Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses
Open accessAbstract
Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients. A search of the oral microbiome has revealed a group of bacteria closely associated with the most common type of oral cancer, and whose activity may play a role in its development. Oral squamous cell carcinoma (OSCC) has been linked to tobacco and alcohol consumption, but there’s increasing interest in the role bacteria might play in its initiation and growth. To better understand the behaviour of the various microbes present in the mouths of healthy people and those with OSCC, Jorge Frias-Lopez at the University of Florida in Gainesville and his colleagues carried out a metatranscriptome analysis, which identifies the most actively expressed genes. This revealed significant differences in their microbial communities, with Fusidobacteria particularly enriched and hyperactive in patients with OSCC. The team also identified microbial activities that were consistently associated with cancer.
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Various disease states are associated with the oral microbiome, including caries, periodontal disease, oral, esophageal, pancreatic, and colorectal cancers, cardiovascular disease, and inflammatory bowel disease.
“This is demonstrated by the association of various disease states with the oral microbiome, including not only caries and periodontal disease but also oral, esophageal, pancreatic, and colorectal cancers, cardiovascular disease, and inflammatory bowel disease.147, 148, 149, 150, 151, 152, 153”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [147]
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Zhang, Y., Thompson, K. N., Branck, T. A., Yan, Y., Nguyen, L. H., Franzosa, E. A., & Huttenhower, C. (2021) · Annual Review of Biomedical Data Science · doi:10.1146/annurev-biodatasci-031121-103035 · Cited by 136 · see citing works
Periodontitis and risk of cancer: Mechanistic evidence
Baima, G., Minoli, M., Michaud, D. S., Aimetti, M., Sanz, M., Loos, B. G., & Romandini, M. (2023) · Periodontology 2000 · doi:10.1111/prd.12540 · Cited by 131 · see citing works
Association of oral dysbiosis with oral cancer development (Review)
Rosa, G. R. M. L., Gattuso, G., Pedull�, E., Rapisarda, E., Nicolosi, D., & Salmeri, M. (2020) · Oncology Letters · doi:10.3892/ol.2020.11441 · Cited by 125 · see citing works
“In addition, Yost et al (117) performed a preliminary meta-transcriptomic study in order to analyze the oral microbiome in oral squamous cell carcinoma patients and establish the connection with the molecular features of this tumor.”
InfluentialDysbiosis of Oral Microbiota During Oral Squamous Cell Carcinoma Development
Sarkar, P., Malik, S., Laha, S., Das, S., Bunk, S., Ray, J. G., Chatterjee, R., & Saha, A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.614448 · Cited by 117 · see citing works
“using metatranscriptomic analyses suggested importance of these pathways for OSCC development (71), so far there are no robust studies that directly linked microbes with these pathways in a tumor microenvironment.”
BackgroundFusobacteria modulate oral carcinogenesis and promote cancer progression
Harrandah, A. M., Chukkapalli, S. S., Bhattacharyya, I., Progulske‐Fox, A., & Chan, E. K. L. (2020) · Journal of Oral Microbiology · doi:10.1080/20002297.2020.1849493 · Cited by 112 · see citing works
“Biofilms on OSCCs are also reported to be rich with anaerobic bacteria associated with periodontal disease [13,14].”
BackgroundUnderstanding human health through metatranscriptomics
Ojala, T., Kankuri, E. M., & Kankainen, M. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.02.002 · Cited by 107 · see citing works
Sami, A., Elimairi, I., Stanton, C., Ross, R. P., & Ryan, C. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218061 · Cited by 105 · see citing works
“Metatranscriptomic analysis of the OSCC-associated microbiome or “oncobiome” has shown the specific activities that are undertaken by these bacteria such as increased metal ion transport and nitrous oxide reductase, as well as tryptophanase and protease activity [38].”
