Microbial strain-level population structure and genetic diversity from metagenomes

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

707 citations recorded by the source corpus.

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.

Subfields: Food Science, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cb3f96bc631e233015aaf52e465d9b3a61738e74

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Citations in the corpus

Mother-to-Infant Microbial Transmission from Different Body Sites Shapes the Developing Infant Gut Microbiome (2018, methodology): “This rate is even lower than we previously observed for strain sharing among an adult worldwide population (Truong et al., 2017), which was based solely on SNV-based profiling, indicating that the combined approach of gene content and SNV strain profiling used here is more conservative.”
Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4 (2023, background): “StrainPhlAn 4 also allows the analysis of strain sharing and transmission between communities 4,25,28,73,77–79 for uncharacterized species, that is, uSGBs (see Methods).”
The Human Gut Microbiome: From Association to Modulation. (2018, background): “When extending the taxonomic resolution to subspecies level or to a loose operational definition of strains, much more defined geographical patterns become obvious (Costea et al., 2017a; Truong et al., 2017), implying the existence of regional strain pools that harbor different functionality.”
A review of methods and databases for metagenomic classification and assembly (2019, background): “Insights into the functional potential of a microbiome can be gained by matching the reads against pathway or gene databases [53, 54].”
The Pangenome: Diversity, Dynamics and Evolution of Genomes (2020, background): “…accumulation of metagenomic data combined with the development of bioinformatics tools that resolve strain genotypes within metagenomic samples (Nayfach et al. 2016; Pasolli et al. 2017; Truong et al. 2017) constitutes a new source of data readily exploitable to define species based on gene flow.”
A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients (2017, methodology): “While strain-level profiling using StrainPhlAn was carried out for 72 species of the gut microbiome with sufficient coverage, R. gnavus was the only species detected to have an IBD-specific strain.”