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Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension.

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Title: Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension.
Authors: Wimmer, Moritz I. (AUTHOR), Bartolomaeus, Hendrik (AUTHOR), Anandakumar, Harithaa (AUTHOR), Chen, Chia‐Yu (AUTHOR), Vecera, Valentin (AUTHOR), Kedziora, Sarah (AUTHOR), Kamboj, Sakshi (AUTHOR), Schumacher, Fabian (AUTHOR), Pals, Sidney (AUTHOR), Rauch, Ariana (AUTHOR), Meisel, Jutta (AUTHOR), Potapenko, Olena (AUTHOR), Yarritu, Alex (AUTHOR), Bartolomaeus, Theda U. P. (AUTHOR), Samaan, Mariam (AUTHOR), Thiele, Arne (AUTHOR), Stürzbecher, Lucas (AUTHOR), Geisberger, Sabrina Y. (AUTHOR), Kleuser, Burkhard (AUTHOR), Oefner, Peter J. (AUTHOR)
Source: Acta Physiologica. Nov2024, Vol. 240 Issue 11, p1-17. 17p.
Subjects: Diastolic blood pressure, Systolic blood pressure, Laboratory rats, Shotgun sequencing, Gut microbiota
Abstract: Aims: Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats. Methods: Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II‐dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry. Results: Metformin treatment increased the production of short‐chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end‐diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. In vitro, acetate and propionate altered M1‐like gene expression in macrophages, reinforcing anti‐inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure. Conclusion: Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators. [ABSTRACT FROM AUTHOR]
Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension.
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  Data: <searchLink fieldCode="AR" term="%22Wimmer%2C+Moritz+I%2E%22">Wimmer, Moritz I.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bartolomaeus%2C+Hendrik%22">Bartolomaeus, Hendrik</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Anandakumar%2C+Harithaa%22">Anandakumar, Harithaa</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Chia‐Yu%22">Chen, Chia‐Yu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vecera%2C+Valentin%22">Vecera, Valentin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kedziora%2C+Sarah%22">Kedziora, Sarah</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kamboj%2C+Sakshi%22">Kamboj, Sakshi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schumacher%2C+Fabian%22">Schumacher, Fabian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pals%2C+Sidney%22">Pals, Sidney</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rauch%2C+Ariana%22">Rauch, Ariana</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Meisel%2C+Jutta%22">Meisel, Jutta</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Potapenko%2C+Olena%22">Potapenko, Olena</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yarritu%2C+Alex%22">Yarritu, Alex</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bartolomaeus%2C+Theda+U%2E+P%2E%22">Bartolomaeus, Theda U. P.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Samaan%2C+Mariam%22">Samaan, Mariam</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Thiele%2C+Arne%22">Thiele, Arne</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stürzbecher%2C+Lucas%22">Stürzbecher, Lucas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Geisberger%2C+Sabrina+Y%2E%22">Geisberger, Sabrina Y.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kleuser%2C+Burkhard%22">Kleuser, Burkhard</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Oefner%2C+Peter+J%2E%22">Oefner, Peter J.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Acta+Physiologica%22">Acta Physiologica</searchLink>. Nov2024, Vol. 240 Issue 11, p1-17. 17p.
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  Data: <searchLink fieldCode="DE" term="%22Diastolic+blood+pressure%22">Diastolic blood pressure</searchLink><br /><searchLink fieldCode="DE" term="%22Systolic+blood+pressure%22">Systolic blood pressure</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+rats%22">Laboratory rats</searchLink><br /><searchLink fieldCode="DE" term="%22Shotgun+sequencing%22">Shotgun sequencing</searchLink><br /><searchLink fieldCode="DE" term="%22Gut+microbiota%22">Gut microbiota</searchLink>
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  Label: Abstract
  Group: Ab
  Data: Aims: Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats. Methods: Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II‐dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry. Results: Metformin treatment increased the production of short‐chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end‐diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. In vitro, acetate and propionate altered M1‐like gene expression in macrophages, reinforcing anti‐inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure. Conclusion: Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/apha.14226
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        Text: English
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