Vendor-Specific Microbiomes Influence Oral Cancer Development and Its Response to a Bacterial Intervention in Mice

Background The role of microbiota as a double-edged sword in cancer is increasingly recognized. Our previous in vitro studies demonstrate that Streptococcus mitis possesses anticancer properties against oral cancer cell lines. In this study, we aimed to validate these findings in the 4-NQO (4-nitroquinoline 1-oxide) induced oral cancer mouse model. Given that mice from different vendors harbor distinct microbiomes, which can influence disease and experimental outcomes, we also assessed whether vendor-specific oral and/or gut microbiome differences affect susceptibility to oral carcinogenesis as well as the response to S. mitis intervention. Results Significant baseline differences in the oral and gut microbiomes were observed between Jackson and Taconic mice. 4-NQO treatment resulted in marked shifts in microbial diversity and partial convergence of microbiome profiles between vendor groups by week 8. Histopathological evaluation at week 32 revealed a significantly higher burden of squamous cell carcinoma (SCC) in Jackson mice. Several oral and fecal microbial taxa were significantly associated with SCC burden, most notably the genus Clostridium , which was enriched in both the oral and fecal microbiomes of Jackson mice. Despite transient colonization, S. mitis intervention reduced SCC burden in both mouse cohorts and was associated with modest microbial changes, including a reduction in Clostridium abundance. Conclusions These findings support further investigation into S. mitis as a potential anticancer agent and highlights the importance of accounting for baseline microbiome differences in preclinical cancer models.