Abstract
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.
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Data availability
All data used in this study are available in the main text and supplementary materials. Sequencing data associated with this study have been deposited in NCBI under BioProject PRJNA1143182 and PRJNA1143175.
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Acknowledgements
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (RS-2022-NR067350); the National Research Foundation (NRF) funded by the Korean government (MSIT) (RS-2023-00227274); and a grant from the Mid-Career Researcher Program (RS-2025-00523268). We thank Seung Hyun Han (Seoul National University, Republic of Korea) for kindly providing the MOC2 cell line used in this study. We also thank Yui Taek Lee (Kyung Hee University, Republic of Korea) for helpful comments on the cell experiments.
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E.J.T. and J-W.B. designed the study. E.J.T., B-J.G., J-Y.L., J.E.H., Y-S.J., H-I.J., and H.J.S. carried out the experiments. Data analysis was performed by E.J.T., J-Y.L., and Y-S.J. E.J.T. drafted the manuscript, with H.S.K. and J-W.B. contributing to the revisions. All authors approved the final version of the manuscript.
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Tak, E.J., Goo, BJ., Lee, JY. et al. Dysbiosis of oral and gut microbiomes characterized by elevated Lactococcus in a mouse model of oral squamous cell carcinoma. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-00934-8
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DOI: https://doi.org/10.1038/s41522-026-00934-8
