Wimmer, Moritz I. and Bartolomaeus, Hendrik and Anandakumar, Harithaa and Chen, Chia-Yu and Vecera, Valentin and Kedziora, Sarah and Kamboj, Sakshi and Schumacher, Fabian and Pals, Sidney and Rauch, Ariana and Meisel, Jutta and Potapenko, Olena and Yarritu, Alex and Bartolomaeus, Theda U. P. and Samaan, Mariam and Thiele, Arne and Stuerzbecher, Lucas and Geisberger, Sabrina Y. and Kleuser, Burkhard and Oefner, Peter J. and Haase, Nadine and Loeber, Ulrike and Gronwald, Wolfram and Forslund-Startceva, Sofia K. and Mueller, Dominik N. and Wilck, Nicola (2024) Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension. ACTA PHYSIOLOGICA, 240 (11). ISSN 1748-1708, 1748-1716
Full text not available from this repository. (Request a copy)Abstract
AimsMetformin 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.MethodsMale 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.ResultsMetformin 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.ConclusionMetformin 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | cardiac remodeling; hypertension; inflammation; metformin; microbiome; short-chain fatty acids |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Nov 2025 07:10 |
| Last Modified: | 26 Nov 2025 07:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65272 |
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