The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma

mSystems

Philip Stashenko¹  Bikul Das²  Jorge Frias-Lopez³  Theodora Danciu⁴  Alexis Kokaras⁵  Susan Yost⁵  Tsute Chen⁵  Subbiah Yoganathan⁵  Yoonhee Choi⁵  Christine Kressirer⁵  Montserrat Ruiz-Tourrella⁵ 

[1] Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts, USA;Department of Cancer and Stem Cell Biology, Thoreau Lab for Global Health, University of Massachusetts—Lowell, Lowell, Massachusetts, USA;Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USA;Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA;Forsyth Institute, Cambridge, Massachusetts, USA;

关键词: OSCC;    dysbiosis;    metatranscriptome;    microbiome;    time series;   

DOI  :  10.1128/mSystems.00323-19

来源: DOAJ

【 摘 要 】

ABSTRACT Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck worldwide. Dysbiosis of the microbiome has increasingly been linked to the development of different kinds of cancer. Applying 16S rRNA gene sequence analysis and metatranscriptomic analyses, we characterized the longitudinal changes in the profiles and the function of the oral microbiome in a 4-nitroquinoline-1-oxide (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 mice bearing a 4-NQO-induced tumor. Mice colonized with different oral microbiomes and exposed to 4-NQO had increased tumor numbers and sizes compared to controls exposed to 4-NQO but lacking a microbiome. We observed an overall increase in diversity in the tumorigenic samples compared to that in the nontumor 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 the percentage of Parabacteroides bacteria decreased in the control group, it increased in the OSCC group, and the opposite was observed for Corynebacterium. The metatranscriptomic analysis revealed overexpression of the same metabolic signatures associated with OSCC regardless of the community profile. These included nitrogen transport, response to stress, interspecies interactions, Wnt pathway modulation, and amino acid and lipid biosynthesis. Thus, these results seem to suggest that certain collective physiological activities are critical for microbiome-mediated OSCC progression. IMPORTANCE There is growing evidence that changes in the microbiome are associated with carcinogenesis. To date, no consistent oral microbiome composition associated with OSCC has been identified. Longitudinal and functional studies like the study presented here should yield a better understanding of the role that the oral microbiome plays in OSCC. Our findings, obtained using a germ-free mouse model, indicate that the presence of different oral microbiomes enhances tumorigenesis and increases the final number of tumors in mice. By studying community-wide expression profiles, we found that regardless of the phylogenetic composition of the microbiome, the same metabolic activities were consistently associated with OSCC. Therefore, due to the functional redundancy of the microbiome, the critical element in explaining the contribution of the microbiota in OSCC is the collective physiological activity of the community, thus accounting for the previous inability to identify a consensus community profile or etiologic agents for OSCC.

【 授权许可】

Unknown