BackgroundResultBiological biomarkers of oral cancer
Radaic, A., Kamarajan, P., Cho, A., Wang, S., Hung, G., Najarzadegan, F., Wong, D. T., Ton‐That, H., Wang, C., & Kapila, Y. L. (2023) · Periodontology 2000 · doi:10.1111/prd.12542 · Cited by 99 · see citing works
The Microbiome of Oral Squamous Cell Carcinomas: a Functional Perspective
Al-Hebshi, N. N., Borgnakke, W. S., & Johnson, N. W. (2019) · Current Oral Health Reports · doi:10.1007/s40496-019-0215-5 · Cited by 93 · see citing works
Association or Causation? Exploring the Oral Microbiome and Cancer Links
Teles, F., Alawi, F., CASTILHO, R. M., & Wang, Y. (2020) · Journal of Dental Research · doi:10.1177/0022034520945242 · Cited by 87 · see citing works
“Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence actors in the oral microbiome of OSCC patients (Yost et al. 2018).”
BackgroundThe Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies
Huybrechts, I., Zouiouich, S., Loobuyck, A., Vandenbulcke, Z., Vogtmann, E., Pisanu, S., Iguacel, I., Scalbert, A., Indave, I., Smelov, V., et al. (2020) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-20-0288 · Cited by 80 · see citing works
The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
Stashenko, P., Yost, S. C., Choi, Y., Danciu, T., Chen, T., Yoganathan, S., Kressirer, C. A., Ruiz-Tourrella, M., Das, B., Kokaras, A. S., et al. (2019) · mSystems · doi:10.1128/msystems.00323-19 · Cited by 80 · see citing works
“In a pilot study comparing the metatranscriptomes of healthy versus OSCC-associated microbiomes in human cancer, we also found that metabolic activities associated with antioxidant systems were enriched in the tumor sites (16).”
BackgroundSelf-citationOral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma
Torralba, M., Aleti, G., Li, W., Moncera, K. J., Lin, Y.-H., Yu, Y., Masternak, M. M., Golusiński, W., Golusiński, P., Lamperska, K. M., et al. (2020) · Microbial Ecology · doi:10.1007/s00248-020-01596-5 · Cited by 75 · see citing works
“More recent transcriptomics analysis by Yost et al. (2018) supports the role that Fusobacterium may have in the development of OSCC, showing a higher number of fusobacterial transcripts in tumor adjacent samples [39].”
BackgroundFrom Beyond the Pale to the Pale Riders: The Emerging Association of Bacteria with Oral Cancer
Fitzsimonds, Z. R., Hernandez, C. J. R., Bagaitkar, J., & Lamont, R. J. (2020) · Journal of Dental Research · doi:10.1177/0022034520907341 · Cited by 74 · see citing works
“OSCC tumors found metabolic activities better correlated with disease than did community microbial composition (Yost et al. 2018), and a comparison of microbiotas associated with OSCC in different countries revealed functional rather than compositional similarities (Perera et al.”
BackgroundOral cavity cancer in young, non-smoking, and non-drinking patients: A contemporary review
Tran, Q., Maddineni, S., Arnaud, E. H., Divi, V., Megwalu, U. C., Topf, M. C., & Sunwoo, J. B. (2023) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2023.104112 · Cited by 73 · see citing works
Liu, W., Cui, Y., Wei, J., Sun, J., Zheng, L., & Xie, J. (2020) · International Journal of Oral Science · doi:10.1038/s41368-020-0086-6 · Cited by 73 · see citing works
Metabolites of the oral microbiome: important mediators of multikingdom interactions
Barbour, A., Elebyary, O., Fine, N. A., Oveisi, M., & Glogauer, M. (2021) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuab039 · Cited by 68 · see citing works
Pathogenesis of periodontitis – A potential role for epithelial-mesenchymal transition
Saliem, S. S., Bede, S. Y. H., Cooper, P. R., Abdulkareem, A. A., Milward, M. R., & Abdullah, B. H. (2022) · Japanese Dental Science Review · doi:10.1016/j.jdsr.2022.09.001 · Cited by 74 · see citing works
“Phosphorylation of Akt, and its consequent activation, also induces NF-κB signaling which increases the transcription of several anti-apoptotic genes in GECs [177].”
