Figure 2.

Mechanisms linked between oral microbiome and carcinogenesis. 1. Impairment of barrier function. Bacteria induced impairment of epithelial barrier function, which increases the exposure of immune cells to bacterial endotoxins and antigens and future leads to cancer progression. 2. Synthesis of carcinogenic metabolites and bacterial toxins. Microbial metabolites, including sulfides, nitrosamines, hydroxyl radical, ACH and DCA, and bacterial toxins, such as CDT and colibactin, can further induce DNA damage and trigger oncogenesis. 3. Induction of inflammation. ROS and cytokines produced by inflammatory cells are believed to contribute to initiation of cancer by inducing mutations, genomic instability, and epigenetic alterations. 4. Activation of cell proliferation. FadA of F.n. binds to E-cadherin on colorectal carcinoma (CRC) cells and activates β-catenin signaling and subsequently enhanced CRC cell proliferation. A.a., Aggregatibacter actinomycetemcomitans; ACH, acetaldehyde; DCA, deoxycholic acid; CDT, cytolethal distending toxin; F.n., Fusobacterium nucleatum; P.g., Porphyromonas gingivalis; ROS, reactive oxygen species; S.g., Streptococcus gordonii.