Abstract
Undernutrition is a major public health problem leading to 1 in 5 of all deaths in children under 5 years. Undernutrition leads to growth stunting and/or wasting and is often associated with environmental enteric dysfunction (EED). EED mechanisms leading to growth failure include intestinal hyperpermeability, villus blunting, malabsorption and gut inflammation. As non-invasive methods for investigating gut function in undernourished children are limited, pre-clinical models are relevant to elucidating the pathophysiological processes involved in undernutrition and EED, and to identifying novel therapeutic strategies. In many published models, undernutrition was induced using protein or micronutrient deficient diets, but these experimental models were not associated with EED. Enteropathy models mainly used gastrointestinal injury triggers. These models are presented in this review. We found only a few studies investigating the combination of undernutrition and enteropathy. This highlights the need for further developments to establish an experimental model reproducing the impact of undernutrition and enteropathy on growth, intestinal hyperpermeability and inflammation, that could be suitable for preclinical evaluation of innovative therapeutic intervention.
Highlights
Acute malnutrition is a major public health problem in low-income countries, affecting 51 million children under the age of five [1]
We have reviewed and discussed the available animal models that may be useful to mimic the clinical features of Severe acute malnutrition (SAM) and enteric dysfunction (EED)
Understanding the physiological mechanisms involved during an episode of undernutrition associated with enteropathy is a critical step in developing novel therapeutic strategies
Summary
Acute malnutrition is a major public health problem in low-income countries, affecting 51 million children under the age of five [1]. EED has been associated with an altered therapeutic response and fecal calprotectin, a sign of inflammation, and has been related with mortality [7] These triumvirate, i.e., chronic intestinal inflammation, hyperpermeability and villous blunting, lead to reduced nutrient uptake, which affects growth and child development [4,8] and enters into a vicious circle of worsening undernutrition state. As studying gut barrier function in undernourished children is challenging, preclinical models have been developed to enable a better understanding of the mechanisms behind undernutrition and/or enteropathy. These models were intended for the evaluation of novel therapeutics in undernutrition and/or EED.
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