Fig. 4.

Oral microbial dysbiosis is associated with oral cancer development through different mechanisms. A - Oral infections and dysbiosis are responsible for promoting a pro-inflammatory microenvironment, wherein inflammatory cytokines and matrix metalloproteinases favor the development and progression of tumors. Furthermore, the bacteria in the oral cavity produce oxygen and nitrogen reactive species, as well as oncogenic metabolites (e.g., nitrosamines) to induce genetic damage to cells within the oral mucosa. Another mechanism by which neoplastic transformation is mediated by oral dysbiosis is via the alteration of epithelial barriers, which predispose the oral mucosa to the development of chronic pre-cancerous lesions. Oral dysbiosis is responsible for several epigenetic alterations, which promote the development of tumors (e.g., alteration of onco-miR or DNA methylation phenomena). Figure reprinted from “Association of oral dysbiosis with oral cancer development” by La Rosa et al[121] licensed under CC BY 4.0; no changes were made to the figure. B - A recent report by Kamarajan et al[268] documents an in vivo model in which periodontal pathogens, i.e. Treponema denticola (ATCC 35405), Porphyromonas gingivalis (ATCC 33277) and Fusobacterium nucleatum (ATCC 25586) and, their lipopolysaccharides activate TLR/MyD88-Integrin/FAK cross talk to promote cancer cell migration and invasion. Interestingly, nisin Z (Handary, Belgium), a bacteriocin produced by Lactococcus lactis inhibits the cancer formation. Image courtesy of Drs. Pachiyappan Kamarajan and Ryutaro Kuraji.