Scripties UMCG - Rijksuniversiteit Groningen
 
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Influence of an enteric infection on the intestinal epithelial barrier function of severely malnourished mice

(2017) Onverwagt, E. (Emmy)

Severe acute malnutrition (SAM) is a global problem that is associated with a high mortality rate in children. Even after hospitalization, up to 35% of SAM patients do not survive. Mortality is linked to the development of diarrhea indicating intestinal dysfunction. Intestinal pathogens are frequently found but the pathophysiology of the intestinal dysfunction during enteric infection in the context of SAM is not well understood. In this study, several pilot experiments were performed to develop a murine model of SAM and enteric infection. It focused on the effects of this double insult on intestinal histology and intestinal epithelial barrier function. A model was developed in which mice received a diet containing 1% protein and were given a seven-day infection with 10⁷ CFU C. rodentium. The combined results of the pilot projects revealed that enteric infection caused a higher infection load in malnourished mice compared to control mice associated with more diarrhea, epithelial cell damage and an attenuated distribution of claudin 3, a marker of epithelial barrier function. It had no influence on the distribution of claudin 7, another marker of epithelial barrier function, and the amount of claudin 3 and claudin 7. Furthermore, enteric infection caused weight loss, crypt hyperplasia and goblet cell loss. In future, this murine model could be used to test novel interventions against SAM and hence lower its case fatality rate.






 
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