The oral microbiota and oral squamous cell carcinoma
MetadataShow full item record
Background. The human oral cavity is populated by a complex microbiota, or oral microbiome, assembled from collection of over 800 bacterial phylotypes. While the majority of oral bacteria are commensals associated with oral health, the microbiome also contains known pathogens as well as bacteria in the saliva and on oral epithelial surfaces which may be associated with oral squamous cell carcinoma (OSCC). The role of the oral microbiome in OSCC and its function in the oral tumor microenvironment and tumor progression are unknown. Determination of the microbiome composition within the oral tumor microenvironment may reveal shifts in the microbiome population and reveal bacteria with roles in carcinogenesis and disease progression. Objectives. To determine the tumor tissue microenvironment ecology of the human oral microbial community in oral precancerous and cancerous lesions in comparison with tissue collected from the oral mucosa of clinically healthy individuals and those with periodontitits. Methods. We used phylogenetic 16S rRNA analysis and bioinformatics to characterize and compare the microbiota of 39 patients with healthy oral tissue, tissues collected from periodontitis and progressive primary and recurrent tumors, including precancerous and cancerous lesions. Bacteria were visualized within sections of the healthy and cancer tissue by performing fluorescent in situ hybridization with the universal oligonucleotide probe and counterstained with epithelial staining (AE1/3) or leukocyte staining (CD45). Bacterial loading (16S rRNA) was determined. Viable bacteria were also isolated and identified by 16S analysis, and bacterial invasion assays were performed using the oral epithelium carcinoma cell line (A253), in vitro. Results. Tumor groups were associated with phylum-level changes in the microbiota, increased bacterial richness and diversity as well as a ∼20% increase of unculturable bacteria not previously identified in the oral microbiome. Moreover, the cancer tissue microenvironment harbored an abundance of bacteria, some of which are viable and able to invade epithelium from clinical sources as well as oral cancer cell lines. In addition, the microbiota richness of periodontitis is intermediate between health and cancer. In addition, the microbiota of periodontitis was more similar to cancer than was the microbiota of periodontitis and healthy, and the microbiota of healthy and that of cancer. Conclusion. This is the first study of the microbiota within the oral tumor microenvironment which not only demonstrates a link between the microbiome of periodontitis, oral cancer and tumor progression, but also suggests the possible use of cancer associated bacterial phylotypes as predictive biomarkers of oral cancer.