Oral virome metagenomic catalog links Porphyromonas gingivalis phages to obesity and type 2 diabetes.

The human microbiota has a critical role in maintaining human microbiome homeostasis and health, yet the viral component of the oral microbiome remains largely unidentified. We establish the Human Oral Virome Database (HOVD) catalog, a freely accessible online resource cataloging 24,440 bacteriophage viral operational taxonomic units and 83 eukaryotic viral genomes. Utilizing HOVD, we investigate oral virome variation and its correlation with oral bacteria and gut virome in 220 obese individuals with or without type 2 diabetes mellitus (T2D). Obese individuals with T2D exhibit reduced oral viral diversity, lower correlations with clinical features, disrupted viral-bacterial correlations, and enhanced oral-gut virome transmission. Furthermore, we computationally identify bacteriophages that infect Porphyromonas gingivalis and screen six putative endolysins. Experimental validation reveals that a mixture of three endolysins significantly inhibits Porphyromonas gingivalis growth. These findings highlight the potential of phage-derived endolysins for periodontitis with T2D, offering a path toward oral and systemic disease intervention.