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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| Format: | Article |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-95117-0 |
| _version_ | 1819198706090508288 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T03:04:42Z |
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| id | doaj.art-a5a104bc960247cfb2331d8a4c0ee8be |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T03:04:42Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a5a104bc960247cfb2331d8a4c0ee8be2022-12-21T18:02:21ZengNature PortfolioScientific Reports2045-23222021-08-0111111210.1038/s41598-021-95117-0Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed miceAmélie Bravard0Céline Gérard1Clémence Defois2Bérengère Benoit3Kassem Makki4Emmanuelle Meugnier5Dominique Rainteau6Jennifer Rieusset7Murielle Godet8Hubert Vidal9Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Centre de Recherche Saint-Antoine, INSERM U938, Sorbonne UniversitéLaboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Laboratoire CarMeN, INSERM U1060, INRAE U1397, Université de Lyon, Université Claude Bernard Lyon1Abstract 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.https://doi.org/10.1038/s41598-021-95117-0 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-95117-0 |
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