Every year, more than 10% of children hospitalised in Africa for severe acute malnutrition die within two to three weeks, and deaths continue after discharge. The problem is that doctors cannot measure what is going wrong inside these children’s guts. Impaired digestion, poor absorption, a leaky gut lining, and disrupted gut bacteria all contribute to malnutrition, but the tools to assess these processes in low-resource settings are inadequate. Several clinical trials are testing new treatments, but without reliable ways to measure gut function, it is impossible to tell whether an intervention works. This project will develop a suite of practical tools to fill that gap. The researchers will use stable isotope tracers to measure digestion and absorption, fluorescent markers to detect gut leakiness, advanced immunology to track bacterial responses, genomic sequencing to map gut bacteria, and spectroscopy to analyse bacterial function. If successful, these tools will allow clinicians to evaluate new treatments for malnutrition in Africa with real precision. They may also prove useful for diagnosing and monitoring rare gut disorders in children and adults in well-resourced countries, where response to nutritional therapy remains difficult to assess.
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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.
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