Identification of beneficial symbiont candidates in commensalism as potential oral gatekeepers

The basis of the development of oral cancer has been reported to be inflammation (e.g., periodontitis) caused by dysbiosis of the oral microbiota (i.e., a decrease in beneficial oral symbionts). Since a decrease in beneficial symbionts is connected to oral cancer, restoring these bacteria may help prevent it. Based on this, oral probiotics using beneficial oral symbionts are under development. Therefore, it is necessary to understand how beneficial oral symbionts are maintained in a healthy oral cavity. We evaluated a cohort consisting of 42 healthy volunteers and 39 oral cancer patients via 16S metagenomic analysis. Beneficial symbiont candidates were mined by comparing the oral microbiota of healthy volunteers with that of oral cancer patients, and the interaction mode among the beneficial symbiont candidates was further examined. Cancer patients exhibited decreased relative abundance of the genera <i>Rothia</i> and <i>Streptococcus</i>. In addition, both bacterial genera further decreased in advanced cancer, highlighting them as beneficial candidates. Furthermore, these two bacterial genera demonstrated a positive correlation in terms of relative abundance. <i>Rothia dentocariosa</i> isolated from a representative healthy volunteer was suggested to support the survival of <i>Streptococcus salivarius</i> through possible syntrophic interaction. Thus, we report a potential syntrophic interaction between <i>Streptococcus</i> spp. and <i>Rothia</i> spp. as a possible mechanism underlying oral health maintenance. Given that <i>S. salivarius</i> is currently employed as an oral probiotic, our findings provide insights into the development of probiotics for oral cancer.IMPORTANCEPathobiont candidates associated with oral cancer are currently being thoroughly investigated. However, it is not clear which bacteria and how their interactions contribute to preventing the development of oral cancer. In this report, we demonstrate for the first time the presence of a potential syntrophic interaction between <i>Rothia</i> spp. and <i>Streptococcus</i> spp., both of which were identified as beneficial symbiont candidates in the oral cavity.