Dysbiosis of oral and gut microbiomes characterized by elevated Lactococcus in a mouse model of oral squamous cell carcinoma

Oral microorganisms contribute to the progression of oral squamous cell carcinoma (OSCC), and the gut microbiome may also influence OSCC by modulating systemic immunity. This study investigated oral and gut microbial changes in a 4-nitroquinoline N-oxide (4-NQO)-induced OSCC mouse model. After 16 weeks of 4-NQO exposure, significant alterations were observed in the beta diversity of both oral and gut microbiomes. Notably, the relative abundance of Lactococcus increased, especially in oral microbiomes, from week 6 to 16, followed by a decline at week 22, suggesting a 4-NQO-induced niche favorable to its proliferation. Absolute quantification revealed a 4-NQO-induced increase in total bacterial load in the oral cavity, accompanied by elevated absolute abundance of Lactococcus. Unexpectedly, oral administration of Lactococcus strains isolated from 4-NQO-treated mice mildly alleviated inflammation. In vitro, lysates from these strains exhibited protein-dependent cytotoxicity against murine OSCC cells. These results suggest that Lactococcus strains may exert protective effects during OSCC progression.