MethodInfluentialThe Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics in Oral Cancer Management
Fuad, A. S. M., Amran, N. A., Nasruddin, N. S., Burhanudin, N. A., Dashper, S. G., & Arzmi, M. H. (2022) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-022-09985-7 · Cited by 63 · see citing works
“This finding is also suggestive that Fusobacteria virulence factors play a role in oral cancer pathogenesis [56].”
BackgroundRole of oral microbiome in oral oncogenesis, tumor progression, and metastasis
Li, R., Li, X., Gong, T., Liu, J., Li, Y., Zhou, X., Li, Y., & Zheng, X. M. (2022) · Molecular Oral Microbiology · doi:10.1111/omi.12403 · Cited by 65 · see citing works
Saliva – a new opportunity for fluid biopsy
Huang, Z., Yang, X., Huang, Y., Tang, Z., Chen, Y., Liu, H., Huang, M., Qing, L., Li, L., Wang, Q. L., et al. (2022) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2022-0793 · Cited by 54 · see citing works
Granato, D. C., Neves, L. X., Trino, L. D., Carnielli, C. M., Busso-Lopes, A. F., Yokoo, S., Pauletti, B. A., Domingues, R. R., SÁ, J. D. O., Persinoti, G., et al. (2021) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2021.140659 · Cited by 50 · see citing works
Oral Microbiota—A New Frontier in the Pathogenesis and Management of Head and Neck Cancers
Metsäniitty, M., Hasnat, S., Salo, T. A., & Salem, A. (2021) · Cancers · doi:10.3390/cancers14010046 · Cited by 49 · see citing works
“[28] RNA amplification Oral swab samples 15 (4 OSCC; 11 OSCC-free sites/healthy individuals) Active communities in tumor/tumorfree areas Illumina adapter-specific primers were used to amplify the cDNA generated from mRNA”
MethodA Literature Review of the Potential Diagnostic Biomarkers of Head and Neck Neoplasms
Konings, H., Stappers, S., Geens, M., Winter, B. Y. D., Lamote, K., van Meerbeeck, J. P., Specenier, P. M., Vanderveken, O. M., & Ledeganck, K. J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01020 · Cited by 46 · see citing works
Wei, W., Li, J., Shen, X., Lyu, J., Yan, C., Tang, B., Ma, W., Xie, H., Жао, Л., Cheng, L., et al. (2022) · mSystems · doi:10.1128/msystems.00469-22 · Cited by 45 · see citing works
Saxena, R., K., V. P. P., Gupta, S., Gupta, S., Waiker, P., Samaiya, A., Sharma, A. K., & Sharma, V. K. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.841465 · Cited by 41 · see citing works
Triarico, S., Agresti, P., Rinninella, E., Mele, M. C., Romano, A., Attinà, G., Maurizi, P., Mastrangelo, S., & Ruggiero, A. (2022) · Pathogens · doi:10.3390/pathogens11040448 · Cited by 42 · see citing works
“In patients with cancer, the microbial host homeostasis may be disrupted by cancer itself, by the bactericidal effect of chemotherapy and antibacterial agents adopted against secondary infections, but also by the immunodeficiency induced by chemotherapy [37].”
