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

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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.