{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:44:00Z","timestamp":1791902640225,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Medical Device Development Fund grant","award":["KMDF_PR_20200901_0023, 9991006696"],"award-info":[{"award-number":["KMDF_PR_20200901_0023, 9991006696"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: In this study, we aimed to explore the oral bacteria and fungi that can help discern oral squamous cell carcinoma (OSCC) and investigate the correlations between multiple key pathogens. Materials and Methods: Twelve participants (8 females and 4 males; mean age, 54.33 \u00b1 20.65 years) were prospectively recruited into three groups: Group 1: healthy control, Group 2: patients with stomatitis, and Group 3: patients with OSCC, with 4 individuals in each group. Unstimulated whole saliva samples from these participants were analyzed using real-time PCR to assess the presence and abundance of 14 major oral bacterial species and Candida albicans. Results: The analysis revealed significant differences for certain microorganisms, namely, Treponema denticola (T. denticola), Lactobacillus casei (L. casei), and Candida albicans. T. denticola was most abundant in the OSCC group (5,358,692.95 \u00b1 3,540,767.33), compared to the stomatitis (123,355.54 \u00b1 197,490.86) and healthy control (9999.21 \u00b1 11,998.40) groups. L. casei was undetectable in the healthy control group but was significantly more abundant in the stomatitis group (1653.94 \u00b1 2981.98) and even higher in the OSCC group (21,336.95 \u00b1 9258.79) (p = 0.001). A similar trend was observed for C. albicans, with DNA copy numbers rising from the healthy control (464.29 \u00b1 716.76) to the stomatitis (1861.30 \u00b1 1206.15) to the OSCC group (9347.98 \u00b1 5128.54) (p = 0.006). The amount of T. denticola was positively correlated with L. casei (r = 0.890, p &lt; 0.001) and C. albicans (r = 0.724, p = 0.008). L. casei\u2019s DNA copy number was strongly correlated with C. albicans (r = 0.931, p &lt; 0.001). These three oral microbes exhibited strong positive correlations with each other and had various direct or indirect relationships with other species. Conclusions: In the OSCC group, T. denticola, L. casei, and C. albicans exhibited strong positive correlations with one another, further emphasizing the need for a deeper understanding of the complex microbial interactions in the OSCC environment.<\/jats:p>","DOI":"10.3390\/medicina60111753","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T07:51:29Z","timestamp":1729842689000},"page":"1753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Oral Microbial Changes in Oral Squamous Cell Carcinoma: Focus on Treponema denticola, Lactobacillus casei, and Candida albicans"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7323-0411","authenticated-orcid":false,"given":"Yeon-Hee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Orofacial Pain and Oral Medicine, Kyung Hee University Dental Hospital, #613 Hoegi-dong, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junho","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Youn","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Periodontal-Implant Clinical Research Institute, School of Dentistry, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cell.2016.01.013","article-title":"Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans","volume":"164","author":"Sender","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41392-023-01693-0","article-title":"Intratumoural microbiota: A new frontier in cancer development and therapy","volume":"9","author":"Cao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s13046-021-02128-w","article-title":"The role of the tumor microbe microenvironment in the tumor immune microenvironment: Bystander, activator, or inhibitor?","volume":"40","author":"Ma","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/prd.12393","article-title":"The oral microbiome: Role of key organisms and complex networks in oral health and disease","volume":"87","author":"Sedghi","year":"2021","journal-title":"Periodontol. 2000"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gao, F., Yu, B., Rao, B., Sun, Y., Yu, J., Wang, D., Cui, G., and Ren, Z. (2022). The effect of the intratumoral microbiome on tumor occurrence, progression, prognosis and treatment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1051987"},{"key":"ref_6","first-page":"178","article-title":"The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra\u2014A retrospective 10-year study","volume":"21","author":"Tandon","year":"2017","journal-title":"Contemp. Oncol. (Pozn.)"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1590\/1679-775720130317","article-title":"Oral squamous cell carcinoma: Clinicopathological features from 346 cases from a single oral pathology service during an 8-year period","volume":"21","author":"Pires","year":"2013","journal-title":"J. Appl. Oral. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.12688\/f1000research.22941.1","article-title":"Oral squamous cell carcinoma: Metastasis, potentially associated malignant disorders, etiology and recent advancements in diagnosis","volume":"9","author":"Bugshan","year":"2020","journal-title":"F1000Res"},{"key":"ref_9","unstructured":"(2024, June 01). Available online: https:\/\/www.nidcr.nih.gov\/research\/data-statistics\/oral-cancer\/survival-rates."