[ODP-018/WS4-8] 唾液のショットメタゲノム解読による口腔疾患微生物と遺伝子の同定
Medication-related osteonecrosis of the jaw (MRONJ) is an oral disease in which infection is suggested. Prior studies that explored the association between MRONJ and microbial infection were limited to the culture-based approach or 16S ribosomal RNA gene sequencing. Here, deep shotgun metagenome sequencing (>10 Gb per sample) of bulk DNA extracted from saliva of MRONJ patients and healthy controls was performed to overcome these limitations. Comparative quantitative analyses of these deep metagenomes revealed an average 10.1% increase of genus Actinomyces and a 33.2% decrease in genus Streptococcus. Pan-genome analysis identified genes present exclusively in the MRONJ samples. Further analysis of the reads mapping to the genes in an extended dataset resulted in the identification of 31 genes significantly associated with MRONJ. All these genes were encoded by Actinomyces genomic regions. Of these, the top two abundant genes were almost exclusively encoded by Actinomyces among usual taxa in the human oral microbiota. The potential relationships of these key genes with the disease are discussed at molecular level based on the literature. Although the sample size was small, this study will aid future studies to verify the data and characterize these genes to understand the disease mechanisms, develop molecular targeted drugs, and for early stage screening (PLOS One, in press).