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

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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.