Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice

Abstract Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-...

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Autores principales: Amélie Bravard, Céline Gérard, Clémence Defois, Bérengère Benoit, Kassem Makki, Emmanuelle Meugnier, Dominique Rainteau, Jennifer Rieusset, Murielle Godet, Hubert Vidal
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:a5a104bc960247cfb2331d8a4c0ee8be2021-12-02T17:08:44ZMetformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice10.1038/s41598-021-95117-02045-2322https://doaj.org/article/a5a104bc960247cfb2331d8a4c0ee8be2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95117-0https://doaj.org/toc/2045-2322Abstract Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days and treated with metformin by gavage (300 mg/day/kg body weight) during the HFS diet. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the different regions of the small intestine. It also induced beneficial modification of secondary bile acid profile in the caecum, with a reduction of deoxycholic acid and lithocholic acid levels and increased abundance of ursodeoxycholic acid and tauroursodeoxycholic acid, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes of the microbiota composition in the lumen of the different regions of the intestine. Metformin induced a marked increase in the abundance of Akkermansia muciniphila in the lumen all along the gut and counteracted the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). Therefore, the present work clearly emphasises the role of all the regions of the intestinal tract in the beneficial action of the antidiabetic drug metformin in a prediabetic mouse model.Amélie BravardCéline GérardClémence DefoisBérengère BenoitKassem MakkiEmmanuelle MeugnierDominique RainteauJennifer RieussetMurielle GodetHubert VidalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Amélie Bravard
Céline Gérard
Clémence Defois
Bérengère Benoit
Kassem Makki
Emmanuelle Meugnier
Dominique Rainteau
Jennifer Rieusset
Murielle Godet
Hubert Vidal
Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
description Abstract Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days and treated with metformin by gavage (300 mg/day/kg body weight) during the HFS diet. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the different regions of the small intestine. It also induced beneficial modification of secondary bile acid profile in the caecum, with a reduction of deoxycholic acid and lithocholic acid levels and increased abundance of ursodeoxycholic acid and tauroursodeoxycholic acid, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes of the microbiota composition in the lumen of the different regions of the intestine. Metformin induced a marked increase in the abundance of Akkermansia muciniphila in the lumen all along the gut and counteracted the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). Therefore, the present work clearly emphasises the role of all the regions of the intestinal tract in the beneficial action of the antidiabetic drug metformin in a prediabetic mouse model.
format article
author Amélie Bravard
Céline Gérard
Clémence Defois
Bérengère Benoit
Kassem Makki
Emmanuelle Meugnier
Dominique Rainteau
Jennifer Rieusset
Murielle Godet
Hubert Vidal
author_facet Amélie Bravard
Céline Gérard
Clémence Defois
Bérengère Benoit
Kassem Makki
Emmanuelle Meugnier
Dominique Rainteau
Jennifer Rieusset
Murielle Godet
Hubert Vidal
author_sort Amélie Bravard
title Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
title_short Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
title_full Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
title_fullStr Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
title_full_unstemmed Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
title_sort metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/a5a104bc960247cfb2331d8a4c0ee8be
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