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

TLDR

The human microbiome’s full diversity, especially beyond the gut and in diverse populations, remains largely uncharacterized. Using 9,428 metagenomes, the authors reconstructed 154,723 high‑quality microbial genomes covering diverse body sites, ages, countries, and lifestyles. The study identified 4,930 species‑level genome bins, 77 % of which lack public references, with 93 % of samples containing unknown genomes that enrich underrepresented phyla and non‑Westernized populations; 2.85 million genes were annotated, many linked to infant development or Westernization, and the expanded catalog raised gut read mappability from 67.8 % to 87.5 % and mouth from 65.1 % to 82.3 %, enabling deeper microbiome analyses and improved metagenomic exploitation.

Abstract

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.