Integrating metagenomics and cultivation unveils oral phage diversity and potential impact on hosts.

Bacteriophages play important roles in the regulation of bacterial communities and may thus impact human health. However, the scarcity of genomic data of oral microorganism has limited information on oral phages. We collected data on 5427 metagenomic samples and 2178 cultivated bacterial genomes across different geographical areas and populations, generating the Oral Phage Database (OPD), comprising 189,859 representative phage genome sequences, including 3416 huge phages (genome size > 200 kbp). OPD reveals that most oral viruses are unknown and encode an enormous variety of dark proteins. Numerous oral phages infecting a broad range of hosts carry anti-defense genes, auxiliary metabolic genes, and virulence factors that may affect bacterial metabolism and influence human health. The composition of oral phages varies among different populations, and several phages have the potential to act as biomarkers for disease. OPD expands our knowledge of phage-bacteria interactions, huge phages diversity, and potential impacts on human health.