ABSTRACT

Objective: While some oral carcinomas appear to arise de novo, others develop within long-standing conditions of the oral cavity that have malignant potential, now known as oral potentially malignant disorders (OPMDs). The oral bacteriome associated with OPMD has been studied to a lesser extent than that associated with oral cancer. To characterize the association in detail we compared the bacteriome in whole mouth fluid (WMF) in patients with oral leukoplakia, oral cancer and healthy controls.

Methods: WMF bacteriome from 20 leukoplakia patients, 31 patients with oral cancer and 23 healthy controls were profiled using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and taxonomical classification was performed using the phylogenetic placement method. Sparse Partial Least Squares Regression Discriminant Analysis model was used to identify bacterial taxa that best discriminate the studied groups.

Results: We found considerable overlap between the WMF bacteriome of leukoplakia and oral cancer while a clearer separation between healthy controls and the former two disorders was observed. Specifically, the separation was attributed to 14 taxa belonging to the genera Megaspheara, unclassified enterobacteria, Prevotella, Porphyromonas, Rothia and Salmonella, Streptococcus, and Fusobacterium. The most discriminative bacterial genera between leukoplakia and oral cancer were Megasphaera, unclassified Enterobacteriae, Salmonella and Prevotella.

Conclusion: Oral bacteria may play a role in the early stages of oral carcinogenesis as a dysbiotic bacteriome is associated with oral leukoplakia and this resembles that of oral cancer more than healthy controls. Our findings may have implications for developing oral cancer prevention strategies targeting early microbial drivers of oral carcinogenesis.

摘要

目的：虽然有些口腔癌似乎是从新出现的，但另一些则在长期存在的具有恶性潜能的口腔疾病中发展，现在称为口腔潜在恶性疾病（OPMD）。与OPMD相关的口腔细菌组的研究程度小于与口腔癌相关的口腔细菌组。为了详细描述这种关联，我们比较了口腔白斑，口腔癌和健康对照患者的全口液（WMF）中的细菌群。

方法：使用Illumina MiSeq平台对来自20名白斑患者，31名口腔癌患者和23名健康对照的WMF细菌进行分析。使用DADA2处理测序读取，并使用系统发育放置方法进行分类。稀疏偏最小二乘回归判别分析模型用于识别最能区分研究组的细菌类群。

结果：我们发现白斑的WMF细菌群与口腔癌有相当大的重叠，而健康对照与前两种疾病之间的分离更加清晰。具体地，该分离归因于属于大食角藻属，未分类的肠杆菌属，普氏杆菌，卟啉单胞菌，Rothia和沙门氏菌，链球菌和梭菌属的14个类群。白斑和口腔癌之间最有区别的细菌属是巨噬细胞，未分类的肠杆菌，沙门氏菌和普氏杆菌。

结论：口腔细菌可能在口腔癌发生的早期阶段发挥作用，因为不良细菌菌群与口腔白斑相关，并且比口腔癌更像口腔癌。我们的发现可能对制定针对口腔癌发生的早期微生物驱动因素的口腔癌预防策略具有影响。