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104925","DOI":"10.1016\/j.micinf.2021.104925","article-title":"Porphyromonas gingivalis in oral squamous cell carcinoma: A review","volume":"24","author":"Singh","year":"2022","journal-title":"Microbes Infect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1177\/00220345211067401","article-title":"Treponema denticola Promotes OSCC Development via the TGF-\u03b2 Signaling Pathway","volume":"101","author":"Peng","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vadovics, M., Ho, J., Igaz, N., Alf\u00f6ldi, R., Rakk, D., Veres, \u00c9., Sz\u00fccs, B., Horv\u00e1th, M., T\u00f3th, R., and Sz\u00fccs, A. (2021). Candida albicans Enhances the Progression of Oral Squamous Cell Carcinoma In Vitro and In Vivo. mBio, 13.","DOI":"10.1101\/2021.03.31.437836"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lee, Y.H., Chung, S.W., Auh, Q.S., Hong, S.J., Lee, Y.A., Jung, J., Lee, G.J., Park, H.J., Shin, S.I., and Hong, J.Y. (2021). Progress in Oral Microbiome Related to Oral and Systemic Diseases: An Update. Diagnostics, 11.","DOI":"10.20944\/preprints202106.0529.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.aay9189","article-title":"The human tumor microbiome is composed of tumor type-specific intracellular bacteria","volume":"368","author":"Nejman","year":"2020","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1016\/j.cell.2022.09.015","article-title":"A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors","volume":"185","author":"Dohlman","year":"2022","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10096-004-1100-1","article-title":"False-Positive Results and Contamination in Nucleic Acid Amplification Assays: Suggestions for a Prevent and Destroy Strategy","volume":"23","author":"Borst","year":"2004","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, Y.H., Kim, H., Heo, D.W., Ahn, I.S., and Park, H.K. (2023). Oral microbiome of the inner surface of face masks and whole saliva during the COVID-19 pandemic. Front. Oral. Health, 4.","DOI":"10.3389\/froh.2023.1178020"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lee, Y.H., Kim, H., Heo, D.W., Ahn, I.S., and Auh, Q.S. (2023). Volatile sulfide compounds and oral microorganisms on the inner surface of masks in individuals with halitosis during COVID-19 pandemic. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-29080-3"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mimet.2018.02.010","article-title":"A quest to find good primers for gene expression analysis of Candida albicans from clinical samples","volume":"147","author":"Alonso","year":"2018","journal-title":"J. Microbiol. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14476\/jomp.2022.47.1.10","article-title":"Composition and Diversity of Salivary Microbiome Affected by Sample Collection Method","volume":"47","author":"Lee","year":"2022","journal-title":"JOMP"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Strain, M.C., Lada, S.M., Luong, T., Rought, S.E., Gianella, S., Terry, V.H., Spina, C.A., Woelk, C.H., and Richman, D.D. (2013). Highly precise measurement of HIV DNA by droplet digital PCR. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055943"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ostheim, P., Tich\u00fd, A., Sirak, I., Davidkova, M., Stastna, M.M., Kultova, G., Paunesku, T., Woloschak, G., Majewski, M., and Port, M. (2020). Overcoming challenges in human saliva gene expression measurements. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67825-6"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1177\/0022034510363105","article-title":"Killing of Treponema denticola by mouse peritoneal macrophages","volume":"89","author":"Gaibani","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, Q., Shao, Z., Liu, K., Zhou, X., Wang, L., Jiang, E., Luo, T., and Shang, Z. (2021). Salivary Porphyromonas gingivalis predicts outcome in oral squamous cell carcinomas: A cohort study. BMC Oral. Health, 21.","DOI":"10.1186\/s12903-021-01580-6"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Meyle, J., and Groeger, S. (2024). Periodontal pathogens and cancer development. Periodontol. 2000, Epub ahead of print.","DOI":"10.1111\/prd.12590"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, T.J., Hao, Y.H., Tang, Y.L., and Liang, X.H. (2022). Periodontal Pathogens: A Crucial Link Between Periodontal Diseases and Oral Cancer. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.919633"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"van Dijk, M.C., Petersen, J.F., Raber-Durlacher, J.E., Epstein, J.B., and Laheij, A. (2024). Diversity and compositional differences in the oral microbiome of oral squamous cell carcinoma patients and healthy controls: A scoping review. Front. Oral. Health, 5.","DOI":"10.3389\/froh.2024.1366153"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sun, J., Tang, Q., Yu, S., Xie, M., Zheng, W., Chen, G., Yin, Y., Huang, X., Wo, K., and Lei, H. (2023). F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production. EBioMedicine, 88.","DOI":"10.1016\/j.ebiom.2023.104444"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1941710","DOI":"10.1080\/19490976.2021.1941710","article-title":"\"Driver-passenger\" bacteria and their metabolites in the pathogenesis of colorectal cancer","volume":"13","author":"Avril","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/ohn.211","article-title":"Microbial Changes Associated With Oral Cavity Cancer Progression","volume":"168","author":"Yan","year":"2023","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nrmicro2819","article-title":"A bacterial driver-passenger model for colorectal cancer: Beyond the usual suspects","volume":"10","author":"Tjalsma","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dempsey, E., and Corr, S.C. (2022). Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.840245"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sukmana, B.I., Saleh, R.O., Najim, M.A., Al-Ghamdi, H.S., Achmad, H., Al-Hamdani, M.M., Taher, A.A., Alsalamy, A., Khaledi, M., and Javadi, K. (2024). Oral microbiota and oral squamous cell carcinoma: A review of their relation and carcinogenic mechanisms. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1319777"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1574-695X.2010.00773.x","article-title":"Microbial diversity in saliva of oral squamous cell carcinoma","volume":"61","author":"Pushalkar","year":"2011","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Su, L., Yang, R., Sheng, Y., Ullah, S., Zhao, Y., Shunjiayi, H., Zhao, Z., and Wang, Q. (2024). Insights into the oral microbiota in human systemic cancers. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1369834"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"823902","DOI":"10.1155\/2012\/823902","article-title":"Reactive oxygen species and inhibitors of inflammatory enzymes, NADPH oxidase, and iNOS in experimental models of Parkinson\u2019s disease","volume":"2012","author":"Koppula","year":"2012","journal-title":"Mediators Inflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1128\/AEM.04272-13","article-title":"H(2)O(2) production in species of the Lactobacillus acidophilus group: A central role for a novel NADH-dependent flavin reductase","volume":"80","author":"Hertzberger","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sami, A., Elimairi, I., Stanton, C., Ross, R.P., and Ryan, C.A. (2020). The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome-Treatment Axis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218061"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Vila, T., Sultan, A.S., Montelongo-Jauregui, D., and Jabra-Rizk, M.A. (2020). Oral Candidiasis: A Disease of Opportunity. J. Fungi, 6.","DOI":"10.3390\/jof6010015"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"He, S., Chakraborty, R., and Ranganathan, S. (2023). Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021050"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sultan, A.S., Theofilou, V.I., Alfaifi, A., Montelongo-Jauregui, D., and Jabra-Rizk, M.A. (2022). Is Candida albicans an opportunistic oncogenic pathogen?. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010413"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"d\u2019Enfert, C., Kaune, A.K., Alaban, L.R., Chakraborty, S., Cole, N., Delavy, M., Kosmala, D., Marsaux, B., Fr\u00f3is-Martins, R., and Morelli, M. (2021). The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: Current knowledge and new perspectives. FEMS Microbiol. Rev., 45.","DOI":"10.1093\/femsre\/fuaa060"},{"key":"ref_43","first-page":"100090","article-title":"A review on association of fungi with the development and progression of carcinogenesis in the human body","volume":"3","author":"Lee","year":"2022","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yu, D., and Liu, Z. (2022). The research progress in the interaction between Candida albicans and cancers. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.988734"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wacleche, V.S., Landay, A., Routy, J.P., and Ancuta, P. (2017). The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and HIV-1 Pathogenesis. Viruses, 9.","DOI":"10.3390\/v9100303"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zhao, H., Chu, M., Huang, Z., Yang, X., Ran, S., Hu, B., Zhang, C., and Liang, J. (2017). Variations in oral microbiota associated with oral cancer. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11779-9"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sawant, S., Dugad, J., Parikh, D., Srinivasan, S., and Singh, H. (2021). Identification & correlation of bacterial diversity in oral cancer and long-term tobacco chewers- A case-control pilot study. J. Med. Microbiol., 70.","DOI":"10.1099\/jmm.0.001417"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1002\/mco2.221","article-title":"Human microbiomes in cancer development and therapy","volume":"4","author":"Xia","year":"2023","journal-title":"MedComm (2020)"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Widyastuti, Y., Febrisiantosa, A., and Tidona, F. (2021). Health-Promoting Properties of Lactobacilli in Fermented Dairy Products. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.673890"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hill, D., Sugrue, I., Tobin, C., Hill, C., Stanton, C., and Ross, R.P. (2018). The Lactobacillus casei Group: History and Health Related Applications. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02107"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/jre.12691","article-title":"Role of Porphyromonas gingivalis in oral squamous cell carcinoma development: A systematic review","volume":"55","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1177\/0022034520907341","article-title":"From Beyond the Pale to the Pale Riders: The Emerging Association of Bacteria with Oral Cancer","volume":"99","author":"Fitzsimonds","year":"2020","journal-title":"J. Dent. Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:20:16Z","timestamp":1760113216000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,25]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["medicina60111753"],"URL":"https:\/\/doi.org\/10.3390\/medicina60111753","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,25]]}}}