The salivary virome during childhood dental caries

Abstract

While many studies have examined the bacterial taxa associated with dental caries, the most common chronic infectious disease globally, little is known about the caries-associated virome. In this study, the salivary viromes of 21 children with severe caries (>2 dentin lesions) and 23 children with healthy dentition were examined. 2,485 viral metagenome-assembled genomes (vMAGs) were identified, binned, and quantified from the metagenomic assemblies. These vMAGs were mostly phage, and represented 1,547 unique species-level vOTUs, 247 of which appear to be novel. The metagenomes were also queried for all 3,835 unique species-level vOTUs of DNA viruses with a human host on NCBI Virus, however all but Human betaherpesvirus 7 were at very low abundance in the saliva. The oral viromes of the children with caries exhibited significantly different beta diversity compared to the oral virome of the children with healthy dentition; several vOTUs predicted to infect Pauljensenia and Neisseria were strongly correlated with health, and two vOTUs predicted to infect Saccharibacteria and Prevotella histicola, respectively, were correlated with caries. Co-occurrence analysis indicated that phage typically co-occurred with both their predicted hosts and with bacteria that were themselves associated with the same disease status. Overall, this study provided the sequences of 53 complete or nearly complete novel oral phages and illustrated the significance of the oral virome in the context of dental caries, which has been largely overlooked. This work represents an important step towards the identification and study of phage therapy candidates which treat or prevent caries pathogenesis. ImportanceDental caries is the most common chronic infectious disease, worldwide, and is caused by a dysbiosis of the oral microbiome featuring an increased abundance of acid-tolerant, acid-producing, and biofilm-forming bacteria. The oral microbiome also contains viruses; however, very little is known about the the caries-associated virome. In this study, the salivary virome of children with severe caries was compared to the salivary virome of children with healthy dentition. The metagenomes contained a total of 1,547 unique species-level vOTUs, 247 of which appeared to be novel. The viromes from the children with caries were significantly different than the viromes from the children with healthy teeth, and several health- and disease-associated vOTUs were identified. This study illustrated the importance of the oral virome in the context of dental caries, and serves as a step towards a better understanding of oral inter-kingdom interactions and identification of potential phage-based caries therapeutics.