BackgroundGugnacki, P., & Sierko, E. (2021) · Cancers · doi:10.3390/cancers13235902 · Cited by 39 · see citing works
Singh, D., Khan, M. A., & Siddique, H. R. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120008 · Cited by 36 · see citing works
Lou, F., Yan, L., Luo, S., Dong, Y., Xu, J., Kang, N., Wang, H., Liu, Y., Pu, J., Yang, B., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-333479 · Cited by 38 · see citing works
Zhou, J., Wang, L., Yuan, R., Yu, X., Chen, Z., Yang, F., Sun, G., & Dong, Q. (2020) · Cancer Management and Research · doi:10.2147/cmar.s251021 · Cited by 35 · see citing works
The Application of High-Throughput Technologies for the Study of Microbiome and Cancer
Wei, L., Cheong, I. H., Yang, G., Li, X. G., Kozlakidis, Z., Ding, L., Liu, N. N., & Wang, H. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.699793 · Cited by 35 · see citing works
Salivary Microbiota Composition in Patients with Oral Squamous Cell Carcinoma: A Systematic Review
Mauceri, R., Coppini, M., Vacca, D., Bertolazzi, G., Panzarella, V., Fede, O. D., Tripodo, C., & Campisi, G. (2022) · Cancers · doi:10.3390/cancers14215441 · Cited by 35 · see citing works
“Besides saliva, some authors have also analysed subgingival plaque, healthy, and tumour tissue [28,29,38].”
BackgroundMethodPeriodontal Pathogens: A Crucial Link Between Periodontal Diseases and Oral Cancer
Li, T., Hao, Y., Tang, Y., & Liang, X. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.919633 · Cited by 34 · see citing works
“These metabolic activities include iron acquisition, response to oxidative stress, and peptidase activity (Yost et al., 2018).”
BackgroundKhan, M. M., Frustino, J. L., Villa, A., Nguyen, B.-C., Woo, S., Johnson, W. E., Varelas, X., Kukuruzinska, M. A., & Monti, S. (2023) · Human Genomics · doi:10.1186/s40246-023-00519-y · Cited by 33 · see citing works
“For instance, Fusobacterium —a gram-negative bacterium significantly more abundant in PML and OSCC than in control in our series (Additional file 1: Figure S5C and Additional file 3: Table S2)—has been shown to be abundant in patients diagnosed with oral cancer [27, 31].”
BackgroundResultSelf-citationMuñoz, C., Vidal, M., Rojas, T., Ferrada, L., Zuñiga, F. A., Vera, A. A., Sanhueza, S. A., Quiroga, R. A., Cabrera, C., Antilef, B., et al. (2025) · International Journal of Oral Science · doi:10.1038/s41368-024-00326-8 · Cited by 32 · see citing works
“Through the advent of high-throughput, next-generation sequencing (NGS), several studies have assessed to bacterial pro fi les associated with OSCC, detecting a group of periodontitis-related species enriched on tumoral tissues compared to controls samples 16 – 18 .”
Burcher, K. M., Burcher, J. T., Inscore, L., Bloomer, C. H., Furdui, C. M., & Porosnicu, M. (2022) · Cancers · doi:10.3390/cancers14174116 · Cited by 32 · see citing works
Liao, K., Wen, J., Liu, Z., Zhang, B., Zhang, X., Fu, Y., Zhang, W., Hu, H., Ai, K., Zhu, W., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102820 · Cited by 33 · see citing works
Bacteriome and mycobiome dysbiosis in oral mucosal dysplasia and oral cancer
Belibasakis, G. N., Seneviratne, C. J., Jayasinghe, R. D., Vo, P. T., Bostancı, N., & Choi, Y. (2024) · Periodontology 2000 · doi:10.1111/prd.12558 · Cited by 30 · see citing works
Self-citationAlterations of the Oral Microbiota Profiles in Chinese Patient With Oral Cancer
Li, Z., Chen, G., Wang, P., Sun, M., Zhao, J., Li, A., & Sun, Q. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.780067 · Cited by 30 · see citing works
Constantin, M., Chifiriuc, M. C., Mihăescu, G., Vrâncianu, C. O., Dobre, E.-G., Cristian, R.-E., Bleoţu, C., Bertesteanu, S. V., Grigore, R., Şerban, B., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1273516 · Cited by 29 · see citing works
“The presence of P. gingivalis in the oral cavity tend to be associated with higher mortality rates (61, 72, 73).”
