有生物医学相关性，但嗜黏蛋白阿克曼氏菌的基因组多样性仍研究不足，除嗜糖阿克曼氏菌外，与其密切相关物种的基因组多样性尚未得到探索。
我们使用188个分离株基因组和从18600个人类及其他动物宏基因组中组装的2226个基因组，对阿克曼氏菌属进行了大规模群体基因组学分析。虽然我们未检测到嗜糖阿克曼氏菌，但人类肠道中的阿克曼氏菌菌株可分为五个不同的候选物种，包括嗜黏蛋白阿克曼氏菌，尽管它们的16S rRNA基因序列惊人地相似，但全基因组却存在显著差异。这些候选物种可能是人类特有的，因为它们几乎只在圈养的小鼠和非人类灵长类动物中被检测到。在人类中，阿克曼氏菌候选物种表现出生态共排斥、功能能力多样化以及与宿主体重的不同关联模式。对CRISPR-Cas位点的分析揭示了针对新发现的假定噬菌体的新变体和间隔序列。值得注意的是，当存在同源预测噬菌体时，我们观察到阿克曼氏菌的相对丰度增加，这表明存在生态相互作用。嗜黏蛋白阿克曼氏菌进一步表现出亚种水平的遗传分层以及相关的功能差异，例如一个假定的外切/脂多糖操纵子。
我们揭示了人类中阿克曼氏菌属的大量系统发育和功能多样性。在正在进行的实验和宏基因组学研究中，为了表征嗜黏蛋白阿克曼氏菌及相关细菌与健康相关的特性，应考虑这种变异性。
