A high-quality genomic catalog of the human oral microbiome broadens its phylogeny and clinical insights

Abstract Understanding the taxonomic and functional diversity of the human oral microbiome requires comprehensive genomic catalogs. We present the human reference oral microbiome (HROM), with 72,641 high-quality genomes from 3,426 species, including 2,019 novel species, significantly improving metagenomic sequence read classification over existing catalogs. Notably, HROM unveils 1,137 novel candidate phyla radiation (CPR) species, establishing Patescibacteria as the most prevalent phylum in the oral microbiota, with oral Patescibacteria forming a distinct clade from environmental Patescibacteria. We also identify an oral CPR subclade associated with periodontitis, which complement Porphyromonas gingivalis in predicting the disease. Finally, comparing HROM with reference genomes of the human gut microbiome reveals significant taxonomic and functional divergence between the oral and gut microbiomes. We identify 42 ectopic oral species and demonstrate that their relative abundance in gut microbiota is predictive of intestinal, cardiovascular, and liver diseases, highlighting the clinical importance of the oral microbiota in systemic disorders.