Radaic Allan, Shamir Eliah R, Jones Kyle, Villa Alessandro, Garud Nandita R, Tward Aaron D, Kamarajan Pachiyappan, Kapila Yvonne L
School of Dentistry, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
School of Dentistry, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA.
Microorganisms. 2023 Sep 7;11(9):2250. doi: 10.3390/microorganisms11092250.
Oral potentially malignant disorders (OPMDs) are a group of conditions that carry a risk of oral squamous cell carcinoma (OSCC) development. Recent studies indicate that periodontal disease-associated pathogenic bacteria may play a role in the transition from healthy mucosa to dysplasia and to OSCC. Yet, the microbial signatures associated with the transition from healthy mucosa to dysplasia have not been established. To characterize oral microbial signatures at these different sites, we performed a 16S sequencing analysis of both oral swab and formalin-fixed, paraffin-embedded tissue (FFPE) samples. We collected oral swabs from healthy mucosa (from healthy patients), histologically normal mucosa adjacent to dysplasia, and low-grade oral dysplasia. Additionally, FFPE samples from histologically normal mucosa adjacent to OSCC, plus low grade and high-grade oral dysplasia samples were also collected. The collected data demonstrate significant differences in the alpha and beta microbial diversities of different sites in oral mucosa, dysplasia, and OSCC, as well as increased dissimilarities within these sites. We found that the Proteobacteria phyla abundance increased, concurrent with a progressive decrease in the Firmicutes phyla abundance, as well as altered levels of , , , and when moving from healthy to diseased sites. Moreover, the swab sample analysis indicates that the oral microbiome may be altered in areas that are histologically normal, including in mucosa adjacent to dysplasia. Furthermore, trends in specific microbiome changes in oral swab samples preceded those in the tissues, signifying early detection opportunities for clinical diagnosis. In addition, we evaluated the gene expression profile of OSCC cells (HSC-3) infected with either , , , or and found that the three periodontopathogens enrich genetic processes related to cancer progression, including skin keratinization/cornification, while the commensal enriched processes related to RNA processing and adhesion. Finally, we reviewed the dysplasia microbiome literature and found a significant decrease in commensal bacteria, such as the genus, and a simultaneous increase in pathogenic bacteria, mainly phyla and genus. These findings suggest that features of the oral microbiome can serve as novel biomarkers for dysplasia and OSCC disease progression.
口腔潜在恶性疾病（OPMDs）是一组有发展为口腔鳞状细胞癌（OSCC）风险的病症。最近的研究表明，与牙周病相关的致病细菌可能在从健康黏膜向发育异常以及向OSCC的转变中起作用。然而，与从健康黏膜向发育异常转变相关的微生物特征尚未确定。为了表征这些不同部位的口腔微生物特征，我们对口腔拭子和福尔马林固定、石蜡包埋组织（FFPE）样本进行了16S测序分析。我们从健康黏膜（来自健康患者）、发育异常相邻的组织学正常黏膜以及低度口腔发育异常处采集了口腔拭子。此外，还收集了OSCC相邻的组织学正常黏膜的FFPE样本，以及低度和高度口腔发育异常样本。收集到的数据表明，口腔黏膜、发育异常和OSCC不同部位的α和β微生物多样性存在显著差异，并且这些部位内的差异也有所增加。我们发现，从健康部位到患病部位，变形菌门丰度增加，同时厚壁菌门丰度逐渐降低，以及、、和水平发生改变。此外，拭子样本分析表明，在组织学正常的区域，包括发育异常相邻的黏膜中，口腔微生物群可能会发生改变。此外，口腔拭子样本中特定微生物群变化的趋势先于组织中的变化，这意味着有临床诊断的早期检测机会。此外，我们评估了感染、、或的OSCC细胞（HSC-3）的基因表达谱，发现这三种牙周病原体丰富了与癌症进展相关的基因过程，包括皮肤角质化/角化，而共生菌丰富了与RNA加工和黏附相关的过程。最后，我们回顾了发育异常微生物群的文献，发现共生细菌，如属，显著减少，而主要是变形菌门和属的致病细菌同时增加。这些发现表明，口腔微生物群的特征可以作为发育异常和OSCC疾病进展的新型生物标志物。
