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Research Article
Hubert Vidal
Université de Lyon, Laboratoire CarMeN, INSERM U1060, INRA U1397, INSA Lyon, Université Claude Bernard Lyon1
Corresponding Author
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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 that occur in the different regions of the intestinal tract in response to metformin treatment, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days. Metformin treatment by gavage (300 mg/day/kg body weight) during the HFS diet improved glucose tolerance. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the small intestine, and induced beneficial modification of secondary bile acid profile in the caecum, with reduction in DCA and LCA levels and increased abundance of UDCA and TUDCA, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes in the microbiota composition in the lumen of the different regions of the gut, counteracting the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). In addition, metformin promotes a strong increase in the abundance of Akkermansia muciniphila in the intestinal lumen all along the gut. 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.
Keywords
Type 2 diabetes, metformin, gut microbiota, bile acids
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No competing interests reported.
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Hubert Vidal
Université de Lyon, Laboratoire CarMeN, INSERM U1060, INRA U1397, INSA Lyon, Université Claude Bernard Lyon1
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 23 Mar, 2021
No community comments so far
Review #4 received
Received 12 Apr, 2021
Review #1 received
Received 12 Apr, 2021
Review #2 received
Received 12 Apr, 2021
Review #3 received
Received 12 Apr, 2021
Reviewer #9 agreed
On 22 Mar, 2021
Reviewer #15 agreed
On 22 Mar, 2021
Reviewer #10 agreed
On 22 Mar, 2021
Reviewer #19 agreed
On 22 Mar, 2021
Reviewer #4 agreed
On 22 Mar, 2021
Reviewer #12 agreed
On 22 Mar, 2021
Reviewer #16 agreed
On 22 Mar, 2021
Reviewer #17 agreed
On 22 Mar, 2021
Reviewer #7 agreed
On 22 Mar, 2021
Reviewer #18 agreed
On 22 Mar, 2021
Reviewer #3 agreed
On 22 Mar, 2021
Reviewer #14 agreed
On 22 Mar, 2021
Reviewer #11 agreed
On 22 Mar, 2021
Reviewer #5 agreed
On 22 Mar, 2021
Reviewer #1 agreed
On 22 Mar, 2021
Reviewer #2 agreed
On 22 Mar, 2021
Reviewer #6 agreed
On 22 Mar, 2021
Reviewers invited
Invitations sent on 22 Mar, 2021
Editor assigned
On 22 Mar, 2021
Editor invited
On 22 Mar, 2021
Submission checks complete
On 22 Mar, 2021
First submitted
On 19 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 that occur in the different regions of the intestinal tract in response to metformin treatment, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days. Metformin treatment by gavage (300 mg/day/kg body weight) during the HFS diet improved glucose tolerance. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the small intestine, and induced beneficial modification of secondary bile acid profile in the caecum, with reduction in DCA and LCA levels and increased abundance of UDCA and TUDCA, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes in the microbiota composition in the lumen of the different regions of the gut, counteracting the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). In addition, metformin promotes a strong increase in the abundance of Akkermansia muciniphila in the intestinal lumen all along the gut. 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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