Zhao Jingcheng, Sun Yuan-Wan, Chen Kun-Ming, Aliaga Cesar, Bisanz Jordan E, El-Bayoumy Karam
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania.
Department of Biochemistry and Molecular Biology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania.
Cancer Prev Res (Phila). 2025 Jan 6;18(1):11-21. doi: 10.1158/1940-6207.CAPR-24-0347.
While tobacco smoking is a risk factor in the development of oral squamous cell carcinoma (OSCC), only a fraction of smokers develop the disease. Compelling evidence shows that microbial community composition is associated with carcinogenesis, suggesting that the microbiome may play a role in cancer development of smokers. We previously showed that black raspberry (BRB) protects against OSCC induced by the tobacco constituent dibenzo[def,p]chrysene (DBP) via alteration of genetic and epigenetic markers in a manner consistent with its cancer preventive activity. In the present study, we conducted a mouse experiment to investigate the effects of BRB and DBP individually and in combination on the oral and gut microbiota. DBP-induced DNA damage in the mouse oral cavity is an essential step for the development of OSCC in mice. 16S rRNA gene sequencing revealed that BRB significantly increased microbial diversity and shifted microbiome composition in the gut and oral cavity, whereas DBP had no significant effect. In both gut and oral microbiota, Akkermansia muciniphila was significantly reduced after BRB treatment; however, this was not consistent with pure culture in vitro assays suggesting that the impact of BRB on A. muciniphila may be mediated through indirect mechanisms including the host or other microbes. Indeed BRB, but not DBP, was found to modulate the growth kinetics of human gut microbes in vitro including lactic acid bacteria and Bacteroides spp. The results of the current study further emphasize the interplay of microbiome and environmental factors in the development and prevention of OSCC. Prevention Relevance: Our work clearly demonstrates the modulatory impact of BRB on both gut and oral microbiomes within a DBP-induced OSCC mouse model and paves the way for future research examining a causal role of BRB-microbiota interactions at different stages of disease progression.
虽然吸烟是口腔鳞状细胞癌（OSCC）发生发展的一个风险因素，但只有一小部分吸烟者会患上这种疾病。有力证据表明，微生物群落组成与致癌作用相关，这表明微生物群可能在吸烟者的癌症发展中发挥作用。我们之前表明，黑树莓（BRB）通过改变遗传和表观遗传标记，以与其癌症预防活性一致的方式预防由烟草成分二苯并[def,p]芘（DBP）诱导的OSCC。在本研究中，我们进行了一项小鼠实验，以研究BRB和DBP单独及联合作用对口腔和肠道微生物群的影响。DBP诱导的小鼠口腔DNA损伤是小鼠OSCC发生发展的一个关键步骤。16S rRNA基因测序显示，BRB显著增加了肠道和口腔中的微生物多样性并改变了微生物群组成，而DBP没有显著影响。在肠道和口腔微生物群中，BRB处理后嗜黏蛋白阿克曼氏菌均显著减少；然而，这与体外纯培养试验不一致，表明BRB对嗜黏蛋白阿克曼氏菌的影响可能是通过包括宿主或其他微生物在内的间接机制介导的。实际上，发现BRB而非DBP在体外可调节包括乳酸菌和拟杆菌属在内的人类肠道微生物的生长动力学。本研究结果进一步强调了微生物群与环境因素在OSCC发生发展和预防中的相互作用。预防相关性：我们的工作清楚地证明了在DBP诱导的OSCC小鼠模型中BRB对肠道和口腔微生物群的调节作用，并为未来研究BRB与微生物群相互作用在疾病进展不同阶段中的因果作用铺平了道路。