BackgroundMicrobiomes, Their Function, and Cancer: How Metatranscriptomics Can Close the Knowledge Gap
Aitmanaitė, L., Širmonaitis, K., & Russo, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813786 · Cited by 26 · see citing works
“For example, shotgun metagenomics suggests that there are three main families of pathways that bacteria take advantage of in order to thrive in a tumour environment: oxidative stress, small molecule transport, and malfunctioning DNA repair [47,51,60,67,70,73,74,77,105,106].”
BackgroundInfluentialPotential role of epithelial–mesenchymal transition induced by periodontal pathogens in oral cancer
Ma, Y., Yu, Y., Yin, Y., Wang, L., Yang, H., Luo, S., Zheng, Q., Pan, Y., & Zhang, D. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18064 · Cited by 26 · see citing works
“30 Noticeably, the results of different studies are not completely consistent.”
Zhou, W., Zuomin, L., Wu, Z., Suyama, T., & Zhang, W. (2021) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.11105 · Cited by 26 · see citing works
Li, R., Hou, M., Yu, L., Luo, W., Liu, R., & Wang, H. (2023) · British Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.bjoms.2023.05.004 · Cited by 25 · see citing works
Radaic, A., Shamir, E. R., Jones, K., Villa, A., Garud, N. R., Tward, A. D., Kamarajan, P., & Kapila, Y. L. (2023) · Microorganisms · doi:10.3390/microorganisms11092250 · Cited by 24 · see citing works
Oral microbiome and oral cancer – The probable nexus
Deo, P. N., & Deshmukh, R. S. (2020) · Journal of Oral and Maxillofacial Pathology · doi:10.4103/jomfp.jomfp_20_20 · Cited by 23 · see citing works
“for functional characterization of complex microbial communities.[54]”
Spirito, F. D., Palo, M. P. D., Folliero, V., Cannatà, D., Franci, G., Martina, S., & Amato, M. (2023) · Cancers · doi:10.3390/cancers15235540 · Cited by 23 · see citing works
Heterogeneous lineage-specific arginine deiminase expression within dental microbiome species
Mann, A. E., Chakraborty, B., O’Connell, L. M., Nascimento, M. M., Burne, R. A., & Richards, V. P. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.01445-23 · Cited by 22 · see citing works
“We chose this isolation kit as it is designed to efficiently isolate small RNAs ( 200 nt), as well as total RNA, which play a crucial role in regulating bacterial global gene expression and are routinely used for microbiome studies (74–76).”
MethodChiscuzzu, F., Crescio, C., Varrucciu, S., Rizzo, D., Sali, M., Delogu, G., & Bussu, F. (2025) · Cancers · doi:10.3390/cancers17020171 · Cited by 22 · see citing works
“In 2018, Yost et al. carried out a meta-transcriptome analysis to profile mRNA expression in the oral microbiome in OSCC [68].”
Dysbiosis of Oral Microbiome: A Key Player in Oral Carcinogenesis? A Critical Review
Devaraja, K., & Aggarwal, S. (2025) · Biomedicines · doi:10.3390/biomedicines13020448 · Cited by 24 · see citing works
“…collected, the collection procedure (rinse, passive wash, swab, scrapping or biopsy) the pre-collection steps (use of oral washes, type of reagent used), and the selection of controls (normal healthy controls or contralateral normal mucosal lesions from cancer patients) [89,96,121,122,159].”
Arthur, R. A., Bezerra, R. D. S., Ximenez, J. P. B., Merlin, B. L., Morraye, R. D. A., Neto, J. V., Fava, N. D. M. N., Figueiredo, D. L. A., de Biagi, C. A. O., Summer Course 2020 group, et al. (2021) · Brazilian Journal of Microbiology · doi:10.1007/s42770-021-00491-6 · Cited by 21 · see citing works
“hanced pattern for iron transport in microbiomes associated with OSCC [78].”
