新生儿肠道菌群的演替过程与健康有着密切关系。新生儿肠道菌群演替过程的紊乱与多种代谢性疾病相关。目前对新生儿肠道菌群演替过程的研究多基于相关性分析，急需在机制层面深入探讨影响新生儿肠道菌群演替过程的因素。我们前期已经利用从同一婴幼儿粪便中分离的68株肠道菌株在无菌小鼠中建立了模拟新生儿肠道菌群演替过程的体系，并利用这一体系发现不同时期肠道菌群的相互竞争关系和营养代谢能力的区别。本项目将在前期基础上，结合细菌遗传学领域的先进手段(Tn-seq)，对所分离的代表新生儿不同发育时期的关键肠道菌株构建全基因组转座子突变库，并利用无菌小鼠模型，结合前期通过RNASeq, 代谢组学方法获得的数据，研究肠道菌群糖类，氨基酸和B族维他命代谢通路对新生儿肠道菌群演替过程的调控作用，并针对特定代谢通路设计靶向干预策略，为改善新生儿营养与代谢提供新方法。

The microbial succession process in the infant gut plays important roles in health. Aberrant succession has been linked to multiple metabolic diseases. Current studies of the infant gut microbiota succession process are mostly based on correlation analysis. Mechanistic studies of the factors that regulate the microbial succession process is needed. We have modeled the microbial succession process in gnotobiotic mice using 68 bacterial strains isolated from the feces of a single infant. We found that microbial communities from different developmental stages compete to colonize the mammalian gut and they have different metabolic capacities. To further dissect the genomic and metabolic underpinnings of this process, we will combine Tn-seq (transposon sequencing) and gnotobiotic mouse models to characterize the roles of key metabolic pathways (carbohydrate, amino acid and B vitamin pathways) that regulate microbial succession and design new ways to improve infant nutrition and metabolism through the modulation of the gut microbiota.