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 units (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.
Highlights
The genome sequences of many species of the human gut microbiome remain unknown, largely owing to challenges in cultivating microorganisms under laboratory conditions
Considerable efforts have been made to culture and sequence members of the gut microbiome[5,6,7], many microorganisms have not been grown under laboratory conditions to date and lack a sequenced genome—despite being prevalent in humans[8]
Microbial communities with high diversity were enriched for newly identified operational taxonomic units (OTUs), no difference was observed between the microbiomes of healthy individuals and individuals with disease (Extended Data Fig. 4f, Supplementary Tables 13, 14). These results reveal that the uncultured OTUs discovered in this study comprise a considerable fraction of the healthy human gut microbiome, and that they are more common in non-Western populations
Summary
Given the overall pattern of genome reduction, we identified functions that were frequently missing from uncultured OTUs using phylogenetic logistic regression and annotations from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (Methods). We found 1,492 KEGG orthology groups (21.5% of total) that significantly differed between groups at a false discovery rate of
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