Vendor-specific microbiomes influence oral cancer development and its response to Streptococcus mitis intervention in mice

Background: We previously demonstrated that Streptococcus mitis exhibits anticancer properties in vitro. Here, we sought to validate these findings in vivo. Because mice from different vendors harbor distinct microbiomes that can influence disease susceptibility and experimental outcomes, we also examined whether vendor-specific oral and gut microbiomes affect oral carcinogenesis and response to S. mitis intervention. Materials and methods: Oral carcinogenesis was induced using 4-NQO in C57BL/6 mice from Jackson Laboratory and Taconic Biosciences (n = 32 per vendor). Mice were randomized to biweekly oral swabbing with S. mitis or vehicle for 28 weeks. Oral and fecal microbiomes were profiled at baseline and week 8. At week 32, tongues were evaluated for tumor development. Results: Oral and gut microbiomes differed significantly between vendors. 4-NQO exposure induced marked microbial shifts and partial convergence of microbiome profiles. Jackson mice developed a significantly higher squamous cell carcinoma (SCC) burden. Several microbial taxa were associated with SCC, notably Clostridium, which was enriched in oral and fecal samples from Jackson mice. S. mitis reduced SCC burden in both cohorts and was accompanied by decreased Clostridium abundance. Conclusions: These data support S. mitis as a potential anticancer agent and underscore the importance of microbiome context in preclinical cancer models.