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Modeling undernutrition with enteropathy in mice.

Emmeline Salameh1,2,3, Marine Jarbeau1,2, Fanny B Morel3

  • 1Normandie Univ, INSERM Unit 1073, University of Rouen, 22 Boulevard Gambetta, 76000, Rouen, France.

Scientific Reports
|September 25, 2020
PubMed
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Researchers developed a new mouse model for childhood undernutrition and environmental enteric dysfunction (EED). This model mimics key EED features like gut barrier dysfunction, aiding the study of this global health issue.

Area of Science:

  • Pediatric Nutrition
  • Gastroenterology
  • Animal Models

Background:

  • Undernutrition causes 20% of deaths in children under five globally.
  • Environmental enteric dysfunction (EED) is linked to undernutrition, characterized by increased intestinal permeability and gut inflammation.
  • Existing models do not fully replicate EED's complex pathology.

Purpose of the Study:

  • To develop a novel murine model that replicates the key features of environmental enteric dysfunction (EED) associated with undernutrition.
  • To establish a pre-clinical tool for investigating EED pathophysiology and potential therapeutic strategies.

Main Methods:

  • Post-weaning mice were fed a low-protein (LP) diet.
  • The LP diet was combined with gastrointestinal insult triggers: indomethacin or lipopolysaccharides (LPS).

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  • Growth, intestinal permeability (fecal calprotectin), and gut inflammation were assessed.

    • Main Results:

    • LP diet alone caused stunting and wasting but not gut barrier dysfunction.
    • Combined LP diet and repeated indomethacin administration induced stunting, wasting, intestinal hyperpermeability, and gut inflammation.
    • LPS administration did not significantly increase fecal calprotectin.

    Conclusions:

    • A novel murine model combining a low-protein diet with repeated indomethacin successfully replicates undernutrition-associated EED.
    • This pre-clinical model offers a valuable tool for studying EED and identifying new therapeutic interventions.
    • The model's ability to mimic EED features provides a much-needed resource given the scarcity of noninvasive methods for studying gut function in affected children.