The effect of oral microbiota on the oral carcinogenesis

Abstract

Oral cancer is the fifth most common cancer in the worldwide and ranks fourth in Taiwan for male cancer mortality The human microbiota is the aggregate of microorganisms that resides on or within any of human tissue and biofluids Oral cavity has more than 25 000 bacteria which are closely to the health of oral cavity For example Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are associated with periodontal disease and Streptococcus mutans is associated with caries But the relationship between oral cancer and oral microbiota is still unclear In this study we first evaluated the effect of antibiotics in carcinogen-induced oral cancer mouse model The results showed that 4-nitroquinoline 1-oxide (4-NQO)/arecoline-induced oral epithelial hyperplasia are increased in antibiotic-treated group (n =9) than control mice (n = 10) But interestingly malignant transformation rate was obviously decreased in antibiotic-treated group (0/9) compared with control group (3/10) We also analyzed the microbiota of murine saliva by next-generation sequencing (NGS) and compared the alteration of microbiota between control versus antibiotics-treated group and tumor-bearing versus no-tumor-bearing mice The data showed that the diversity of microbiota was decreased in tumor bearing mice Lactobacillus sp was the most increased in the antibiotic treated group and also the most decreased in the tumor-bearing mice Moreover we also investigated the effect of human oral verrucous hyperplasia-associated bacteria Streptococcus anginosus on human oral cancer cells We found that some tumor proliferation and migration mediators of oral cancer cells were suppressed by Streptococcus anginosus treatment The proliferation and migration ability were significantly inhibited after Streptococcus anginosus co-culture but not by heat-inactivated Streptococcus anginosus The effect of Streptococcus anginosus on oral cancer formation was investigated in xenograft mouse models by a subcutaneous injection of Streptococcus anginosus-treated OC2 cells into NOD-SCID mice The results indicated that tumor growth of OC2 was suppressed after co-culturing Streptococcus anginosus Therefore we considered that Streptococcus anginosus was a preventive microbiome in oral carcinogenesis Clarifying the effects and mechanisms of oral bacteria on the oral tumorigenesis will help prevent and understand the malignant transformation of oral cancer

Date of Award	2020
Original language	English
Supervisor	Yuh-Ling Chen (Supervisor)