Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle

By Edoardo Pasolli, F. Asnicar, S. Manara, Moreno Zolfo, Nicolai Karcher, F. Armanini, F. Beghini, Paolo Manghi, Adrian Tett, P. Ghensi and 8 more. Cell, 2019

1,362 citations recorded by the source corpus.

Summary The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many associated with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the average mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-associated microbes, and allow better exploitation of metagenomic technologies.

Subfields: Ecology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/82d18c49480ed1104f5822e01033fbdf9a015713

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Citations in the corpus

Benchmarking Metagenomics Tools for Taxonomic Classification. (2019, background): “…tools have recently identified thousands of novel metagenome assembled genomes in the human microbiome (Almeida et al., 2019; Nayfach et al., 2019; Pasolli et al., 2019) One of the biggest performance challenges for many classifiers is that they often report large numbers of low abundance false…”
Enterotypes of the human gut mycobiome (2022, background): “Current research mainly focuses on the 63 prokaryotic and viral components of the gut ecology(2-4).”
Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4 (2023, methodology): “SGBs represent both existing species (known or kSGBs) or yet-to-be-characterized species (unknown, uSGBs) defined solely based on the MAGs 42 .”
CoverM: read alignment statistics for metagenomics (2025, neutral): “…sequencing reads into metagenome assembled genomes (MAGs) has become increasingly common and high-throughput, with recovery of tens to hundreds of thousands of genomes from a diverse array of environments (Pasolli et al. 2019, Almeida et al. 2021, Nishimura and Yoshizawa 2022, Schmidt et al. 2024).”
MGnify: the microbiome analysis resource in 2020 (2019, background): “Meanwhile, research efforts focused on human gut (one of the most extensively studied biomes to date) have recently revealed unprecedented numbers of novel bacterial species with new potential functions (11– 13).”
GTDB: an ongoing census of bacterial and archaeal diversity through a phylogenetically consistent, rank normalized and complete genome-based taxonomy (2021, background): “The quality of MAGs is an ongoing concern and we are evaluating methods for decontaminating MAGs (39) and identifying and removing MAGs that may contribute to phylogenetic instability (40).”
VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences (2020, methodology): “We applied VIBRANT to identify viruses of at least 5 kb in length from 102 human gut metagenomes (discovery dataset): 49 from individuals with Crohn ’ s disease and 53 from healthy individuals [58, 59].”
Prevotella diversity, niches and interactions with the human host (2021, background): “4,886 human-associated MAGs that are assigned to the family Prevotellaceae but do not belong to any known Prevotella spp.(15).”
MetaBAT 2: an adaptive binning algorithm for robust and efficient genome reconstruction from metagenome assemblies (2019, background): “There are numerous studies that have reported using MetaBAT 2 and its associated tools for successful large scale metagenomic analyses ( Rinke et al., 2018 ; Bahram et al., 2018 ; Pasolli et al., 2019 ).”
Microbiome definition re-visited: old concepts and new challenges (2020, background): “For example, 154,723 microbial genomes of the global human microbiome were recently reconstructed from 9,428 metagenomes [112].”