The Role of Nutrients, Gut Dysfunction and the Gut Microbiome in Determining Health Outcomes in Undernutrition

Lead Research Organisation: Imperial College London

Abstract

Undernutrition affects 462 million people world-wide with 165 million children having stunted height and 52 million children are wasted (very thin). Both acute and chronic malnutrition ('stunting') are associated with significant health and economic burdens in low and middle income countries (LMICs). In acute malnutrition, little progress has been made in the management of severe acute malnutrition (SAM) in children, where mortality (death) remains high. The factors
underpinning SAM are complex and multifactorial, ultimately resulting in disruption of the normal gut bugs (or microbiota), reduced ammounts of vital nutrients being available, the barrier (mucosa) of the gut breaking down causing altered function
such as impaired mucosal immunity and leakiness of the bugs from the gut (gram negative bacteria) into the body causing septicaemia and high risk of mortality. On top of this, poverty and the lack of foods causing undernutrition there is also poor quality water and increased environmental pathogen burden (worms and poor sanitation) all leading to an increase the
gut not being able to absorp protein and vital nutrients. These form a vicious cycle and contribute to the poor outcomes in undernourished children. .
Rather than just increase the amount of proten and energy giving in refeeding programmes, which have failed to tackle the underlying problems of the poor gut barrier function and pathogenic gut bacterial (microbiome) we plan to take an alternative approach. Our overarching strategy is to develop a programme of work to understand the relationships between
undernutrition, pathogen burden, gut barrier function, the gut microbiome, and health outcomes, and to develop nutritional strategies that are context-specific to overcome nutritional challenges at key stages of child development in LMICs. The nutritional feed we propose will focus upon legume (pulses) based proteins and carbohydrates since the latter are metabolised in the gut to produce fatty acids which can help repair gut barrier function and alter the micriobiome into a
more 'healthy' one, with less loss of vital nutrients. Ultimately improving nutrition statue and reducing the risk of septicaemia.
Research Questions: We have six priority research questions which underpin our long-term research plans. These are:
1. To understand the role of gut barrier dysfunction in both acute and chronic malnutrition?
2. Do the use of legumes feeds help repair the gut barrier and promote a healthy gut microbiome and lead to improved health outcomes in malnutrition?
3. What are the protein requirements of malnourished children under high pathogen burden?
4. In order to help farmers in low middle income countries (LIMCs) can locally-produced legume crops help meet the protein and vital nutrients at key stages of life?
5. What intervention studies are needed to generate evidence of the benefit of legume pulses in the management of undernutrition in LMIC populations?
6. How can legume consumption be increased sustainably across LMIC populations?
To begin to achieve this we will bring the research community together with the long term aim of developing, revisit and refine current recommendations of macronutrient feeding regimens to reduce morbidity and mortality associated with gut barrier dysfunction in LMICs.

Technical Summary

Undernutrition affects 462 million people world-wide with 165 million children being stunted and 52 million wasted. The factors underpinning SAM are complex and multifactorial, ultimately resulting in disruption of the normal gut microbiota,reduced assimilation of vital nutrients, altered gut barrier function, impaired mucosal immunity and increased risk of gram negative bacteraemia which form a vicious cycle. Environmental enteric disease (EED) shares common features of gut dysfunction with SAM including villous atrophy, disruption of the normal gut microbiota, disruption of the gut barrier function, increased local and systemic inflammation and bacterial translocation which adversely affect growth and cognitive development. This programme will bring together leading experts from across the scientific community to investigate how legumes (pulses) can offer a joint solution to the supply of quality protein and fermentable carbohydrate to support a competent diverse gut microbiome and optimum gut barrier function needed in SAM and EED. The focus of this application is to facilitate the development of a substantive multi-disciplinary research programme to enhance the management of malnutrition in LMICs. To achieve this, we will begin with a kick-off meeting at beginning of the project to set a research development agenda in four key areas: 1. Improved assessment of gut barrier dysfunction 2. Fermentable carbohydrate as a solution to gut barrier dysfunction and improving amino acid supply as a method of optimising small intestinal function. 3. Determine the protein requirements of malnourished children under high pathogen burden 4. Legumes as a solution to meeting protein and micronutrient requirements and improved gut barrier function 5. Sustainable intake of legumes Our long-term plan is to develop and refine current recommendations of macronutrient feeding regimens to reduce morbidity and mortality associated with gut barrier dysfunction in LMIC.