BackgroundSantacroce, L., Muzio, E. L., Bottalico, L., Spirito, F., Charitos, I. A., Passarelli, P. C., & Jirillo, E. (2022) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530322666220629101357 · Cited by 21 · see citing works
Baraniya, D., Chitrala, K. N., & Al-Hebshi, N. N. (2022) · Journal of Oral Microbiology · doi:10.1080/20002297.2022.2073866 · Cited by 21 · see citing works
The Microbiome’s Influence on Head and Neck Cancers
Dorobisz, K., Dorobisz, T. A., & Zatoński, T. (2023) · Current Oncology Reports · doi:10.1007/s11912-022-01352-7 · Cited by 21 · see citing works
Microbial community alteration in tongue squamous cell carcinoma
Ye, P., Liu, Y., Cai, Y.-J., Yang, H., Xu, H., & Lu, Z.-Y. (2021) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-021-11593-4 · Cited by 18 · see citing works
Jain, V. K., Baraniya, D., El-Hadedy, D. E., Chen, T., Slifker, M. J., Alakwaa, F., Cai, K. Q., Chitrala, K. N., Fundakowski, C., & Al-Hebshi, N. N. (2023) · Cancer Research Communications · doi:10.1158/2767-9764.crc-22-0349 · Cited by 18 · see citing works
Dumitrescu, R., Bolchis, V., Fratila, A. D., Jumanca, D. E., Buzatu, B. L. R., Sava-Roşianu, R., Alexa, V. T., Găluşcan, A., & Bălean, O. (2025) · Microorganisms · doi:10.3390/microorganisms13020373 · Cited by 18 · see citing works
Khatoon, E., Hegde, M., Kumar, A., Daimary, U. D., Sethi, G., Bishayee, A., & Kunnumakkara, A. B. (2022) · Archives of Pharmacal Research · doi:10.1007/s12272-022-01398-y · Cited by 17 · see citing works
Association between oral microflora and gastrointestinal tumors (Review)
Li, X., Zhu, S., Zhang, T., & Chen, X. (2021) · Oncology Reports · doi:10.3892/or.2021.8111 · Cited by 17 · see citing works
“This is consistent with the conclusion of Yost et al (55), which indicated that Fusobacteria contained a significantly higher number of transcripts in patients with cancer than in healthy controls at tumor sites and tumor‑adjacent sites.”
Diwan, P., Nirwan, M., Bahuguna, M., Kumari, S. P., Wahlang, J., & Gupta, R. K. (2023) · Pathogens · doi:10.3390/pathogens12080996 · Cited by 18 · see citing works
Standardized studies of the oral microbiome: From technology‐driven to hypothesis‐driven
Gao, C., Li, X., Zhao, X., Yang, P., Wang, X., Chen, X., Chen, N., & Chen, F. (2022) · iMeta · doi:10.1002/imt2.19 · Cited by 15 · see citing works
Multi-omics analysis of fecal samples in colorectal cancer Egyptians patients: a pilot study
Khattab, R. H., Abo-Hammam, R. H., Salah, M., Hanora, A., Shabayek, S., & Zakeer, S. (2023) · BMC Microbiology · doi:10.1186/s12866-023-02991-x · Cited by 15 · see citing works
“Yost et al., 2018 reported that Dialister was more active in the tumor sites [48].”
BackgroundCrowley, C., Selvaraj, A., Hariharan, A., Healy, C. M., & Moran, G. P. (2024) · Microbial Genomics · doi:10.1099/mgen.0.001217 · Cited by 15 · see citing works
“The virulence landscape at oral tumour sites has also been investigated and it has been found, using meta-transcriptomic analysis, that pathways including iron acquisition, oxidative stress response and peptidase activity were increased at OSCC sites [20].”
