Growing evidence suggests that imbalances in resident microbes (dysbiosis) can promote chronic inflammation, immune-subversion, and production of carcinogenic metabolites, thus leading to neoplasia. Yet, evidence to support a direct link of individual bacteria species to human sporadic cancer is still limited. This chapter focuses on several emerging bacterial toxins that have recently been characterized for their potential oncogenic properties toward human orodigestive cancer and the presence of which in human tissue samples has been documented. These include cytolethal distending toxins produced by various members of gamma and epsilon Proteobacteria, Dentilisin from mammalian oral Treponema, Pasteurella multocida toxin, two Fusobacterial toxins, FadA and Fap2, Bacteroides fragilis toxin, colibactin, cytotoxic necrotizing factors and α-hemolysin from Escherichia coli, and Salmonella enterica AvrA. It was clear that these bacterial toxins have biological activities to induce several hallmarks of cancer. Some toxins directly interact with DNA or chromosomes leading to their breakdowns, causing mutations and genome instability, and others modulate cell proliferation, replication and death and facilitate immune evasion and tumor invasion, prying specific oncogene and tumor suppressor pathways, such as p53 and β-catenin/Wnt. In addition, most bacterial toxins control tumor-promoting inflammation in complex and diverse mechanisms. Despite growing laboratory evidence to support oncogenic potential of selected bacterial toxins, we need more direct evidence from human studies and mechanistic data from physiologically relevant experimental animal models, which can reflect chronic infection in vivo, as well as take bacterial-bacterial interactions among microbiome into consideration.

越来越多的证据表明，常驻微生物的失衡（营养不良）会促进慢性炎症，免疫破坏和致癌代谢产物的产生，从而导致瘤形成。但是，支持单个细菌物种与人类散发性癌症直接联系的证据仍然有限。本章重点介绍了几种新兴的细菌毒素，这些毒素最近因其对人原发性消化道癌的潜在致癌特性而得到了表征，并且已经在人体组织样品中进行了记录。这些包括由来自哺乳动物口服γ和ε-变形菌，Dentilisin的各种构件所产生的细胞致死肿胀毒素的梅毒螺旋，多杀性巴氏杆菌毒素，二Fusobacterial毒素，发达和FAP2，大肠杆菌，沙门氏菌中的脆弱细菌毒素，大肠菌素，细胞毒性坏死因子和α-溶血素AvrA。显然，这些细菌毒素具有生物活性，可诱发多种癌症标志。一些毒素与DNA或染色体直接相互作用，导致其分解，导致突变和基因组不稳定，另一些毒素则调节细胞增殖，复制和死亡，并促进免疫逃逸和肿瘤侵袭，撬动特定的癌基因和肿瘤抑制途径，例如p53和β-连环蛋白/ Wnt。另外，大多数细菌毒素以复杂多样的机制控制促肿瘤的炎症。尽管有越来越多的实验室证据支持选定细菌毒素的致癌潜力，但我们仍需要来自人体研究的更直接证据以及来自生理相关实验动物模型的机理数据，这些数据可以反映出体内的慢性感染，