Gut microbiota regulation of the intestinal mucus layer during postnatal development

本研究的目的是探讨肠道常驻微生物群调节出生后肠道黏液层建立的潜在机制。黏液层在肠道屏障功能中起着至关重要的作用，因为它保护上皮免受肠道病原体和毒素的侵害。黏液层位于粘膜和微生物群之间，微生物群是一个由数万亿微生物组成的复杂群落。肠道菌群在出生后通过逐渐多样化的过程获得，在断奶后达到成人类型的组成。这个过程与肠道屏障，特别是黏液层的建立是平行的。虽然在成人中，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早期生活中起作用。我们将对出生后不同时间从常规（具有“正常”微生物群）和无菌（没有任何细菌）小鼠肠道分离的上皮细胞进行全球基因表达分析，以评估肠道微生物群落的进化对调节黏液层建立的基因及时适当表达的影响。鉴于黏液层组成的改变是几种胃肠道疾病的特征，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重要意义。此外，该研究还有助于制定膳食指南，通过针对维持肠道中健康的肠道微生物群落的营养方法来改善人类健康。

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.