肠道菌群与雌激素交互作用调控牙槽骨炎性吸收的机制研究

The inflammatory bone resorptions occurred at alveolar bone are mainly attributed to periapical periodontitis (AP) and periodontitis, which are the major cause of toothache and tooth loss in elder population. In addition, AP and periodontitis are also correlated with systemic diseases such as cardiovascular diseases and diabetes, etc. Postmenopausal osteoporosis (PMO) not only compromises the hardness and microarchitecture of lone bone and spine, but also regulates the bone remodeling process of alveolar bone. Clinical treatment of AP and periodontitis-afflicting PMO women are more challenging. Recent studies have shown that gut microbiota plays an important role in the bone remodeling process, indicating its potential role in the management of PMO women afflicted with AP and periodontitis. Our preliminary study by establishing ovariectomy plus periodontitis rat models has demonstrated a correlation among estrogen-deficiency, gut microbiota and periodontitis. The current project aims to further investigate the mode of action and mechanisms by which gut microbiota interacts with estrogen during the development AP and periodontitis. Various probiotics will be screened by animal models, and optimal probiotics will be further validated in the treatment of AP and periodontitis patients. Results obtained from the proposed project will not only advance our knowledge on the role of gut microbiota in the development of oral diseases, but also provide promising paradigm and approach for the management of AP and periodontitis among PMO-afflicting population.

牙槽骨炎性吸收主要包括根尖周病、牙周病，是引起我国中老年人牙痛、失牙的最主要原因，与心血管疾病、糖尿病等具有共同危险因素。绝经后骨质疏松不但影响长骨和椎骨，对牙槽骨骨重建也有着重要影响。绝经后妇女罹患根尖周炎、牙周炎更不易控制。近期研究表明，肠道菌群参与调控人体骨代谢，有望成为绝经后妇女根尖周炎、牙周炎防治的新靶点。申请人前期通过构建卵巢切除+牙周炎大鼠模型，研究了雌激素缺乏、肠道微生态及牙周炎的相关性。本项目拟以根尖周炎、牙周炎为代表，进一步研究肠道菌群与雌激素交互作用在牙槽骨炎性吸收发生发展中的作用与机制，通过动物模型筛选对雌激素缺乏背景下根尖周炎、牙周炎治疗效果最佳的益生菌组合；通过临床研究，评估益生菌对绝经后妇女根尖周炎、牙周炎的防治作用。研究结果有利于深化对肠道菌群与口腔疾病交互作用机制的认识，也可为绝经后骨质疏松相关牙槽骨炎性吸收的防治提供新思路和途径。

绝经后骨质疏松不但影响长骨和椎骨，对牙槽骨重建也有着重要影响。绝经后妇女罹患根尖周炎、牙周炎更不易控制，为疾病防治提出了挑战。本项目从肠道微生物与骨免疫的角度，以根尖周炎和牙周炎为代表，系统研究了肠道菌群与雌激素交互作用在牙槽骨炎性吸收发生发展中的作用与机制。研究发现雌激素缺乏可导致肠道微生态失衡，肠道屏障渗透性增加，全身炎症反应导致骨髓Th17/Treg比例失衡，牙槽骨破骨活性增强，最终加重牙槽骨炎症性骨吸收；益生菌可有效改善雌激素缺乏导致的肠道微生态失衡，富集肠道产丁酸菌，改善肠道黏膜屏障功能，逆转骨髓Th17/Treg比例失衡，抑制破骨活性，缓解牙槽骨炎症性骨吸收。研究结果证实了益生菌在调控肠道微生态与骨免疫中的积极作用，有望为绝经后妇女炎症性骨吸收的防治提供新的思路和途径。