Oral Microbial Changes in Oral Squamous Cell Carcinoma: Focus on Treponema denticola, Lactobacillus casei, and Candida albicans

<i>Background and Objectives:</i> 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. <i>Materials and Methods:</i> Twelve participants (8 females and 4 males; mean age, 54.33 ± 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 <i>Candida albicans</i>. <i>Results:</i> The analysis revealed significant differences for certain microorganisms, namely, <i>Treponema denticola</i> (<i>T. denticola</i>), <i>Lactobacillus casei</i> (<i>L. casei</i>), and <i>Candida albicans</i>. <i>T. denticola</i> was most abundant in the OSCC group (5,358,692.95 ± 3,540,767.33), compared to the stomatitis (123,355.54 ± 197,490.86) and healthy control (9999.21 ± 11,998.40) groups. <i>L. casei</i> was undetectable in the healthy control group but was significantly more abundant in the stomatitis group (1653.94 ± 2981.98) and even higher in the OSCC group (21,336.95 ± 9258.79) (<i>p</i> = 0.001). A similar trend was observed for <i>C. albicans</i>, with DNA copy numbers rising from the healthy control (464.29 ± 716.76) to the stomatitis (1861.30 ± 1206.15) to the OSCC group (9347.98 ± 5128.54) (<i>p</i> = 0.006). The amount of <i>T. denticola</i> was positively correlated with <i>L. casei</i> (r = 0.890, <i>p</i> < 0.001) and <i>C. albicans</i> (r = 0.724, <i>p</i> = 0.008). <i>L. casei</i>'s DNA copy number was strongly correlated with <i>C. albicans</i> (r = 0.931, <i>p</i> < 0.001). These three oral microbes exhibited strong positive correlations with each other and had various direct or indirect relationships with other species. <i>Conclusions:</i> In the OSCC group, <i>T. denticola</i>, <i>L. casei</i>, and <i>C. albicans</i> exhibited strong positive correlations with one another, further emphasizing the need for a deeper understanding of the complex microbial interactions in the OSCC environment.