Lamont Richard J, Fitzsimonds Zackary R, Wang Huizhi, Gao Shegan
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA.
Department of Oral and Craniofacial Molecular Biology, VCU School of Dentistry, Richmond, Virginia, USA.
Periodontol 2000. 2022 Jun;89(1):154-165. doi: 10.1111/prd.12425. Epub 2022 Mar 4.
Oral and esophageal squamous cell carcinomas harbor a diverse microbiome that differs compositionally from precancerous and healthy tissues. Though causality is yet to be definitively established, emerging trends implicate periodontal pathogens such as Porphyromonas gingivalis as associated with the cancerous state. Moreover, infection with P. gingivalis correlates with a poor prognosis, and P. gingivalis is oncopathogenic in animal models. Mechanistically, properties of P. gingivalis that have been established in vitro and could promote tumor development include induction of a dysbiotic inflammatory microenvironment, inhibition of apoptosis, increased cell proliferation, enhanced angiogenesis, activation of epithelial-to-mesenchymal transition, and production of carcinogenic metabolites. The microbial community context is also relevant to oncopathogenicity, and consortia of P. gingivalis and Fusobacterium nucleatum are synergistically pathogenic in oral cancer models in vivo. In contrast, oral streptococci, such as Streptococcus gordonii, can antagonize protumorigenic epithelial cell phenotypes induced by P. gingivalis, indicating functionally specialized roles for bacteria in oncogenic communities. Consistent with the notion of the bacterial community constituting the etiologic unit, metatranscriptomic data indicate that functional, rather than compositional, properties of the tumor-associated communities have more relevance to cancer development. A consistent association of P. gingivalis with oral and orodigestive carcinoma could have diagnostic potential for early detection of these conditions that have a high incidence and low survival rates.
口腔和食管鳞状细胞癌具有多样的微生物群，其组成与癌前组织和健康组织不同。尽管因果关系尚未最终确定，但新出现的趋势表明，诸如牙龈卟啉单胞菌等牙周病原体与癌症状态有关。此外，感染牙龈卟啉单胞菌与预后不良相关，并且牙龈卟啉单胞菌在动物模型中具有致癌性。从机制上讲，已在体外确定的、可促进肿瘤发展的牙龈卟啉单胞菌特性包括诱导生态失调的炎症微环境、抑制细胞凋亡、增加细胞增殖、增强血管生成、激活上皮-间质转化以及产生致癌代谢物。微生物群落背景也与致癌性相关，在体内口腔癌模型中，牙龈卟啉单胞菌和具核梭杆菌的联合体具有协同致病性。相比之下，诸如戈登链球菌等口腔链球菌可拮抗由牙龈卟啉单胞菌诱导的促肿瘤上皮细胞表型，这表明细菌在致癌群落中具有功能上的特殊作用。与细菌群落构成病因单位的观点一致，宏转录组数据表明，肿瘤相关群落的功能特性而非组成特性与癌症发展更相关。牙龈卟啉单胞菌与口腔和口腔消化系统癌症的持续关联可能对这些发病率高且生存率低的疾病的早期检测具有诊断潜力。
