Gut microbiota regulation of the intestinal mucus layer during postnatal development

本研究的目的是研究肠道驻留微生物群调节出生后肠道粘液层建立的潜在机制。粘液层在肠屏障功能中起关键作用，因为它保护上皮免受腔病原体和毒素的侵害。 粘液层位于粘膜和微生物群之间，微生物群是由数万亿微生物组成的复杂群落。肠道微生物群在出生后通过逐渐多样化的过程获得，在断奶后结束，当达到成人型组成时。这个过程与肠道屏障的建立，特别是粘液层的建立平行。虽然在成年人中，微生物群的组成调节上皮屏障相关基因的表达，但尚不清楚它是否在生命早期这样做。我们将在出生后不同时间从常规（具有“正常”微生物群）和无菌（无任何细菌）小鼠的肠道分离的上皮细胞中进行全局基因表达分析，以评估不断演变的肠道微生物群落对调节粘液层建立的基因及时适当表达的影响。鉴于粘液层组成的改变是几种胃肠疾病的特征，如炎症性肠病和粘膜炎，了解其建立的分子机制对理解这些病理以及设计新的疗法和治疗方法具有意义。此外，这项研究对制定膳食指南具有重要意义，通过营养方法改善人类健康，目标是维持肠道中健康的肠道微生物群落。

The purpose of this research is to investigate the underlying mechanisms by which the gut resident microbiota regulates the postnatal establishment of the intestinal mucus layer. The mucus layer plays a critical role in the intestinal barrier function since it protects the epithelium from luminal pathogens and toxins. The mucus layer is located between the mucosa and the microbiota, a complex community of trillions of microorganisms. The gut microbiota is acquired after birth through a gradual diversification process ending after weaning, when an adult-type composition is achieved. This process parallels the establishment of the gut barrier and in particular of the mucus layer. While in the adult the composition of the microbiota regulates the expression of epithelial barrier-related genes, it is not known if it does so in early life. We will perform a global gene expression analysis in epithelial cells isolated from the intestine of conventional (with a "normal" microbiota) and germ-free (without any bacteria) mice at different times after birth in order to assess the impact of the evolving gut microbial community on the timely appropriate expression of genes regulating the establishment of the mucus layer. Given that alteration of mucus layer composition characterizes several gastro-intestinal diseases, such as inflammatory bowel disease and mucositis, understanding the molecular mechanisms of its establishment has implications for the understanding of these pathologies as well as for the design of new therapies and treatments. Furthermore, this research has implications for the development of dietary guidelines to improve human health through nutritional approaches targeting the maintenance of a healthy gut microbial community in the intestine.