Insights into the oral microbiota in human systemic cancers
Su, L., Yang, R., Sheng, Y., Ullah, S., Zhao, Y., Shunjiayi, H., Zhao, Z., & Wang, Q. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1369834 · Cited by 15 · see citing works
Zanetta, P., Squarzanti, D. F., Sorrentino, R., Rolla, R., Valletti, P. A., Garzaro, M., Dell’Era, V., Amoruso, A., & Azzimonti, B. (2021) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2021.1872487 · Cited by 15 · see citing works
He, B., Cao, Y., Zhuang, Z., Deng, Q., Qiu, Y., Pan, L., Zheng, X., Shi, B., Lin, L., & Chen, F. (2024) · Head & Neck · doi:10.1002/hed.27795 · Cited by 14 · see citing works
“32 However, some different genera found in this study did not fully overlap with those found in the United States, 33 Australia, 34 Japan, 35 or Sri Lanka, 29 such as Fusobacterium and Porphyromonas were also reported to be more abundant in the oral cancer group.”
ResultAgurto, M. I. G., Valenzuela, N. O., Canedo-Marroquín, G., Espinoza, D., & Tortora, S. C. (2024) · Cancers · doi:10.3390/cancers16203545 · Cited by 16 · see citing works
“Additionally, F. nucleatum boosts the production of haemolysins and adhesins and strengthens its iron transport system to support DNA synthesis and cellular respiration, thereby promoting microbial survival and proliferation within the tumour environment [101].”
BackgroundDóra, D., Kiraly, P., Somodi, C., Ligeti, B., Dulka, E., Gálffy, G., & Lohinai, Z. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05835-y · Cited by 14 · see citing works
“In addition, it was reported in patients with oral squamous cell carcinoma (OSCC) evaluated by MTR analysis, that an increase in peptidase activity, oxidative stress, and iron acquisition is overrepresented in tumor samples compared to healthy tissues [19].”
Araújo, L. L., Lourenço, T. G. B., & Colombo, A. P. V. (2023) · Journal of Applied Oral Science · doi:10.1590/1678-7757-2022-0359 · Cited by 14 · see citing works
Starska, K. (2025) · Cancers · doi:10.3390/cancers17213478 · Cited by 13 · see citing works
“Yost et al. [118] assessed the mRNA expression profile across the entire oral microbiome in OSCC with the aim of identifying specific molecular and metabolic functions associated with this disease.”
Selvaraj, A., McManus, G., Healy, C. M., & Moran, G. P. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1417946 · Cited by 13 · see citing works
Li, X., Jia, Y., Li, Y., Hei, H., Zhang, S., & Qin, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1582166 · Cited by 12 · see citing works
Ahmad, S., Jayamanne, D. T., Bergamin, S., Lawless, A. K., Guminski, A. D., Lee, A. V., Yuile, A., Wheeler, H., Eade, T., Back, M., et al. (2025) · Cancers · doi:10.3390/cancers17162667 · Cited by 18 · see citing works
“Fusobacterium , reported in 12 studies, was consistently enriched in patients, re-inforcing its role in epithelial invasion, immune modulation, and inflammation-driven tumor progression [44,45].”
