Intini Rossella, Balsells Sol, Bagan Leticia, Fortuna Giulio, Sroussi Herve, Bagan Jose
Oral Medicine Unit, Stomatology Department, Valencia University, Valencia, Spain.
Statistical Advising Service, Fundació de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain.
Front Oral Health. 2025 May 14;6:1600090. doi: 10.3389/froh.2025.1600090. eCollection 2025.
Oral potentially malignant disorders (OPMDs), including conventional leukoplakia (OL) and proliferative verrucous leukoplakia (PVL), have distinct risks of progression to oral squamous cell carcinoma (OSCC). A role of the oral microbiome in this transformation is increasingly recognized, but its contribution remains unclear.
This study aimed to analyze and compare the oral microbiota in patients with OL, PVL, and OSCC using 16S rRNA gene sequencing of saliva samples to identify microbial signatures associated with disease progression and to uncover potential biomarkers that would justify an aggressive treatment of OPMDs.
Sixty-six subjects with OPMDs were enrolled, comprising OL ( = 10), PVL ( = 28), and OSCC ( = 28). Saliva samples were collected, and DNA was extracted. The V3-V4 regions of the 16S rRNA gene were sequenced using the Illumina MiSeq platform. Bioinformatic analyses, including diversity assessments and taxonomic classification with the SILVA v138 database, were performed using QIIME2. Alpha diversity was evaluated with Chao1, Shannon, and Simpson indices, while beta diversity was assessed using Bray-Curtis and Jaccard distances.
PVL exhibited the highest species richness, followed by OL, with OSCC showing the lowest diversity. While alpha diversity differences among the groups were not statistically significant ( > 0.05), beta diversity revealed distinct microbial community structures between OL and both PVL and OSCC ( < 0.05), but not between PVL and OSCC. At the phylum level, predominated across all groups, with significantly higher levels in OL ( = 0.002).
Distinct microbial patterns differentiate OL from PVL and OSCC, with OL being different from PVL and OSCC, suggesting progressive microbial dysbiosis in malignant transformation. These findings support the potential of oral microbiome profiling as a non-invasive diagnostic and prognostic tool in oral oncology and highlight the need for longitudinal studies to establish causal relationships.
口腔潜在恶性疾病（OPMDs），包括传统型白斑（OL）和增殖性疣状白斑（PVL），进展为口腔鳞状细胞癌（OSCC）的风险各不相同。口腔微生物群在这种转变中的作用日益受到认可，但其贡献仍不明确。
本研究旨在通过对唾液样本进行16S rRNA基因测序，分析和比较OL、PVL和OSCC患者的口腔微生物群，以识别与疾病进展相关的微生物特征，并发现能够证明对OPMDs进行积极治疗合理的潜在生物标志物。
纳入66例患有OPMDs的受试者，包括OL患者（n = 10）、PVL患者（n = 28）和OSCC患者（n = 28）。收集唾液样本并提取DNA。使用Illumina MiSeq平台对16S rRNA基因的V3-V4区域进行测序。使用QIIME2进行生物信息学分析，包括多样性评估和使用SILVA v138数据库进行分类学分类。使用Chao1、Shannon和Simpson指数评估α多样性，使用Bray-Curtis和Jaccard距离评估β多样性。
PVL表现出最高的物种丰富度，其次是OL，OSCC的多样性最低。虽然各组之间的α多样性差异无统计学意义（P > 0.05），但β多样性显示OL与PVL和OSCC之间存在明显不同的微生物群落结构（P < 0.05），但PVL和OSCC之间不存在。在门水平上，所有组中厚壁菌门占主导，OL中的厚壁菌门水平显著更高（P = 0.002）。
不同的微生物模式将OL与PVL和OSCC区分开来，OL与PVL和OSCC不同，提示在恶性转化过程中存在渐进性的微生物失调。这些发现支持口腔微生物群分析作为口腔肿瘤学中非侵入性诊断和预后工具的潜力，并强调需要进行纵向研究以建立因果关系。
