New insights from uncultivated genomes of the global human gut microbiome
Open accessAbstract
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. Draft prokaryotic genomes from faecal metagenomes of diverse human populations enrich our understanding of the human gut microbiome by identifying over two thousand new species-level taxa that have numerous disease associations.
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Microbiome members of individuals from non-westernized populations are underrepresented by current cultivation-based genomic catalogs, causing metagenomic profiling to miss large fractions of microbial diversity.
“Microbiome members of individuals from non-westernized populations are particularly underrepresented by current cultivation-based genomic catalogs causing metagenomic profiling approaches to miss large fractions of the microbial diversity in the samples.”
From Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population (2023) · cites this paper as [25]
Metagenomic assembly can partially mitigate the underrepresentation of non-westernized microbiome members in genomic catalogs.
“Recent efforts showed that metagenomic assembly can partially mitigate this problem,23,25,33,34”
From Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population (2023) · cites this paper as [25]
Similar, albeit less marked, patterns of microbiome composition differences by lifestyle were already observed for adults but were never investigated in younger individuals.
“Similar, albeit less marked, patterns were already observed for adults22,23,24,25 with different lifestyles but were never investigated in younger individuals.”
From Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population (2023) · cites this paper as [25]
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- Authors
- Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S., & Kyrpides, N. C.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Gladstone Institutes (US)
- Corresponding author
- Nayfach, Stephen
- Kyrpides, Nikos C.
- Venue
- Nature
- Published
- 2019-03-13
- Volume
- 568
- Issue
- 7753
- Pages
- 505-510
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6784871
- OpenAlex
- W2921815890
- Cited by
- 737
- References
- 87
- Citations by year
- 2026: 59 · 2025: 102 · 2024: 99 · 2023: 92 · 2022: 110 · 2021: 150 · 2020: 90 · 2019: 35
- FWCI
- 34.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation (1563159, DEAC02-05CH11231)
- U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE AC02 05CH11231, DE-AC02-)
- Gladstone Institutes
- Joint Genome Institute (AC02-05CH11231, DE–AC02–05CH11231)
- Office of Science (DEAC02–05CH11231, AC02-05CH11231, DE-AC02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Keywords
- human gut microbiome, uncultured bacteria, microbial diversity, rural population, disease association, genome reduction, cultivation strategies
- MeSH terms
- Gastrointestinal Microbiome, Bacteria, Disease, Feces, Humans, Phylogeny, Rural Population, Species Specificity, Genome, Bacterial, Bacterial Physiological Phenomena, Genomics, Biosynthetic Pathways, Metagenome, Geographic Mapping
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