Gaining insight into the determinants of mortality in hospitalized severely malnourished children: a translational and intestine focused approach

Severe malnutrition remains a major cause of morbidity and mortality in children under the age of five in low- and middle income countries. Risk factors for death during treatment in hospital are diarrhoea, intestinal and systemic inflammation and reduced levels of short-chain fatty acids in the intestine. This combination of risk factors supports the idea that a decreased function of the intestine plays an important role in the deaths of severely malnourished children. Due to ethical and practical limitations of investigating this in severely malnourished children, we developed two models: a mouse model and mini-gut (intestinal organoids) model of severe malnutrition. With the use of the mouse model and mini-guts we learned that a disruption in the energy factories of the cell (mitochondria) and a defect in the recycling of cell organelles (autophagy) possible play an important role in the decrease in intestinal function in severely malnourished children. A treatment that improves these two aspects, improved the function of the intestine in these two models. The mouse model and mini-guts can provide better insight in the underlying mechanisms of decreased intestinal function. In addition, treatments can be tested in these models, which hopefully leads to a better treatment and survival of severely malnourished children in low- and middle income countries.