口腔微生物组结构与牙周病的关系研究

As one of the common oral diseases, periodontal disease is a chronic infectious disease which is also a risk factor that will lead to systematic diseases. As the initial factor of periodontal disease, microorganisms in dental plaque are indicated by researches that their pathogenic effect is not caused by specific bacteria but probably by several kinds of bacteria or even the result of the whole micro-ecosystem. Being limited by traditional microbial research methods, people’s understanding to oral micro-ecosystem still exists obvious deviation. Therefore, it’s of vital scientific significance to deeply study the exact relation between its structural features and function and periodontal disease from the entirety of oral microbiome. In this study, high-throughput sequencing, gas chromatography-mass spectroscopy(GC-MC), metagenome sequencing and fluorescence quantitative PCR techniques are adopted to study the features of oral microbiome under different clinical conditions and different time points of treatment in 3 groups of patients(i.e. periodontal health group, chronic periodontitis group and aggressive periodontitis group), and to primarily explore the related metabolism and core functional genes of the microbiome. Bioinformatics analysis is conducted to try to define and differentiate the core oral microbiome under different periodontal health conditions, i.e. “type”; and multi-omics results are linked to predict and validate the functional difference of core microbiome primarily. This study aims at revealing the effect of core oral microbiome and its metabolism on periodontal health and providing evidence for describing the pathogenesis of periodontal disease.

牙周病作为口腔常见病，是一种慢性感染性疾病，也是重要系统性疾病的危险因素。菌斑微生物作为牙周病的始动因子，研究表明，其致病作用并非是单一细菌，有可能是多种微生物，甚至整个微生态系统共同作用的结果。受限于传统微生物研究方法，人们对口腔微生态系的了解至今存在明显偏差，因此，从口腔微生物组的整体，深入研究其结构特点及其功能与牙周病的确切关系具有重要科学意义。本项目通过高通量测序、气-质联用、宏基因组测序及荧光定量PCR等技术，研究牙周健康、慢性牙周炎及侵袭性牙周炎三类人群的不同临床状态和干预治疗的不同时间节点相关口腔微生物组的特点，初步探索代谢组及核心微生物功能基因。通过生物信息学分析，试图定义不同牙周健康状态的口腔核心微生物组，区分“口腔型”；并将多个组学结果相关联，初步预测及验证核心微生物组的功能差异。旨在揭示口腔核心微生物组及其代谢对牙周健康的影响，为阐述牙周病的发病机制提供依据。

牙周炎的发生发展与口腔微生物菌群的活动是密切相关的，菌群的功能多是通过参与人体的代谢活动实现的。因此，认清口腔内微生物菌群的局部和整体结构特征及其代谢特点，对于揭示牙周炎发病机制有着重要意义。针对上述问题,本研究通过观察不同牙周健康状态下，口腔微生物组菌群结构及代谢物组成特点，探寻与牙周炎密切相关的菌属和代谢物，并初步探索菌群通过代谢参与牙周炎的致病机制。对牙周健康者、慢性牙周炎患者、侵袭性牙周炎患者三类人群，在牙周基础治疗前后进行全口牙周临床指标检查，采集唾液、龈下菌斑、龈沟液样本，运用16S rRNA基因高通量测序与气相色谱-质谱联用技术，分析治疗前后口腔微生物菌群结构和代谢物组成，并关联菌群与代谢物的关系。主要结论，一、牙周炎组与健康组口腔菌群结构存在显著差异，组间差异主要体现在低丰度稀有菌属，而两类牙周炎组的口腔菌群结构组间差异不显著。三组间唾液、龈沟液代谢物组成均具有显著差异。代谢物的变化对区分慢性牙周炎和侵袭性牙周炎可能具有一定的提示作用；二、两类牙周炎组的口腔菌群结构和龈沟液代谢物组成与牙周基础治疗后临床指标的改善和变化情况较为一致，而唾液代谢组不完全一致；三、牙周炎组基础治疗前与健康组比较，存在差异的菌属、代谢物，在基础治疗后，仍与健康组存在差异的，应进一步研究其在牙周炎发生发展中可能的作用。