婴幼儿口腔与肠道微生物群生物相关性研究

Abstract: The Human Microbiome Project (HMP) has underscored the ecological importance of both oral and gut microbiome, which is one of the major determinants of human growth, development, health and diseases. Delineation of the colonization and succession of oral and gut microbiome, as well as the microbial correlations and interactions between these two niches will advance the ecological management of both oral and systemic diseases. Our previous study by profiling the microbial composition of volunteers of varied age/dentition phases has revealed the temporal and spatial characteristics of oral microbiome. The current project is to perform a 3-year perspective cohort study, aiming to pinpoint key factors that affect the colonization, development and maturation of both oral and gut microbiome. Extensive bioinformatics along with in vitro and animal studies will be further employed to identify community correlations and microbial interactions between the oral cavity and gut. Data obtained from the current study will not only advance our knowledge on the development of human microbiome, particularly oral and gut microbiome, but will also provide potential ecological approach to a better management of both oral and systemic diseases that have microbial involvement.

口腔与肠道微生物群落结构和功能的动态变化与人体生长、发育、健康、疾病密切相关。解析婴幼儿口腔与肠道菌群定植与演替生态规律，探索口腔与肠道菌群的生物遗传相关性，有望为口腔与全身疾病的防治提供新途径。申请人前期通过分析不同年龄/牙列阶段人群口腔微生物群落结构，系统解析了口腔微生物组在时间（年龄/牙列阶段）和空间（口腔位点）维度的生态定植与演替规律。本项目拟进一步以家庭为单位，纵向追踪婴幼儿（出生至3岁）的生理、生活事件以及口腔与全身健康状况，借助微生物群落高通量测序分析平台与体外、动物研究模型，系统研究口腔、肠道菌群结构/功能的动态变化规律及关键影响因素，揭示口腔微生物群落在定植及演替过程中与肠道微生物的交互作用。研究结果不但有利于深化对“人类第二基因组”——微生物组发育、成熟机制的认识，更有助于从微生态平衡的角度，为口腔及全身相关疾病的防治提供理论依据。

口腔与肠道微生物群落结构和功能的动态变化与人体生长、发育、健康、疾病密切相关。解析婴幼儿口腔与肠道菌群定植与演替生态规律，探索口腔与肠道菌群相关性，有望为口腔与全身疾病的防治提供新途径。本项目通过建立以家庭为单位的新生儿队列，对13个家庭的14个婴幼儿、父母及其他主要照护者的临床资料、重要生活事件，以及口腔与肠道微生物样本进行了动态采集与测序分析，深入研究了婴幼儿从出生到3岁的口腔及肠道微生物群定植及演替规律及关键影响因素，并对口腔与肠道微生物群落组成相关性进行了初步分析。研究发现，婴幼儿口腔和肠道菌群的定植和演替受到外界因素的影响，其组成和群落特性随婴幼儿年龄和生理生活事件的变化而变化。早期婴幼儿口腔和肠道的群落特征较为独特，并受到的出生方式和喂养方式的影响，而随着年龄的增长和外界因素的影响，逐渐向成年人相关位点的菌群趋近。口腔与肠道菌群可能存在位点间的移位定植，表现为：1）部分菌属先出现于口腔，其丰度在短期内明显减少，而肠道内丰度明显增加，主要包括双歧杆菌属、肠球菌属、拟杆菌属，Cutibacterium，乌拉尔菌属；2）葡萄球菌属和罗氏菌属早期即在唾液样本中表现出较高的丰度，但在早期的粪便样本中短暂出现并迅速消减；3）韦荣球菌属和孪生球菌属则先出现于粪便样本，继而才在唾液样本中被检出。研究结果不但有利于深化对口腔与肠道微生物组发育、成熟机制的认识，更有助于从微生态平衡的角度，为口腔及全身相关疾病的防治提供理论依据。