Title:
Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle
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Large-scale metagenomic assembly uncovered thousands of new human microbiome species
•The new genome resource increases the mappability of gut metagenomes over 87%
•Some of the newly discovered species comprise thousands of reconstructed genomes
•Non-Westernized populations harbor a large fraction of the newly discovered species
The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many associated with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the average mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-associated microbes, and allow better exploitation of metagenomic technologies.
Introduction
Despite extensive recent studies of the human microbiome using a variety of culture-independent molecular technologies (Human Microbiome Project Consortium, 2012, Qin et al., 2010, Quince et al., 2017a, Rinke et al., 2013), most characterization of these ecosystems is still focused on microbes that are easily cultivable, particularly when those with sequenced isolate genomes are considered. Since physiological characterization of diverse, uncharacterized human-associated microbes by cultivation can be difficult in high throughput (Browne et al., 2016), additional approaches are needed that scale with the extent of populations that can now be surveyed using metagenomic sequencing. Culture-independent genomic approaches that are scalable to large cohorts (Human Microbiome Project Consortium, 2012, Qin et al., 2010, Quince et al., 2017a) have facilitated access to an expanded set of isolation-recalcitrant members of the microbiome, but they also suggested the presence of a large fraction of still unexplored diversity (Nielsen et al., 2014, Rinke et al., 2013).
Here, we present a set of 154,723 microbial genomes that are often prevalent, population specific, and/or geographically specific that we reconstructed via single-sample assembly from a total of 9,428 global, body-wide metagenomes. Other studies have also succeeded in reconstructing microbial genomes by metagenomic assembly on single human cohorts (Bäckhed et al., 2015, Brooks et al., 2017, Ferretti et al., 2018, Human Microbiome Project Consortium, 2012, Raveh-Sadka et al., 2015, Sharon et al., 2013), but systematic cross-study cataloging of metagenomically assembled genomes focused so far on non-human environments (Oyama et al., 2017, Parks et al., 2017). Complementary techniques, such as co-abundance of gene groups (Nielsen et al., 2014), can identify genomic bins without reference, but these techniques do not account for sample-specific strains and strain-level differences in the sequence reconstruction and thus require downstream single-nucleotide variation analysis on specific genomic regions to uncover strain variability (Quince et al., 2017b, Truong et al., 2017).
Using large-scale single-sample metagenomic assembly supported by strict quality control (including filtering based on nucleotide polymorphisms), we identified 3,796 species-level clades (comprising 34,205 genomes) without previous whole-genome information. This identified several taxa prevalent but previously unobserved even in well-profiled populations (e.g., a genus-level Ruminococcaceaeclade phylogenetically close to Faecalibacterium), extensive taxonomically uncharacterized species associated with non-Western populations, and the presence of several taxa from undersampled phyla (e.g., Saccharibacteria and Elusimicrobia) in oral and gut microbiomes. The resulting genome set can thus serve as the basis for future strain-specific comparative genomics to associate variants in the human microbiome with environmental exposures and health outcomes across the globe.
The rest of the article at the source: https://www.scienced...092867419300017
Edited by Engadin, 25 April 2019 - 10:27 AM.
