PreprintCited by 839Gut microbiota and healthGenomics and Phylogenetic StudiesMicrobial Community Ecology and Physiology

Microbial strain-level population structure and genetic diversity from metagenomes

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Truong, Duy Tin, Tett, Adrian, Pasolli, Edoardo, Huttenhower, Curtis, Segata, Nicola·2017·Genome Research

Abstract

Among the human health conditions linked to microbial communities, phenotypes are often associated with only a subset of strains within causal microbial groups. Although it has been critical for decades in microbial physiology to characterize individual strains, this has been challenging when using culture-independent high-throughput metagenomics. We introduce StrainPhlAn, a novel metagenomic strain identification approach, and apply it to characterize the genetic structure of thousands of strains from more than 125 species in more than 1500 gut metagenomes drawn from populations spanning North and South American, European, Asian, and African countries. The method relies on per-sample dominant sequence variant reconstruction within species-specific marker genes. It identified primarily subject-specific strain variants (<5% inter-subject strain sharing), and we determined that a single strain typically dominated each species and was retained over time (for >70% of species). Microbial population structure was correlated in several distinct ways with the geographic structure of the host population. In some cases, discrete subspecies (e.g., for Eubacterium rectale and Prevotella copri ) or continuous microbial genetic variations (e.g., for Faecalibacterium prausnitzii ) were associated with geographically distinct human populations, whereas few strains occurred in multiple unrelated cohorts. We further estimated the genetic variability of gut microbes, with Bacteroides species appearing remarkably consistent (0.45% median number of nucleotide variants between strains), whereas P. copri was among the most plastic gut colonizers. We thus characterize here the population genetics of previously inaccessible intestinal microbes, providing a comprehensive strain-level genetic overview of the gut microbial diversity.

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  • A large fraction of the gut microbiome's individual uniqueness is encoded at the level of single strains.

    “and a large fraction of this uniqueness is encoded at the level of single strains36–38.”
  • Strain-level characterization of taxa directly from metagenomes is an effective cultivation-free means to profile population structure across geography or other conditions and to track strain transmission.

    “Strain-level characterization of taxa directly from metagenomes is an effective cultivation-free means to profile the population structure of a microbial species across geography or other conditions (Scholz et al., 2016; Truong et al., 2017) and to track strain transmission (Ferretti et al., 2018).”
  • StrainPhlAn performs genotyping at the strain level by reconstructing sample-specific consensus sequences of MetaPhlAn markers and using them for multiple-sequence alignment and phylogenetic modeling.

    “StrainPhlAn performs genotyping at the strain level by reconstructing sample-specific consensus sequences of MetaPhlAn markers and using them for multiple-sequence alignment and phylogenetic modeling (Truong et al., 2017).”

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  1. Ott M, Zola J, Stamatakis A, Aluru S. 2007 Large-scale maximum likelihood-based phylogenetic analysis on the IBM BlueGene/L. In Proceedings of the 2007 ACM/IEEE conference on supercomputing, p. 4 ACM, Reno, NV.

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Authors
Truong, D. T., Tett, A., Pasolli, E., Huttenhower, C., & Segata, N.
Affiliations
  • University of Trento (IT)
  • Broad Institute (US)
Corresponding author
Segata, Nicola
Venue
Genome Research
Published
2017-02-06
Volume
27
Issue
4
Pages
626-638
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
OpenAlex
W2586360538
Cited by
839
References
73
Citations by year
2026: 81 · 2025: 105 · 2024: 112 · 2023: 73 · 2022: 87 · 2021: 158 · 2020: 87 · 2019: 65 · 2018: 46 · 2017: 23 · 2015: 1 · 2014: 1
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Iris (University of Trento) (submittedVersion, cc-by)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health (R01HG005969, U54DE023798)
  • National Science Foundation (DBI-1053486)
  • Army Research Office (W911NF-11-1-0473)
  • Fondazione Caritro (Rif. Int.2014.0325, Rif. Int.2013.0239)
  • EuropeanUnion H2020Marie Skłodowska-Curie Actions ((707345)
  • European Union FP7 Marie-Curie (PCIG13-618833)
  • Ministero dell'Istruzione, dell'Università e della Ricerca (FIR RBFR13EWWI)
  • LEO Pharma Research Foundation
  • Terme di Comano
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
gut microbiota, microbial population structure, human population genetics, Eubacterium rectale, Prevotella copri, Faecalibacterium prausnitzii, Bacteroides
MeSH terms
Algorithms, Bacteroides, Eubacterium, Humans, Polymorphism, Genetic, Genome, Human, Sequence Analysis, DNA, Prevotella, Metagenome, Molecular Typing, Microbiota

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