J Cancer 2022; 13(10):3051-3060. doi:10.7150/jca.75947 This issue

Research Paper

Microbiome dysbiosis inhibits carcinogen-induced murine oral tumorigenesis

Yuh-Ling Chen1✉, Kuan-Chih Huang1, Jer-Horng Wu2, Tsunglin Liu3, Jiung-Wen Chen2, Jia-Yan Xie1, Meng-Yen Chen1, Li-Wha Wu4, Chun-Liang Tung5✉

1. Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
2. Department of Environmental Engineering, National Cheng Kung University, Tainan, Taiwan.
3. Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan.
4. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
5. Department of Oral Maxillo-Facial Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60080, Taiwan.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Chen YL, Huang KC, Wu JH, Liu T, Chen JW, Xie JY, Chen MY, Wu LW, Tung CL. Microbiome dysbiosis inhibits carcinogen-induced murine oral tumorigenesis. J Cancer 2022; 13(10):3051-3060. doi:10.7150/jca.75947. Available from https://www.jcancer.org/v13p3051.htm

File import instruction


Graphic abstract

Oral cancer is one of the most common cancers worldwide and ranks fourth for the mortality rate of cancers in males in Taiwan. The oral microbiota is the microbial community in the oral cavity, which is essential for maintaining oral health, but the relationship between oral tumorigenesis and the oral microbiota remains to be clarified. This study evaluated the effect of microbiome dysbiosis on oral carcinogenesis in mice, and the impact of the microbiome and its metabolic pathways on regulating oral carcinogenesis. We found that antibiotics treatment decreases carcinogen-induced oral epithelial malignant transformation. Microbiome analysis based on 16S rRNA gene sequencing revealed that the species richness of fecal specimens was significantly reduced in antibiotic-treated mice, while that in the salivary specimens was not decreased accordingly. Differences in bacterial composition, including Lactobacillus animalis abundance, in the salivary samples of cancer-bearing mice was dramatically decreased. L. animalis was the bacterial species that increased the most in the saliva of antibiotic-treated mice, suggesting that L. animalis may be negatively associated with oral carcinogenesis. In functional analysis, the microbiome in the saliva of the tumor-bearing group showed greater potential for polyamine biosynthesis. Immunochemical staining proved that spermine oxidase, an effective polyamine oxidase, was upregulated in mouse oral cancer lesions. In conclusion, oral microbiome dysbiosis may alter polyamine metabolic pathways and reduce carcinogen-induced malignant transformation of the oral epithelium.

Keywords: microbiota, oral cancer, antibiotics-induced microbiome dysbiosis, polyamine, spermine oxidase