The oral mouse microbiome promotes tumorigenesis in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck worldwide. Dysbiosis or the microbiome has increasingly being linked to the development of different kinds of cancer. Applying 16S rDNA sequence analysis and metatranscriptomic analyses, we characterized longitudinal changes in the profiles and function of the oral microbiome, in a 4-NQO-induced model of OSCC in gnotobiotic mice. We characterized the dynamics of the oral microbiome in this model using two different microbiome inocula, one from healthy mice and the other from a mouse bearing a 4-NQO-induced tumor. Mice colonized with different oral microbiomes and exposed to 4-NQO had increased tumor numbers and size compared to controls exposed to 4-NQO but lacking a microbiome. We observed an overall increase in diversity in the tumorigenic samples when compared to the non-tumor group not exposed to 4-NQO. Despite the variability in community dynamics, specific patterns emerged during the progression of the disease. In the two groups that were inoculated with the OSCC-associated microbiome, we observed opposite profiles of abundance in Parabacteroides and Corynebacterium. While Parabacteroides decreased in percentage in the control group, it increased in the OSCC group, and the opposite was observed for Corynebacterium. The metatranscriptomic analysis revealed over-expression of the same metabolic signatures associated with OSCC regardless of the community profile. These included nitrogen transport, response to stress, inter-species interactions, Wnt pathway modulation, and aminoacids and lipid biosynthesis. Thus, these results seem to suggest that certain collective physiological activities are critical for microbiome-mediated OSCC progression.