The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma

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 characteri...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Philip Stashenko, Susan Yost, Yoonhee Choi, Theodora Danciu, Tsute Chen, Subbiah Yoganathan, Christine Kressirer, Montserrat Ruiz-Tourrella, Bikul Das, Alexis Kokaras, Jorge Frias-Lopez
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	OSCC dysbiosis metatranscriptome microbiome time series Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ccf6519815b74874a3ccb061d9808817
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ccf6519815b74874a3ccb061d9808817
record_format	dspace
spelling	oai:doaj.org-article:ccf6519815b74874a3ccb061d98088172021-12-02T19:46:18ZThe Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma10.1128/mSystems.00323-192379-5077https://doaj.org/article/ccf6519815b74874a3ccb061d98088172019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00323-19https://doaj.org/toc/2379-5077ABSTRACT 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.Philip StashenkoSusan YostYoonhee ChoiTheodora DanciuTsute ChenSubbiah YoganathanChristine KressirerMontserrat Ruiz-TourrellaBikul DasAlexis KokarasJorge Frias-LopezAmerican Society for MicrobiologyarticleOSCCdysbiosismetatranscriptomemicrobiometime seriesMicrobiologyQR1-502ENmSystems, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	OSCC dysbiosis metatranscriptome microbiome time series Microbiology QR1-502
spellingShingle	OSCC dysbiosis metatranscriptome microbiome time series Microbiology QR1-502 Philip Stashenko Susan Yost Yoonhee Choi Theodora Danciu Tsute Chen Subbiah Yoganathan Christine Kressirer Montserrat Ruiz-Tourrella Bikul Das Alexis Kokaras Jorge Frias-Lopez The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
description	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.
format	article
author	Philip Stashenko Susan Yost Yoonhee Choi Theodora Danciu Tsute Chen Subbiah Yoganathan Christine Kressirer Montserrat Ruiz-Tourrella Bikul Das Alexis Kokaras Jorge Frias-Lopez
author_facet	Philip Stashenko Susan Yost Yoonhee Choi Theodora Danciu Tsute Chen Subbiah Yoganathan Christine Kressirer Montserrat Ruiz-Tourrella Bikul Das Alexis Kokaras Jorge Frias-Lopez
author_sort	Philip Stashenko
title	The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
title_short	The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
title_full	The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
title_fullStr	The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
title_full_unstemmed	The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
title_sort	oral mouse microbiome promotes tumorigenesis in oral squamous cell carcinoma
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/ccf6519815b74874a3ccb061d9808817
work_keys_str_mv	AT philipstashenko theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT susanyost theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT yoonheechoi theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT theodoradanciu theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT tsutechen theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT subbiahyoganathan theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT christinekressirer theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT montserratruiztourrella theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT bikuldas theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT alexiskokaras theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT jorgefriaslopez theoralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT philipstashenko oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT susanyost oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT yoonheechoi oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT theodoradanciu oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT tsutechen oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT subbiahyoganathan oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT christinekressirer oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT montserratruiztourrella oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT bikuldas oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT alexiskokaras oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma AT jorgefriaslopez oralmousemicrobiomepromotestumorigenesisinoralsquamouscellcarcinoma
_version_	1718376050593890304

The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma

Ejemplares similares