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Cell. 2019 Jan 24;176(3):649-662.e20. doi: 10.1016/j.cell.2019.01.001. Epub 2019 Jan 17.

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

Author information

1
CIBIO Department, University of Trento, Trento, Italy.
2
Institute of Agrochemistry and Food Technology-National Research Council, Valencia, Spain.
3
Harvard University, Cambridge, MA, USA.
4
Harvard T.H. Chan School of Public Health, Boston, MA, USA.
5
University of Otago, Otago, New Zealand.
6
Warwick Medical School, University of Warwick, Warwick, UK.
7
Harvard T.H. Chan School of Public Health, Boston, MA, USA; The Broad Institute, Cambridge, MA, USA.
8
CIBIO Department, University of Trento, Trento, Italy. Electronic address: nicola.segata@unitn.it.

Abstract

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.

KEYWORDS:

human microbiome; metagenomic assembly; metagenomic mappability; metagenomic meta-analysis; metagenomics; non-Westernized microbiomes; unexplored microbial diversity

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