地方性氟中毒是我国重点防控疾病之一，肠道微生态及其引起的代谢组学改变可能是影响氟中毒流行程度的关键所在。课题组在前期探索性研究的基础上，以磷酸戊糖/糖醛酸途径为切入点，探讨不同肠道微生态及其介导的代谢组学改变在儿童氟斑牙及骨代谢异常中的作用。研究在分析不同氟暴露水平下儿童氟斑牙流行特征及骨代谢相关生物标志变化的基础上，借助于Illumiina Hiseq宏基因组测序技术平台，以病例对照研究检测分析儿童肠道微生物群落结构及功能状态与氟斑牙的关系，阐明氟暴露和肠道微生态在氟斑牙发生中的作用。在此基础上，运用Thermo GC-MS靶向代谢组学技术，筛选病例组与对照组磷酸戊糖/糖醛酸代谢途径关键代谢产物的差异，探讨氟暴露-肠道微生态-磷酸戊糖/糖醛酸代谢组分变化-氟斑牙和骨代谢之间的关系，阐明氟与肠道微生态共同调节机体代谢在氟中毒发生发展中的作用，为氟中毒流行规律及发病机制的研究提供理论基础。

Endemic fluorosis is one of the important public issues in China. The intestinal microecology and its metabolomic changes may be the key factor for the prevalence of fluorosis. On the basis of our previous pilot study, the current study intends to explore the effects of intestinal microecology and its metabolomic changes on dental fluorosis and bone metabolism in children by the pentose phosphate/glucuronic acid pathway. Firstly, the epidemiological characteristics of dental fluorosis and the changes of bone metabolism-related biomarkers in children with different levels of fluoride exposure were investigated. Secondly, a case-control study will be conducted to analyze the structural and functional status of intestinal microbial communities in children using Illumina Hiseq technology platform, and the relationship between fluoride exposure, intestinal microecology and dental fluorosis will be clarified. Based on above results, the difference of key metabolites in pentose phosphate/glucuronic acid metabolic pathway between case group and control group will be screened by targeted metabolomics’ method using Thermo GC-MS technology. The association of fluoride exposure, intestinal microecology, changes of pentose phosphate/glucuronic acid metabolic components, dental fluorosis and bone metabolism will be discussed. It may provide a theoretical basis for the study of epidemic regularity and pathogenesis of fluorosis.