Microbiota post-transcriptional regulation of the intestinal barrier during postnatal life

本研究的目的是研究肠道内的微生物在出生后早期调节肠道屏障(肠道防御系统)的潜在机制。肠道中有数以万亿计的微生物，作为一个群落生活，其结构是在出生后逐渐获得的。这一过程与肠道屏障的建立平行，表明两者之间存在关系。事实上，已知肠道微生物通过影响基因表达来调节屏障。目前还不清楚这种情况是通过什么机制发生的，这就是本研究计划旨在做出贡献的地方。我们将采用全球方法，允许分析数百种不同的基因表达调控因子，称为microRNA(MiRNA)，以及数百种不同的微生物在小鼠出生后的不同时间点并行进行分析，我们将能够将两者联系起来。我们还将研究依赖于肠道驻留微生物群落组成和microRNA的基因表达变化如何影响肠道防御系统。为此，我们将使用常规(有“正常”微生物区系)和无菌(没有任何细菌)的小鼠，以直接确认肠道微生物群落对调节屏障的基因和蛋白质表达的影响。

The purpose of this research is to investigate the underlying mechanisms by which the microbes living within the gut regulate the intestinal barrier, which is the intestinal defense system, during early postnatal life. There are trillions of microbes in the gut, living as a community, the structure of which is gradually acquired after birth. This process parallels the establishment of the intestinal barrier, suggesting a relationship between the two. Indeed, it is known that gut microbes regulate the barrier by impacting gene expression. It is unknown through which mechanisms this happens, and this is where this research program aims at contributing. We will adopt global approaches that allow for the analysis of hundreds of different regulators of gene expression, called microRNA (miRNA), and hundreds of different microbes in parallel in mice at different time points after birth and we will be able to correlate the two. We will also investigate how gene expression changes that depend on the composition of the gut resident microbial community and on the microRNA, affect the gut defense system. To this end, we will use use conventional (with a "normal" microbiota) and germ-free (without any bacteria) mice in order to directly confirm the impact of the gut microbial community on the expression of genes and proteins regulating the barrier.