Establishing a collaboration to enable effective nutritional targeting of age-related immune decline and intestinal microbial dysbiosis

尽管人们现在的寿命更长了，但许多老年人仍然患有严重的疾病。我们知道，生活方式因素在决定这种不健康风险方面很重要。这些生活方式因素包括营养过剩（摄入过多高能量食物）和营养不足（摄入太少必需营养素）。炎症和免疫系统功能低下是导致老年性疾病的主要原因。重要的是，这些免疫变化也限制了对流感疫苗等公共卫生措施的反应。新的研究表明，生活在肠道内的微生物，被称为肠道微生物群，对整体健康有重大影响。随着我们年龄的增长，这些微生物的多样性下降，而且一些微生物和它们的成分可以突破肠道屏障进入血液。这对老年人的免疫系统构成威胁，并增加患病风险。通过本项目的多学科工作，我们将解决的挑战是对老年人营养、肠道微生物群和炎症/免疫衰退之间联系的了解不足。我们计划以一种方式工作，将为英国在这一领域的国家研究能力提供一个步骤的改变，通过我们的合作，我们将开发一个虚拟的营养免疫学研究中心，该中心将向任何希望参与这一研究领域的人开放。我们将通过以下方式为研究界提供强有力的领导：a)举办一系列三次研讨会，讨论和界定该领域的关键方法问题；B)制定和分发标准操作程序，以开展营养、免疫系统和肠道微生物群相互作用的研究；C)发表三篇学术论文，概述人类营养和人类营养临床试验、营养免疫学和肠道微生物组领域的最佳研究实践。此外，我们将开展一项可行性研究，以测试我们在老年人群中招募和实施高水平完成和依从性干预的能力，测试我们的标准操作程序，并在必要时对其进行改进，处理和交换样本，整合和理解我们的发现，并生成所需的可靠试点信息，以设计针对肠道微生物群的更明确的营养方法试验。老年人的炎症和免疫系统。可行性研究将包括给参与者单独或同时服用维生素D和益生菌，为期3个月。测试维生素D和益生菌有很好的理由，因为老年人通常维生素D水平较低，肠道微生物也会发生变化，这两种情况都会影响炎症和免疫系统正常运作的能力。可行性研究的关键结果将是了解对炎症、免疫功能和肠道微生物群多样性的影响和影响。我们将使用数学建模来系统地整合结果数据，以帮助描述老年人和我们的干预措施背景下这些结果之间复杂的相互作用，并增强对这些结果的理解。我们将把我们的样本和数据提供给其他研究人员。此外，我们将规划未来的试验并制定战略，以确保我们合作的可持续性。为了扩大我们的影响力，我们将与更广泛的学术界、公众、工业界、非政府组织和相关领域的现有欧洲项目建立联系。

Although people are now living longer, many older people live with significant illness. We know that lifestyle factors are important in determining this risk of ill health. These lifestyle factors include both overnutrition (too much energy-dense foods being consumed) and undernutrition (too few essential nutrients being consumed). Inflammation and a poorly functioning immune system are major contributors to age-related disease. Importantly, these immune changes also limit responses to public health measures like influenza vaccinations. New research has shown that the microbes that live inside the gut, called the intestinal microbiota, have a major influence on overall health. As we age the diversity of these microbes declines and also some microbes and their components can breach the intestinal barrier and enter the bloodstream. This is a threat to older people's immune system and contributes to risk of illness. The challenge we will address, through multidisciplinary working in this project, is the poor understanding of the links between nutrition, the intestinal microbiota and inflammation/immune decline in older adults. We plan to work in a way that will provide a step-change in the UK's national research capability in this field and through our collaboration we will develop a virtual nutritional immunology research centre that will be open to anyone who wishes to participate in this research area. We will provide strong leadership to the research community through:a) hosting a series of three workshops to discuss and define key methodological issues in the area; b) the development and distribution of standard operating procedures to carry out research studying the interactions of nutrition, the immune system and the intestinal microbiota; c) the publication of three academic papers outlining best practice for research in the areas of human nutrition and human nutrition clinical trials, nutritional immunology and the intestinal microbiome. In addition, we will conduct a feasibility study to test our ability to recruit and carry out interventions in older populations with high levels of completion and compliance, to test our standard operating procedures and refine them if necessary, to process and exchange samples, to integrate and understand our findings, and to generate the robust pilot information that is needed to design more definitive trials of nutritional approaches for targeting the intestinal microbiota, inflammation and the immune system in older people. The feasibility study will involve giving participants vitamin D and probiotics, alone and together for a period of 3 months. There is a good rationale for testing both vitamin D and probiotics, because older people often have low vitamin D status and altered intestinal microbes both of which can affect inflammation and the ability of the immune system to function properly. Key outcomes of the feasibility study will be to understand the effects and impact on inflammation, immune function and intestinal microbiota diversity. We will use mathematical modelling to integrate the resulting data systematically aiding the characterisation, and enhancing the understanding, of the complex interactions among these outcomes in the contexts of older people and our interventions. We will make our samples and data available to other researchers. Further, we will plan future trials and develop a strategy to ensure sustainability of our collaboration. To broaden our influence we will link with the wider academic community, the public, industry, non-governmental organisations, and existing European projects in relevant areas.