Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle

Summary

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.

Graphical Abstract

Highlights

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  Large-scale metagenomic assembly uncovered thousands of new human microbiome species

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  The new genome resource increases the mappability of gut metagenomes over 87%

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  Some of the newly discovered species comprise thousands of reconstructed genomes

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  Non-Westernized populations harbor a large fraction of the newly discovered species

Abstract

The human microbiome harbors many unidentified species. By large-scale metagenomic assembly of samples from diverse populations, we uncovered >150,000 microbial genomes that are recapitulated in 4,930 species. Many species (77%) were never described before, increase the mappability of metagenomes, and expand our understanding of global body-wide human microbiomes.