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

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.

The challenge we will address is the limited understanding of links between nutrition, microbial diversity and inflammation/immune senescence in older adults. Our project will provide a step-change in the UK's research capability in this field and through our multidisciplinary collaboration we will develop a virtual nutritional immunology research centre open to all who wish to participate. We will provide leadership through a) hosting a series of three workshops; b) the development and distribution of standard operating procedures; c) the publication of three papers (one per workshop) outlining best practice for research in the areas of human nutrition and human nutrition clinical trials, nutritional immunology and the intestinal microbiome. We will conduct a feasibility study to test our ability to successfully recruit and conduct interventions in older adults with high levels of completion and compliance, test our standard operating procedures, process and exchange samples, integrate and understand our data, and generate robust pilot data for more definitive multi-centre trials of nutritional approaches for targeting the intestinal microbiota and the immune system in older people. The feasibility study will involve an intervention in 80 people aged over 70 years with vitamin D and probiotics, given alone and together over 3 months. Older people often have low vitamin D status and intestinal dysbiosis both of which can affect low-grade inflammation and immune competence. Key outcomes of the feasibility study will relate to the impact of the interventions on inflammation, immune function and intestinal microbiota. We will use mathematical modelling to understand the interactions among these outcomes in the context of older people and of our interventions. We will plan future trials and develop a strategy to ensure sustainability of our collaboration. We will link with the wider academic community, the public, industry, NGOs, and existing relevant European projects.

The planned research partnership and its activity is in a highly topical area with huge interest from academia, health professionals, industry, regulators, consumers and policy makers. The partnership will offer a series of three research workshops and a dissemination workshop, a number of standardised operating procedures, three publications, a database, a mathematical model and a bank of biological samples and will provide an infrastructure of multi-disciplinary expertise to offer to stakeholders, so creating a virtual centre for research in nutritional immunology. The partnership will make links with stakeholders and have significant impact.

Academia: The significant benefit of the partnership's activities to the academic community is outlined under "Academic Beneficiaries". In summary, academics will benefit from access to a series of three workshops and the outcome of those workshops, to a number of standardised operating procedures, to three publications establishing best practice, to a mathematical model, to a database containing anonymised phenotypic data about 80 older people, to biological samples from older people, and to an infrastructure of multi-disciplinary expertise through a virtual centre for research in nutritional immunology. This will significantly enhance the UK's research capacity and quality in this area. In addition we will establish links with relevant research projects in the UK, Ireland and Continental Europe.

The health care sector and health professionals: It is recognised that immunological dysfunction related to ageing (i.e. low grade inflammation and decline in cell mediated immunity) is a major barrier to maintaining the health and wellbeing of a population characterised by an increased number of older individuals. This represents a growing personal, societal and economic burden in the face of a limited financial and other resource. Consequently, identification of novel mechanisms that regulate inflammation and immune function that are potential targets for strategies to support immune health, particularly through the diet, will be of considerable benefit both in terms of sustained immune health and lower economic burden. Thus, the findings of this project will be of marked interest and benefit to government organisations such as Public Health England and the NHS.

Industry: The food, supplements, clinical nutrition and infant nutrition industries are highly interested in "immune health", the role of intestinal dysbiosis in loss of health and well-being, the use of probiotics and nutraceuticals like vitamin D, and the growing number of older people which creates commercial opportunities. Thus, industry will be very interested in the proposed programme of activities, the infrastructure that the partnership will establish, and the findings from the feasibility study. We will have an industry member on our Management Team and at the end of the project we will host a dissemination workshop specifically for industry.

Regulators and Policy Makers: UK and EU regulators like Public Health England and European Food Safety Authority will be interested in the partnership and in the findings from the feasibility study.

NGOs: Organisations that support translation of research into the commercial and regulatory arenas (e.g. ILSI Europe, ISAPP) will be interested in the partnership, the workshops and publications, and the findings from the feasibility study.

Consumers and Patients: Older people and their families are likely to want to seek independent solutions to remaining healthy. Thus, older people, and charities like Age UK that lobby for the interests of older people, will to be very interested in the existence of a partnership focussing upon their specific health needs and in the findings from the feasibility study. Representatives will be invited to attend the end of project dissemination workshop and PPI event. We will have an older people's representative on our Management Team.