BBSRC Institute Strategic Programme: Food Microbiome and Health (FMH) - Partner Grant

Globally, poor diet accounts for 10 million (22%) of all adult deaths (every year
with cardiovascular disease as the leading cause. The UK has both the highest obesity rates and worst healthy life
expectancy in Europe, hence the urgent need to switch to a more nutritionally balanced diet. Growing environmental,
ethical and health concerns are motivating transition to plant-rich diets, a trend that will increase because of global
population and climate change. The changes in our dietary habits provide unique opportunities for designing novel plantbased
foods that improve health. However, this dietary shift also brings challenges as plant-based diets contain processed
carbohydrate-rich foods with high glycaemic/ calorie content that tend to have lower availability of key macronutrients, such
as protein, micronutrients including vitamins D and B12, and minerals such as iron, zinc and iodine. Many of the nutrient
challenges associated with plant-based diets are being addressed through processes such as biofortification and new
technologies such as gene-editing. There is need to understand the effect of these approaches not only on food structure
and composition, but also how they impact the GI microbiome and host responses.
Strategy, aims and objectives: A key, achievable strategy for addressing these challenges is to focus on the relationships
between plant-based food, the GI microbiome and human health. Consequently, our overall aim is to unpick the
complicated relationship between particular plant-based foods, GI microbes and health through mechanistic research into
these interactions.
The FMH ISP is organised into four themes (Ts) comprising targeted objectives that reflect the pathway and processing of
plant-based food by the body to provide health benefits:
- T1 Food structure/composition/digestion and nutrient release in the GIT;
- T2 Role of plant-based foods and macro- and micro-nutrients on the GIT microbiota structure and function;
- T3 How nutrients impact on the integrity and physiology of key organ systems e.g. the GIT itself, liver and brain;
- T4 Exploiting the knowledge gained from our mechanistic studies to evaluate new food and microbiota-based
interventions that promote or improve long-life health in proof-of-concept human trials.
Our research aims to provide a mechanistic understanding of how the structure and composition of plant-based foods can
be used to improve health and reduce the threat of disease through its interaction with the GIT microbiome. The ISP is
organised into four themes (Ts) with state-of-the-art, specialist and enabling technologies.
In T1, we will use plant-based foods that can be modified through gene editing/ biofortification/ processing to determine
how these foods are digested and the released nutrients transformed and/or absorbed throughout the GIT using QIB's
unique in vitro digestion and intestinal fermentation models (e.g. SHIME); food analytics; metabolomics and vitamin
diagnostics.

This project represents the University of Surrey's contribution to the delivery of the following Institute Strategic Programme Grant: BBSRC Institute Strategic Programme: Food Microbiome and Health BB/X011054/1 for which our expertise in strategies for improving vitamin D status in the general population and in 'at risk' groups is highly complementary (in Theme 4).

We have over 30 years experience in designing and implementing human nutrition randomised controlled trials (RCT) to prevent micronutrient deficiency, with specific expertise in vitamin D. We have applied this knowledge extensively at the UK (H.M. Government SACN) and the EU (EFSA) level with respect to setting vitamin D dietary requirements (SACN) and tolerable upper limits for vitamin D (EFSA).

Our three objectives are as follows:

1. Prepare the designed vitamin D biofortification RCT using gene-edited (GE) tomatoes and placebo tomatoes for submittance to the relevant Academic Institution(s) and NHS Ethic Committee(s) and register the Vitamin D RCT to Clinical Trials.Gov.

2. Implement the biofortified vitamin D GE tomato vs placebo tomato RCT including: (i) selection and screening of potential subjects; (ii) measurement of habitual dietary intake and lifestyle characteristics at baseline, 4 weeks and 8 weeks intervention; (iii) assessment of UVB exposure at baseline, 4 weeks and 8 weeks; (iv) determination of the health-benefits of the biofortified vitamin D GE tomato with specific reference to changes in vitamin D status and markers of calcium metabolism and musculo-skeletal health.

3. Define the benefits - (in relation to health, economic, sustainability) at the general population level and in 'at-risk' minority groups of increasing vitamin D intake and improving vitamin D status using plant-based approaches and undertake specific dietary vitamin D modelling work using 'BIG' datasets (including the UK Biobank, the UK NDNS and the USA NHANES).