Abstract
The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, diversity, biogeography, and molecular function. The National Institutes of Health Human Microbiome Project has provided one of the broadest such characterizations so far. Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics.
Highlights
Body-wide strain diversity and ecology The diversity and spatiotemporal distributions of strains were first investigated using StrainPhlAn14 (Fig. 1), which identifies the domi nant haplotype (‘strain’) of each sufficiently abundant species in a metagenome (Methods, Supplementary Table 2)
Culture-independent strain profiling, in combination with the 16,903 NCBI isolate genomes used as references in this analysis19, provided a new quantification20 of how well covered human microbial diversity is by these references (Fig. 1f)
Searching for co-occurrence patterns with non-bacterial species (Fisher’s exact test, presence/absence threshold of 0.1% relative abundance; Supplementary Table 3), we found that Methanobrevibacter smithii tended to co-occur with several Clostridiales species in the gut, including members of Ruminococcus, Coprococcus, Eubacterium, and Dorea (false discovery rate (FDR) less than 0.1), reinforcing previous observations21 and consistent with co-occurrence patterns of methanogens and clostridia in lean versus obese individuals22
Summary
We provide and analyse the largest known body-wide metageno mic profile of the human microbiome to date. Species with human microbiome strain diversity under-represented in isolate genomes were identified, to be prioritized for isolation and sequencing. Gaussian process models characterized microbial and functional variation over time, and identified the composition of the gut community (Bacteroidetes species in particular) as highly personalized compared to other sites. This example implies that the gut Bacteroidetes/Firmicutes balance may not be a defining attribute of an individual’s gut microbiome; instead, individuals carry a ‘personal equilibrium’ among Bacteroidetes, with a group of phylogenetically diverse, temporally variable Firmicutes fluctuating atop this core. Function and diversity of the healthy human microbiome. 5. Qin, J. et al A human gut microbial gene catalogue established by metagenomic sequencing. Schloissnig, S. et al Genomic variation landscape of the human gut microbiome. Functional and phylogenetic assembly of microbial communities in the human microbiome.
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