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

营养不良影响着全世界4.62亿人，其中1.65亿儿童身高发育不良，5200万儿童消瘦（非常瘦弱）。急性和慢性营养不良（“发育迟缓”）与低收入和中等收入国家的重大健康和经济负担有关。在急性营养不良方面，儿童严重急性营养不良的管理进展甚微，死亡率仍然很高。支持SAM的因素是复杂和多因素的，最终导致正常肠道细菌（或微生物群）的破坏，可用的重要营养物质的量减少，肠道屏障（粘膜）破坏导致功能改变，例如粘膜免疫力受损和细菌（革兰氏阴性菌）从肠道泄漏到体内，导致败血症和高死亡风险。除此之外，贫困和缺乏食物导致营养不良，还有水质差和环境病原体负担增加（蠕虫和卫生条件差），所有这些都导致肠道无法吸收蛋白质和重要营养素。这形成了一个恶性循环，导致营养不良儿童的不良结果。.我们计划采取一种替代方法，而不是仅仅增加再喂养计划中的蛋白质和能量摄入量，因为这些计划未能解决肠道屏障功能差和致病性肠道细菌（微生物组）的根本问题。我们的总体战略是制定一项工作计划，以了解营养不良、病原体负担、肠道屏障功能、肠道微生物组和健康结果之间的关系，并制定针对具体情况的营养战略，以克服中低收入国家儿童发育关键阶段的营养挑战。我们提出的营养饲料将侧重于豆类（豆类）蛋白质和碳水化合物，因为后者在肠道中代谢产生脂肪酸，有助于修复肠道屏障功能，并将微生物组改变为更“健康”的微生物组，减少重要营养素的损失。最终改善营养状况，降低败血症的风险。研究问题：我们有六个优先研究问题，这些问题是我们长期研究计划的基础。这些是：1.了解肠道屏障功能障碍在急性和慢性营养不良中的作用？2.使用豆类饲料是否有助于修复肠道屏障，促进健康的肠道微生物组，并改善营养不良的健康状况？3.在高病原体负担下营养不良儿童的蛋白质需求是什么？4.为了帮助中低收入国家的农民，当地生产的豆类作物能否帮助满足生命关键阶段的蛋白质和重要营养素？5.需要进行哪些干预研究，以证明豆类作物在管理低收入中等收入国家人口营养不良方面的益处？6.如何在低收入中等收入国家人口中可持续地增加豆类消费？为了开始实现这一目标，我们将把研究界与长期目标的发展，重新审视和完善目前的建议，大量营养素喂养方案，以减少发病率和死亡率与肠道屏障功能障碍的中低收入国家。

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.