Emerging implications of bacterial biofilm in cancer biology: Recent updates and major perspectives
Kushwaha, M., Nukala, V., Singh, A. K., Makharia, G. K., Mohan, A., Kumar, A., & Dalal, N. (2024) · Gut Microbes Reports · doi:10.1080/29933935.2024.2339270 · Cited by 12 · see citing works
Ramos, R. T., Sodré, C. S., Rodrigues, P. M. G., da Silva, A. M. P., Fuly, M. S., dos Santos, H. F., Gonçalves, L. S., Ferreira, D. D. C., & Ribeiro, M. G. (2020) · Oral and Maxillofacial Surgery · doi:10.1007/s10006-020-00873-4 · Cited by 12 · see citing works
Liu, X., Li, X., Xie, M., Guo, J.-Y., Zheng, X., Shi, S., Cui, Q., Zhang, D., Zhang, Z., & Wang, Z. (2023) · Journal of Stomatology Oral and Maxillofacial Surgery · doi:10.1016/j.jormas.2023.101736 · Cited by 12 · see citing works
The Function of the Oral Microbiome in Health and Disease
Frias‐Lopez, J., & Duran-Pinedo, A. E. (2020) · Springer eBooks · doi:10.1007/978-3-030-42990-4_10 · Cited by 12 · see citing works
Self-citationShitozawa, Y., Haro, K., Ogawa, M., Miyawaki, A., Saito, M., & Fukuda, K. (2022) · Scientific Reports · doi:10.1038/s41598-022-21031-8 · Cited by 11 · see citing works
Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer
Sajid, M., Sharma, P., Srivastava, S., Hariprasad, R., Singh, H., & Bharadwaj, M. (2023) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12534-z · Cited by 10 · see citing works
Reyes, M., Urra, H., & Peña‐Oyarzún, D. (2025) · Frontiers in Oral Health · doi:10.3389/froh.2025.1575721 · Cited by 10 · see citing works
Recent advancements in artificial intelligence‐powered cancer prediction from oral microbiome
Soghli, N., Khormali, A., Mahboubi, D., Peng, A., & Miguez, P. A. (2025) · Periodontology 2000 · doi:10.1111/prd.70000 · Cited by 9 · see citing works
Cell Junctions in Periodontal Health and Disease: An Insight
Puzhankara, L., Rajagopal, A., Kedlaya, M. N., Karmakar, S., Nayak, N., & Shanmugasundaram, S. (2023) · European Journal of Dentistry · doi:10.1055/s-0043-1775726 · Cited by 8 · see citing works
“This results in the inhibition of E-cadherin, upregulation of vimentin, β -catenin, and matrix metalloproteinases (MMPs) 54 with the transition from the epithelial to the mesenchymal phenotype affecting the integrity of the intercellular junctions of the epithelium.”
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Relationships between oral microbiome and head and neck squamous cell carcinoma: a systematic review
Guévelou, J. L., Larnaudie, A., Béné, M. C., Cocherie, T., Perazzi, M., El-Houat, Y., Kammerer, E., Bastit, V., & Pointreau, Y. (2025) · Oral Oncology · doi:10.1016/j.oraloncology.2025.107571 · Cited by 9 · see citing works
Guan, Z., Qi, H., & Feng, Q. (2025) · Open Research (University of Surrey) · doi:10.1002/viw.20240153 · Cited by 6 · see citing works
- Authors
- Yost, S., Stashenko, P., Choi, Y., Kukuruzinska, M., Genco, C. A., Salama, A., Weinberg, E. O., Kramer, C. D., & Frias-Lopez, J.
- Affiliations
- The Forsyth Institute (US)
- Boston University (US)
- Tufts University (US)
- ORCID
- Venue
- International Journal of Oral Science
- Published
- 2018-11-12
- Volume
- 10
- Issue
- 4
- Pages
- 32-32
- ISSN
- 1674-2818 (ISSN-L)
- 2049-3169
- PMC
- PMC6232154
- OpenAlex
- W2901836693
- Cited by
- 144
- References
- 73
- Citations by year
- 2026: 12 · 2025: 24 · 2024: 13 · 2023: 25 · 2022: 28 · 2021: 18 · 2020: 20 · 2019: 4
- FWCI
- 12.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Oral Science (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Boston University (Evans Center for Interdisciplinary Biomedical Research ARC)
- Forsyth Institute Pilot Grant
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- oral squamous cell carcinoma, oral microbiota, metatranscriptomics, Fusobacteria, virulence factors, microbial gene expression, iron transport, tryptophanase, superoxide dismutase, capsule biosynthesis, flagellar biosynthesis, chemotaxis, hemolysin, adhesins, reactive nitrogen intermediates
- MeSH terms
- Carcinoma, Squamous Cell, Humans, Mouth Neoplasms, Phylogeny, Pilot Projects, RNA, Messenger, Virulence, Virulence Factors, Metagenome, Transcriptome, Microbiota
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