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

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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.