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Nature. 2019 Apr;568(7753):505-510. doi: 10.1038/s41586-019-1058-x. Epub 2019 Mar 13.

New insights from uncultivated genomes of the global human gut microbiome.

Nayfach S1,2, Shi ZJ3,4, Seshadri R5,6, Pollard KS3,4,7,8,9,10, Kyrpides NC11,12.

Author information

1
United States Department of Energy Joint Genome Institute, Walnut Creek, CA, USA. snayfach@lbl.gov.
2
Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. snayfach@lbl.gov.
3
Gladstone Institutes, San Francisco, CA, USA.
4
Chan-Zuckerberg Biohub, San Francisco, CA, USA.
5
United States Department of Energy Joint Genome Institute, Walnut Creek, CA, USA.
6
Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
7
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
8
Institute for Computational Health Sciences, University of California San Francisco, San Francisco, CA, USA.
9
Quantitative Biology Institute, University of California San Francisco, San Francisco, CA, USA.
10
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
11
United States Department of Energy Joint Genome Institute, Walnut Creek, CA, USA. nckyrpides@lbl.gov.
12
Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. nckyrpides@lbl.gov.

Abstract

The genome sequences of many species of the human gut microbiome remain unknown, largely owing to challenges in cultivating microorganisms under laboratory conditions. Here we address this problem by reconstructing 60,664 draft prokaryotic genomes from 3,810 faecal metagenomes, from geographically and phenotypically diverse humans. These genomes provide reference points for 2,058 newly identified species-level operational taxonomic unitsĀ (OTUs), which represents a 50% increase over the previously known phylogenetic diversity of sequenced gut bacteria. On average, the newly identified OTUs comprise 33% of richness and 28% of species abundance per individual, and are enriched in humans from rural populations. A meta-analysis of clinical gut-microbiome studies pinpointed numerous disease associations for the newly identified OTUs, which have the potential to improve predictive models. Finally, our analysis revealed that uncultured gut species have undergone genome reduction that has resulted in the loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.

PMID:
30867587
DOI:
10.1038/s41586-019-1058-x

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