人体微生物组是人类“第二基因组”，但其起源、进化知之甚少。通过人为改变现代人的微生物群落结构来“模拟”微生物组的进化难度非常大，而古代样本为该研究提供了全新视角。牙结石是附在牙齿表明，主要是磷酸钙、口腔内微生物和食物残渣组成的钙化牙菌斑，记载着微生物群落和饮食结构信息。因其普遍存在、保存时间长、DNA含量高被认为是古DNA研究的最大资源。本项目通过对我国山东地区不同年代、地域的牙结石古DNA高通量测序分析，将首次还原我国古人口腔微生物群落状况，建立我国古人口腔微生物组数据库，并通过在时间和地理尺度的比较分析，系统揭示口腔微生物组进化；结合出土人骨的龋病、牙周病等情况和古人食谱信息（通过牙结石中食物残渣DNA解析），研究微生物群落结构变化与饮食、健康状况的关系，揭示人体微生物组进化的推动机制。重构部分口腔致病菌基因组并进行时间尺度的比较分析，为研究口腔相关疾病的成因、治疗和预防提供新参考

The human microbiome is the "second genome" of human beings, but its origin and evolution are poorly understood. It is very difficult to "simulate" the evolution of microbial group by artificially changing the microbial community structure of modern people, and the ancient samples provide a new perspective for the research. Dental calculus is a calcified plaque that is attached to the teeth and consists mainly of calcium phosphate, oral microbes and food debris, and records microbial community and dietary structure information. Because of its ubiquity, long-time preservation and high DNA content, it is considered to be the largest resource for ancient DNA research. Through high-throughput sequencing analysis of ancient dental calculus DNA in different ages and regions in Shandong Province, this project will restore the oral microbial community status of ancient Chinese people for the first time, and establish a database of oral microbiome in ancient China. Through the comparative analysis of time and geographical scales, the evolution of oral microbiome was systematically revealed, and the relationship between the change of microbial community structure and diet and health status was studied by combining the caries and periodontal diseases information of unearthed human bones and the dietary information of the ancients (through the DNA analysis of food residue in dental calculus), so as to reveal the driving mechanism of human microbiome evolution. Reconstructing oral pathogen genomes and conducting time-scale comparative analysis provides a new reference for studying the causes, treatment and prevention of oral related diseases.