Title: Core/NRF Fellowship: Effects of multiple micronutrient and amino acid supplementation on intestinal function and microbiome-host interactions in environmental enteropathy: a study in Zambian adults
Funder: CORE

Abstract: In very broad terms what is the problem that this project is going to address?Stunting affects one third of children in the developing world, equivalent to over 150 million children. This has lifelong detrimental effects on health and productivity – these children do not just grow into short adults. Compared to their unaffected peers, they are more likely to die, develop more slowly, achieve less in school, and earn less as adults. Stunting is therefore a major global health priority.Unfortunately, efforts to improve stunting by increasing food intake or by reducing infectious disease burden have not been very effective. There is therefore now great interest within the global health community in a condition known as environmental enteropathy, which is thought could underlie all of these observations.Environmental enteropathy is a symptomless disorder which is extremely common in stunted populations. It is thought to result from living in unsanitary conditions and being continually exposed to bacteria and other microbes. It is characterised by numerous abnormalities of small bowel structure and function, which predisposes to poor absorption of nutrients and allows gut microbes to enter the blood stream. This results in persistent low levels of inflammation, which puts excessive demands on the body's immune system and takes resources away from growing and developing.Environmental enteropathy is still poorly understood, and there are no established treatments for it. This study aims to examine some of the processes underlying this intriguing condition in more detail, and to see if there is any benefit from giving a dietary supplement of amino acids (the fundamental 'building blocks' of proteins) and / or micronutrients (minerals and vitamins).What will this project do and how long it will take?We will be examining the effects of an amino acid and / or micronutrient supplement on environmental enteropathy. Approximately 80 healthy Zambian adults with environmental enteropathy will be divided into four treatment groups: placebo; daily amino acid supplement; daily micronutrient supplement; or both. We will include healthy HIV positive and negative volunteers. HIV is known to have a significant effect on the gut immune system, even in people who are otherwise well and don't have any symptoms We therefore suspect that this will affect how their gut responds to the conditions that are thought to result in environmental enteropathy. The supplements will be given for four months.The study participants will provide blood, urine and stool samples. We will examine the first part of their small bowel in microscopic detail using an exciting and novel endoscopy technique, known as confocal laser endomicroscopy. The blood, urine, stool, endoscopy pictures and small bowel tissue samples will be taken before and after the supplementation period, and analysed for markers of gut inflammation, 'leakiness', and human-microbe interactions. We will look for (1) effects before and after supplementation; (2) differences between people who have had micronutrients and / or amino acids to people who haven't; and (3) differences between HIV positive and negative individuals.The clinical trial element and collection of samples will take place over a period of six to nine months, and the whole project will take 2-3 years. The project is due to begin in September 2014 and a final report will be completed by September 2017.What will ‘success’ look like for this project?We expect to discover interesting and novel insights not only into the mechanisms of environmental enteropathy, but also into how nutrition influences the gut immune response and gut inflammation. This will allow us and others to develop further research ideas and clinical trials, both into environmental enteropathy and other conditions characterised by an abnormal gut immune response.I hope that this study will also provide evidence for a simple nutritional intervention for this globally importa


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.1 PHARMACEUTICALS
Health categories: DISPUTED AETIOLOGY AND OTHER;ORAL AND GASTROINTESTINAL