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.

多项研究结果表明，肠道微生物群和屏障功能可能对健康维护和长寿产生重大影响，从而调节健康寿命。此外，肠道屏障功能受损、肠道微生物群组成变化、TH1/TH2 细胞平衡以及肠道氧化还原状态的改变被认为对于老年人常见的低度炎症的发生至关重要。我们最近发现，小鼠的衰老与肠道微生物群组成的变化和肠道屏障功能的受损有关，同时伴随着小肠上部 iNOS 和促炎介质表达水平的下降。然而，肠道微生物群、屏障功能、免疫系统与衰老相关的退化和衰退之间的相互作用仅被部分了解。从这一背景出发，本研究项目的目的是（1）描绘肠道稳态和屏障功能的改变在什么年龄开始发生，以及这些变化是否与肠道微生物群组成和NO生物利用度的改变以及小肠和大肠组织中TH1细胞的流行率有关，以及（2）确定通过iNOS合成NO在衰老相关的改变中的作用。 肠道微生物群组成和屏障功能。在此，我们将特别关注饮食成分和能量生物利用度的作用，以及确定新的靶向策略，以防止与衰老相关的肠道微生物群组成和屏障功能的改变。因此，我们的目标还在于加深对微生物与宿主相互作用的基本原理的理解。