Modeling undernutrition with enteropathy in mice

Abstract Undernutrition is a global health issue leading to 1 out 5 all deaths in children under 5 years. Undernutrition is often associated with environmental enteric dysfunction (EED), a syndrome associated with increased intestinal permeability and gut inflammation. We aimed to develop a novel mu...

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Autores principales: Emmeline Salameh, Marine Jarbeau, Fanny B. Morel, Mamane Zeilani, Moutaz Aziz, Pierre Déchelotte, Rachel Marion-Letellier
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Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/33b32b979bd0443bbf98f2a5a612b9c5
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spelling oai:doaj.org-article:33b32b979bd0443bbf98f2a5a612b9c52021-12-02T18:48:01ZModeling undernutrition with enteropathy in mice10.1038/s41598-020-72705-02045-2322https://doaj.org/article/33b32b979bd0443bbf98f2a5a612b9c52020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-72705-0https://doaj.org/toc/2045-2322Abstract Undernutrition is a global health issue leading to 1 out 5 all deaths in children under 5 years. Undernutrition is often associated with environmental enteric dysfunction (EED), a syndrome associated with increased intestinal permeability and gut inflammation. We aimed to develop a novel murine model of undernutrition with these EED features. Post-weaning mice were fed with low-protein diet (LP) alone or combined with a gastrointestinal insult trigger (indomethacin or liposaccharides). Growth, intestinal permeability and inflammation were assessed. LP diet induced stunting and wasting in post-weaning mice but did not impact gut barrier. We therefore combined LP diet with a single administration of indomethacin or liposaccharides (LPS). Indomethacin increased fecal calprotectin production while LPS did not. To amplify indomethacin effects, we investigated its repeated administration in addition to LP diet and mice exhibited stunting and wasting with intestinal hyperpermeability and gut inflammation. The combination of 3-weeks LP diet with repeated oral indomethacin administration induced wasting, stunting and gut barrier dysfunction as observed in undernourished children with EED. As noninvasive methods for investigating gut function in undernourished children are scarce, the present pre-clinical model provides an affordable tool to attempt to elucidate pathophysiological processes involved in EED and to identify novel therapeutic strategies.Emmeline SalamehMarine JarbeauFanny B. MorelMamane ZeilaniMoutaz AzizPierre DéchelotteRachel Marion-LetellierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Emmeline Salameh
Marine Jarbeau
Fanny B. Morel
Mamane Zeilani
Moutaz Aziz
Pierre Déchelotte
Rachel Marion-Letellier
Modeling undernutrition with enteropathy in mice
description Abstract Undernutrition is a global health issue leading to 1 out 5 all deaths in children under 5 years. Undernutrition is often associated with environmental enteric dysfunction (EED), a syndrome associated with increased intestinal permeability and gut inflammation. We aimed to develop a novel murine model of undernutrition with these EED features. Post-weaning mice were fed with low-protein diet (LP) alone or combined with a gastrointestinal insult trigger (indomethacin or liposaccharides). Growth, intestinal permeability and inflammation were assessed. LP diet induced stunting and wasting in post-weaning mice but did not impact gut barrier. We therefore combined LP diet with a single administration of indomethacin or liposaccharides (LPS). Indomethacin increased fecal calprotectin production while LPS did not. To amplify indomethacin effects, we investigated its repeated administration in addition to LP diet and mice exhibited stunting and wasting with intestinal hyperpermeability and gut inflammation. The combination of 3-weeks LP diet with repeated oral indomethacin administration induced wasting, stunting and gut barrier dysfunction as observed in undernourished children with EED. As noninvasive methods for investigating gut function in undernourished children are scarce, the present pre-clinical model provides an affordable tool to attempt to elucidate pathophysiological processes involved in EED and to identify novel therapeutic strategies.
format article
author Emmeline Salameh
Marine Jarbeau
Fanny B. Morel
Mamane Zeilani
Moutaz Aziz
Pierre Déchelotte
Rachel Marion-Letellier
author_facet Emmeline Salameh
Marine Jarbeau
Fanny B. Morel
Mamane Zeilani
Moutaz Aziz
Pierre Déchelotte
Rachel Marion-Letellier
author_sort Emmeline Salameh
title Modeling undernutrition with enteropathy in mice
title_short Modeling undernutrition with enteropathy in mice
title_full Modeling undernutrition with enteropathy in mice
title_fullStr Modeling undernutrition with enteropathy in mice
title_full_unstemmed Modeling undernutrition with enteropathy in mice
title_sort modeling undernutrition with enteropathy in mice
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/33b32b979bd0443bbf98f2a5a612b9c5
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AT marinejarbeau modelingundernutritionwithenteropathyinmice
AT fannybmorel modelingundernutritionwithenteropathyinmice
AT mamanezeilani modelingundernutritionwithenteropathyinmice
AT moutazaziz modelingundernutritionwithenteropathyinmice
AT pierredechelotte modelingundernutritionwithenteropathyinmice
AT rachelmarionletellier modelingundernutritionwithenteropathyinmice
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