NOVEL TOOLS FOR EVALUATING INTESTINAL DYSFUNCTION IN CHILDREN AND ADULTS WITH MALNUTRITION DISORDERS

非洲患有SAM的儿童的死亡率仍然远远高于人们通常所认为的水平，通常超过10%，即使在儿童住院的2-3周内，如果有任何并发症。即使在出院后，这种情况也会继续发生。几项临床试验正在进行中，试图找到降低死亡率的干预措施，但由于我们一次性使用的工具不足，无法测量消化受损、吸收受损、肠道免疫力下降和肠道细菌平衡紊乱等过程，这些试验受到了阻碍。即使在高度完善的卫生保健系统中，这些过程也很难评估，但在非洲，这是评估新干预措施的一个非常困难的障碍。我们提出的这项研究将使用稳定(非放射性)同位素技术来测量消化和吸收，荧光示踪剂来测量肠道衬里的渗漏，先进的免疫学来研究肠道细菌分子的反应，基因组测序来研究肠道细菌的平衡，以及先进的光谱学来分析这些肠道细菌的功能。在这个过程中，我们将对患有严重急性营养不良的儿童了解很多，并将产生新的分析肠道功能的工具。然后，这些工具反过来可能有助于研究罕见的儿童和成人肠道功能障碍，即使在资源丰富的国家，这些疾病往往需要复杂的营养支持，遗憾的是，在这些情况下，仍然很难评估对治疗的反应。

Mortality in children in Africa with SAM is still far higher than commonly appreciated, usually over 10% even for the 2-3 weeks that a child is in hospital if there is any sort of complication. It continues to occur even after discharge from hospital care. Several clinical trials are under way to try and find interventions to reduce this mortality, but they are hampered by the inadequacy of the tools at our disposable for measuring processes like impaired digestion, impaired absorption, failure of gut immunity, and disturbances of the balance of bacteria in the intestine. Even in highly refined health care systems these processes are difficult to assess, but in Africa this is a very tough obstacle to evaluating novel interventions. The study we propose will use stable (non-radioactive) isotope techniques to measure digestion and absorption, fluorescent tracers to measure leakiness of the lining of the gut, advanced immunology to study responses to molecules derived from bacteria in the gut, genomic sequencing to study the balance of bacteria in the gut, and advanced spectroscopy to analyse the function of those gut bacteria. In the process we will learn a great deal about children with severe acute malnutrition, and will generate new tools for analysing gut function. These tools may then, in turn, be useful for studying rare disorders of gut function in children and adults even in well-resourced countries, conditions which often require complex nutritional support and in which it is still, sadly, very hard to evaluate response to therapy.