Modulation of the intestinal barrier by the intestinal microbiota - Role of dietetic factors and the mucosal immune system

肠道微生物群对肠道屏障的调节——饮食因素和粘膜免疫系统的作用

• 批准号: 237715737
• 负责人: Professor Dr. Stephan Bischoff
• 金额: --
• 依托单位: Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/237715737?language=en
• 关键词: Modulation; intestinal; barrier; microbiota; Role

The intestinal barrier is a complex functional entity consisting of mechanical components, but also immunological, neuronal and paracrine signals. On the one hand, it protects us against harmful components in the intestinal lumen, on the other, it allows absorption of fluids and nutrients required for survival. Moreover, it controls the intestinal microbiota, and in turn, the microbiota is one of the major regulators of the barrier function. Recently, data are cumulating that suggest a central role of the intestinal barrier for health and development of disease, the latter including both intestinal and extraintestinal diseases. Therefore, the interest in understanding this barrier in detail is now growing. In particular, we want to know how this barrier works, how we can assess barrier functions, and how we can support it. This is what is our project about.The major objective of our project is to study the complex interaction between diet, commensal bacteria and the host’s mucosa in the intestine in order to understand how the intestinal barrier is regulated under normal and inflammatory conditions. In particular, we aim to define molecular mechanisms how the intestinal microbiota and the intestinal mucosal immune system, either alone or together, affect the intestinal barrier and – vice versa – how the barrier may shape the intestinal microbiota and the intestinal mucosal immune system. In this context, the role of environmental factors such as dietary components known to modulate the barrier either directly or via alterations of the composition and function of the intestinal microbiota will be studied. In the first three years, all experiments will be performed in appropriate mouse models; afterwards the project will be extended to humans and human diseases.We expect new insights in dietetic, microbial and immunological factors modulating the intestinal barrier and therefore being of potential relevance for health and disease. From our approach, we also expect to define new strategies for future therapeutic interventions at the level of the intestinal barrier (e.g. dietary concepts, new probiotics, biologicals) with the potential to support barrier functions and thereby to prevent or treat diseases like IBD or intestinal infections. By doing this, we aim to increase our knowledge on how the intestinal barrier, the intestinal microbiota, and the intestinal immune system affect health and diseases.

肠屏障是一个复杂的功能实体，由机械部件组成，但也有免疫、神经元和旁分泌信号。一方面，它保护我们免受肠腔中有害成分的伤害，另一方面，它允许吸收生存所需的液体和营养。此外，它控制肠道微生物区系，反过来，微生物区系是屏障功能的主要调节因素之一。最近，越来越多的数据表明，肠道屏障对健康和疾病的发展起着核心作用，后者包括肠道和肠外疾病。因此，人们对详细了解这一障碍的兴趣正在增长。特别是，我们想知道这一障碍是如何运作的，我们如何评估障碍的功能，以及我们如何支持它。这就是我们的项目。我们项目的主要目标是研究饮食、共生菌和宿主肠道粘膜之间的复杂相互作用，以了解在正常和炎症条件下肠道屏障是如何调节的。特别是，我们的目标是确定肠道微生物区系和肠道粘膜免疫系统如何单独或共同影响肠屏障的分子机制，反之亦然--屏障如何塑造肠道微生物区系和肠粘膜免疫系统。在这方面，将研究环境因素的作用，如已知的直接或通过改变肠道微生物区系的组成和功能来调节屏障的饮食成分。在头三年，所有的实验都将在合适的小鼠模型中进行；之后，该项目将扩展到人类和人类疾病。我们希望在饮食、微生物和免疫因素调节肠道屏障方面有新的见解，从而对健康和疾病具有潜在的相关性。通过我们的方法，我们还希望为未来在肠道屏障水平上的治疗干预(例如饮食概念、新的益生菌、生物制品)定义新的战略，以支持屏障功能，从而预防或治疗IBD或肠道感染等疾病。通过这样做，我们的目标是增加我们对肠道屏障、肠道微生物区系和肠道免疫系统如何影响健康和疾病的知识。