Developing multiscale models of digestion to enable targeted product solutions for nutrition and metabolic health

The gastrointestinal tract is a continuous organ with different complex environments along its length aimed at the efficient absorption of food. The impact that food can make, through an number of mechanisms, on appetite regulation and glucose homeostasis can occur in the gastrointestinal tract from the mouth to the colon. However, the greatest impact on satiety and glucose regulating hormones released from the gastrointestinal tract is seen after 30-60 minutes following the consumption of food. There is little understanding of the relationship between early food digestion and the metabolic processes that drive mechanisms that effect appetite and glucose homeostasis. Our aim is to develop multiscale models of digestion incorporating engineering and theoretical physics methodologies to enable targeted product solutions for nutrition and metabolic health. We will develop a fundamental understanding which provides a vital basis to understanding a range of scientific and technological questions outlined below:
1. Rational design of dietary components to maintain a healthy weight is critically important to enable healthy ageing. In England, 60% of the adult population is overweight or obese, which imposes a major public health and financial burden. Therefore, it becomes a priority to understand how dietary components can maintain energy and glucose homeostasis across the lifespan.
2. On a global scale, rational design of foodstuffs is required to ensure enhanced calorie availability and the most efficient use of food resources that will be relevant to the developing world.
3. Understanding of the healthy gut to inform models of diseases of the digestive system is needed.
This is particularly timely because of recent advances in the new techniques that are becoming available (multi-scale modelling, physical imaging). We are also able to build on advances under the DRINC projects, which have contributed new understanding of the biochemical and biophysical digestive environment. The work also builds on the harmonised INFOGEST protocol from an EU-based project. In addition, as a result of the sandpit, we have identified novel expertise across disciplines which has a very obvious role to play in deciphering the complexities of digestion of food structures.

Our aim is to develop multiscale models of early digestion of food to enable targeted product solutions for nutrition and metabolic health. Upon selection of materials to study, our approach is summarised below:
a) We shall study the biochemical digestion of food materials in the gastric and duodenal phase by subjecting these materials to the INFOGEST protocol. We will collect samples of the digestive fluid at regular intervals and store them for subsequent determination of nutrient release kinetics. In order to combine the physical and biochemical aspects of digestion, an in vitro gastric digestion will be set up and the digestive output will be used immediately as a starting material for an existing Peristaltic Duodenal Model which mimics peristalsis as it occurs in the small intestine.
b) The rheology of the digesta will be measured as a function of residence time. The mechanical loads quantified from the Duodenal Peristaltic experiments described in part a) above will be used as boundary conditions to simulate damage and breakdown in computer simulations. The level of deformation and breakdown will be correlated with the nutrient release profile determined biochemically described above. The particle breakdown will also feed into the starting conditions for the simulations described in part c) below.
c) An in silico mesoscale simulation that follows how macromolecules/bacteria move in highly complex fluids such as dense polymer solutions will be used to examine how molecules move across the mucus layer to reach signalling receptors and compared to results for the organoid experiments described below in part d).
d) We will use our developed intestinal systems (human small intestinal gut organoids) to understand the interplay between metabolites and gut hormone release. The results will be used to validate the simulations described in part c) above.

This project addresses a number of UK's major diet-related health challenges (obesity and diabetes). Understanding how to rationally design foods, by understanding early digestion has the potential for long term impact on a wide range of stakeholders from consumers to policy makers. The outputs of the research will impact on the following stakeholder groups:-

Food Industry: The outputs from this project will enable the food industry to develop a new generation of foods targeted at reducing the incidence of common non-communicable disease such as obesity and type 2 diabetes. Further research will allow the process to be applied to a large portfolio of foods. Results from the project will inform efforts to ensure foods that have an improved health profile have high acceptability comparable to currently-available foods, making it more convenient for consumers to adopt healthier options. Food with high nutritional impact is a growing sector of the food industry and robust scientific evidence of positive health benefits arising from this and future projects will support health claims and further growth and give the UK food industry a competitive advantage.
Consumers: Individual consumers will have new knowledge regarding the health benefits of certain foods, together with a wider choice of manufactured foods with specific, proven health benefits. Care must be taken with the health communication aspects as consumption of these foods may only be effective as part of a healthy balanced diet. In the long term, the benefits of reducing the prevalence of diabetes will impact on lifelong health and well-being of individuals and improve the quality of life into old age.
Pharmaceutical Industry: The generic principles involved in this research are expected to stimulate further research to improve the targeted delivery of nutritional compounds, polymers and other therapeutic and health promoting compounds to the colon.
National Health Service and Government: 60% of the UK population are overweight or obese. The number of individuals diagnosed with type 2 diabetes in the UK has roughly doubled since 1996 to about 2.6 million, with over 70% of cases being over the age of 55. The cost to the UK economy of obesity is estimated to be £27 billion. The direct cost to the NHS and other health care providers for treating type 2 diabetes and related conditions is around £10 billion per year (approx. 10% of the NHS budget). The total cost of diabetes to the nation including direct care, loss of working days due to sickness and loss of productivity is estimated to be £23.7 billion. Any reduction in the prevalence of diabetes would have a huge impact through fewer hospital admissions, fewer surgical interventions and fewer prescriptions, hence lower health costs. The basic knowledge generated from this project, and further research targeted at foods which have a public health impact, will also help Government agencies to develop dietary advice for individuals at risk from developing diabetes in later life.

To maximise impact, we will assemble an Advisory Panel composed of various stakeholders including academics, beneficiaries, end users and industry. The panel will meet three times during the project to review progress and advise on future directions, application and exploitation. In addition, two further open meetings will be held at the end of the project to consult with a broader group of stakeholders.