How do commensal bacteria protect against gut infection? (SCHULLER_F17DTP1)

人体内有数万亿的肠道细菌（微生物群），其中大部分位于结肠。大多数细菌是严格厌氧的，不耐受氧气。虽然人类宿主为细菌提供了营养丰富的环境，但微生物群增强了多糖的代谢并产生必需的维生素。此外，微生物群保护宿主免受肠道感染，并在组织稳态和免疫系统调节中具有有益作用。虽然食源性病原体如何干扰肠道功能已经得到了很好的证实，但微生物群如何抵消这些影响的潜在分子机制在很大程度上仍然未知。这主要是由于缺乏支持厌氧菌存活的实验肠道模型系统。在这里，我们将使用我们最近开发的垂直扩散室（VDC）系统来评估病原体-宿主-宿主相互作用的影响，该系统允许我们在厌氧环境中进行人肠上皮细胞与细菌的共孵育。本项目的目的是优化VDC培养模型，以支持肠道共生菌的最佳生长和粘附，确定肠道菌与上皮表面的相互作用，并研究肠道菌对肠致病性E.大肠杆菌诱导的上皮渗透性、离子吸收损失和炎症。

The human body is populated by trillions of commensal bacteria (microbiota), the majority of which reside in the colon. Most bacteria are strictly anaerobic and do not tolerate oxygen. While the human host provides the bacteria with a nutrient-rich environment, the microbiota enhances the metabolism of polysaccharides and produces essential vitamins. In addition, the microbiota protects the host against enteric infections and has a beneficial role in tissue homeostasis and modulation of the immune system. While it is well established how foodborne pathogens interfere with intestinal function, the underlying molecular mechanisms of how the microbiota counteracts these influences remain largely unknown. This is mainly due to a lack of experimental intestinal model systems supporting the survival of anaerobic bacteria.Here we will assess the impact of pathogen-commensal-host interactions using a Vertical Diffusion Chamber (VDC) system which we have recently developed to allow us to perform co-incubations of human intestinal epithelial cells with bacteria in an anaerobic environment. The aim of this project is to optimise the VDC culture model to support optimal growth and adhesion of gut symbionts, determine the interactions of commensals with the epithelial surface, and investigate the effect of gut commensals on enteropathogenic E. coli-induced epithelial permeability, loss of ion absorption and inflammation.