Aging-associated modification of intestinal homeostasis and barrier function: Role of microbiota, iNOS and innate immunity

与衰老相关的肠道稳态和屏障功能的改变：微生物群、iNOS 和先天免疫的作用

• 批准号: 316103283
• 负责人: Professorin Dr. Ina Bergheim
• 金额: --
• 依托单位: Fachgebiet Tierernährung (460a)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316103283?language=en
• 关键词: Aging; associated; modification; intestinal; homeostasis

Results of several studies suggest that intestinal microbiota and barrier function may majorly impact health maintenance and longevity thereby also modulating healthy life-span. Furthermore, impairments of intestinal barrier function, changes in intestinal microbiota composition and alterations of the TH1/TH2 cell balance as well as redox status in the gut are discussed to be critical in the development of the low-grade inflammation frequently found in elderly. We recently found that old age in mice is associated with changes of intestinal microbiota composition and impairments of intestinal barrier function which went alongwith decreased expression levels of iNOS and proinflammatory mediators in the upper parts of the small intestine. However, the interaction between intestinal microbiota, barrier function, immune system and aging-associated degeneration and decline is only partially understood. Starting from this background, using mouse models the aim of the present research project is (1) to delineate at what age modifications of intestinal homeostasis and barrier function set in and if these changes are associated with alterations of intestinal microbiota composition and NO bioavailability as well as TH1 cells prevalence in small and large intestinal tissue, and (2) to determine the role of NO-synthesis through iNOS in aging-associated modifications of intestinal microbiota composition and barrier function. Herein, we will especially focus on the role of dietary composition and energy bioavailability as well as the identification of novel targeting strategies to prevent aging-associated alterations of intestinal microbiota composition and barrier function. We thereby also aim to add to the understanding of the fundamental principles of microbe-host interaction.

几项研究的结果表明，肠道菌群和屏障功能可能主要影响健康维持和寿命，从而调节健康的寿命。此外，讨论了肠道屏障功能的损害，肠道菌群组成的变化以及Th1/Th2细胞平衡的改变以及肠道中的氧化还原状态对于在老年人中经常发现的低度炎症的发展至关重要。我们最近发现，小鼠的老年与肠道菌群组成的变化以及肠道屏障功能的损害有关，这与小肠上部的iNOS和促炎介质的表达水平降低有关。然而，只有部分了解肠道菌群，屏障功能，免疫系统和衰老相关的变性和下降之间的相互作用。从这种背景开始，使用鼠标模型，本研究项目的目的是（1）在肠道稳态和屏障功能的何种年龄修饰和设置的屏障功能的变化以及这些变化是否与肠道微生物群的改变有关，也没有生物利用度的变化有关随着Th1细胞在大小肠道组织中的患病率，以及（2）确定通过iNOS在肠道菌群组成和屏障功能的衰老相关修饰中的NO合成作用。本文中，我们将特别关注饮食组成和能量生物利用度的作用，以及鉴定新的靶向策略，以防止肠道菌群组成和屏障功能的衰老相关变化。因此，我们还旨在增加对微生物 - 主持互动的基本原理的理解。