Publications

10 25 50
 
Description HUNGER white paper
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
URL https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper...
 
Description White paper
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
URL https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper...
 
Title New methodology to assess gastrointestinal function in undernutrition 
Description The method is trying to find a minimally in way of assessing the health of the gI tract 
Type Of Material Biological samples 
Year Produced 2018 
Provided To Others? No  
Impact Nothing yet the tool is being rested 
URL https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper...
 
Description HUNGER Collaberation 
Organisation John Innes Centre
Department Department of Crop Genetics
Country United Kingdom 
Sector Private 
PI Contribution Imperial College London is the lead for the project
Collaborator Contribution Quadram - Expertise in in vitro digestion John Innes Centre - Crop Genetics University of Glasgow - Stable isotope technology St John's - expertise in stunting Wellcome Trust - SAM Queen Mary University - Paediatric gastroenterology
Impact Two networking meeting have been run very successfully wit the partners White paper has been written - https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2017
 
Description HUNGER Collaberation 
Organisation Quadram Institute Bioscience
Department Food & Health Programme
Country United Kingdom 
Sector Academic/University 
PI Contribution Imperial College London is the lead for the project
Collaborator Contribution Quadram - Expertise in in vitro digestion John Innes Centre - Crop Genetics University of Glasgow - Stable isotope technology St John's - expertise in stunting Wellcome Trust - SAM Queen Mary University - Paediatric gastroenterology
Impact Two networking meeting have been run very successfully wit the partners White paper has been written - https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2017
 
Description HUNGER Collaberation 
Organisation Queen Mary University of London
Department Blizard Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Imperial College London is the lead for the project
Collaborator Contribution Quadram - Expertise in in vitro digestion John Innes Centre - Crop Genetics University of Glasgow - Stable isotope technology St John's - expertise in stunting Wellcome Trust - SAM Queen Mary University - Paediatric gastroenterology
Impact Two networking meeting have been run very successfully wit the partners White paper has been written - https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2017
 
Description HUNGER Collaberation 
Organisation St Johns Research Institute
Country India 
Sector Academic/University 
PI Contribution Imperial College London is the lead for the project
Collaborator Contribution Quadram - Expertise in in vitro digestion John Innes Centre - Crop Genetics University of Glasgow - Stable isotope technology St John's - expertise in stunting Wellcome Trust - SAM Queen Mary University - Paediatric gastroenterology
Impact Two networking meeting have been run very successfully wit the partners White paper has been written - https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2017
 
Description HUNGER Collaberation 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Imperial College London is the lead for the project
Collaborator Contribution Quadram - Expertise in in vitro digestion John Innes Centre - Crop Genetics University of Glasgow - Stable isotope technology St John's - expertise in stunting Wellcome Trust - SAM Queen Mary University - Paediatric gastroenterology
Impact Two networking meeting have been run very successfully wit the partners White paper has been written - https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2017
 
Description HUNGER Collaberation 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution Imperial College London is the lead for the project
Collaborator Contribution Quadram - Expertise in in vitro digestion John Innes Centre - Crop Genetics University of Glasgow - Stable isotope technology St John's - expertise in stunting Wellcome Trust - SAM Queen Mary University - Paediatric gastroenterology
Impact Two networking meeting have been run very successfully wit the partners White paper has been written - https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2017
 
Description Determining Health Outcomes in Undernutrition 
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 The researcher in the Hunger project all met in London to drive forward the project. The aim was to establish the working groups and helpe
Year(s) Of Engagement Activity 2018
URL https://www.imperial.ac.uk/hunger-project/
 
Description Determining health outcomes in undernutrition 
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 Workshop attended by 25 researchers to drive the project forward
Year(s) Of Engagement Activity 2019
URL https://www.imperial.ac.uk/hunger-project/
 
Description Tracked research meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave and expert talk and led a debate on under-nutrition and the role of the gut
Year(s) Of Engagement Activity 2018