Journal
GENOME RESEARCH
Volume 27, Issue 4, Pages 626-638Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.216242.116
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Funding
- National Institutes of Health (NIH) [R01HG005969, U54DE023798]
- National Science Foundation (NSF) [DBI-1053486]
- Army Research Office grant [W911NF-11-1-0473]
- Fondazione Caritro grant [Rif. Int.2014.0325, Rif. Int.2013.0239]
- European Union H2020 Marie Sklodowska-Curie Actions grant [707345]
- European Union FP7 Marie-Curie grant [PCIG13-618833]
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) grant [FIR RBFR13EWWI]
- LEO Pharma Research Foundation
- Terme di Comano grants
- Marie Curie Actions (MSCA) [707345] Funding Source: Marie Curie Actions (MSCA)
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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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