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

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

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.

Technical Summary

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.

Planned Impact

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.

Publications

10 25 50
 
Description We have developed a mathematical model of gastric emptying
We have developed new in vitro models to investigate early digestion
Exploitation Route At the moment it is difficult to say as the project is ongoing. This will be clear at the end of 2019
Sectors Agriculture, Food and Drink,Healthcare

 
Description BBSRC iCase
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2019 
End 09/2023
 
Description Early digestion group (MMOD) 
Organisation Mondelez International
Country United States 
Sector Private 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Early digestion group (MMOD) 
Organisation Nestlé Research Center
Country Switzerland 
Sector Private 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Early digestion group (MMOD) 
Organisation PepsiCo
Country United States 
Sector Private 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Early digestion group (MMOD) 
Organisation Pladis
Country United Kingdom 
Sector Private 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Early digestion group (MMOD) 
Organisation Quadram Institute Bioscience
Country United Kingdom 
Sector Academic/University 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Early digestion group (MMOD) 
Organisation University of Leeds
Department School of Food Science and Nutrition Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Early digestion group (MMOD) 
Organisation University of Nottingham
Department Faculty of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Early digestion group (MMOD) 
Organisation University of Oxford
Department Department of Physics
Country United Kingdom 
Sector Academic/University 
PI Contribution My team leads the collaberation to understand early digestion
Collaborator Contribution They bring scientific and commercial expertise to the project
Impact too early
Start Year 2016
 
Description Imperial Nestle Collaboration 
Organisation Nestlé Institute of Health Sciences
Country Switzerland 
Sector Private 
PI Contribution Developing research partnership
Collaborator Contribution Cutting edge science Knowledge of the market
Impact To early
Start Year 2016
 
Description Metabolite and nutrition partnership 
Organisation Murdoch University
Country Australia 
Sector Academic/University 
PI Contribution This partnership will develop links around food metabolomics a food strucutures
Collaborator Contribution The phenome centre at Murdock Univesity will provide anylitical techniques to understand food strucutre
Impact It is too early in the collaberation to have impact
Start Year 2019
 
Description Quadram Imperial Collaboration 
Organisation Quadram Institute Bioscience
Department Food & Health Programme
Country United Kingdom 
Sector Academic/University 
PI Contribution Human cutting edge research
Collaborator Contribution They provide the scientific hub for the collaberation
Impact Non at the present time
Start Year 2018
 
Description British Dietetics Association Obesity Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Spoke to expert dietitian about hte potential role of the gut microbiota in dietetic practice
Year(s) Of Engagement Activity 2020
URL https://www.eventbrite.co.uk/e/bda-obesity-group-annual-conference-2020-tickets-69660236643#
 
Description DRINC Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Spoke to 100 people about the results of our Primimg Food Partnership Grant
Year(s) Of Engagement Activity 2019
 
Description FENS conference Dublon 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Spoke to an audance of over 100 one food and the gut covering aspects from many of my awards
Year(s) Of Engagement Activity 2019
URL http://www.fens2019.org/
 
Description Food digestion meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 400 scientist attended a two day meeting. I present the impact of fermentable carbohydrate on appetite regulation. Good audience feed back
Year(s) Of Engagement Activity 2017
 
Description Food hackathon 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact 50 small to medium size enterprises will take part in a Hackaton aimed at finding a way forward and translation around legume foods and health
Year(s) Of Engagement Activity 2019,2020
URL https://www.imperial.ac.uk/events/95859/food-hack-2020-translating-nutritional-research-into-product...
 
Description Imperial Science Festival - dissemination to general public 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We had a two stands disseminating information in out work on dietary fibre and dietary assessment
Year(s) Of Engagement Activity 2017
URL http://www.imperial.ac.uk/festival/about/festival-2017/
 
Description NIHR Imperial College BRC open day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Over 500 people attended the Imperial College NIHR open day where we demonstrated out work in the NIHR BRC
Year(s) Of Engagement Activity 2019
URL https://imperialbrc.nihr.ac.uk/2019/09/22/nihr-imperial-research-open-day-friday-15th-november-2019/
 
Description Newsletter for MMOD project 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact WE produse a one page update on the project that is published every 3 months
Year(s) Of Engagement Activity 2017,2018
 
Description Presentaion to Cambridge metabolic group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact 50 post doctoral scientist attended the workshop on short chain fatty acids. The talk raised a number of questions and suggestion
Year(s) Of Engagement Activity 2018
 
Description Visit to Norway to talk to opinion makes about Nutrition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Talk to 15 Norwegian opinion leaders about the role of Nutrition in the prevention of non communicable disease highlighting my research
Year(s) Of Engagement Activity 2019
 
Description Workshop at DAVOS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact 120 people attended a science update at DAVOS. My talk was on the double hit of Malnutritiion
Year(s) Of Engagement Activity 2018
URL https://www.weforum.org/events/world-economic-forum-annual-meeting-2018