Cited by 1,065Gut microbiota and healthCardiac Fibrosis and RemodelingBlood Pressure and Hypertension Studies

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High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

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Marques, Francine Z., Nelson, Erin, Chu, Po-Yin, Horlock, Duncan, Fiedler, April, Ziemann, Mark, Tan, Jian K., Kuruppu, Sanjaya, Rajapakse, Niwanthi W., El-Osta, Assam, Mackay, Charles R., Kaye, David M.·2017·Circulation

DOI 10.1161/circulationaha.116.024545

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Abstract

Background: Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease. Methods: Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess–treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets. Results: We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens . Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal Egr1 , a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart. Conclusions: A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function.

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Authors: Marques, F. Z., Nelson, E., Chu, P.-Y., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., Mackay, C. R., & Kaye, D. M.
Affiliations: Baker Heart and Diabetes Institute (AU)
From Heart Failure Research Group (F.Z.M., E.N., P.-Y.C., D.H., A.F., N.W.R., D.M.K.) and Human Epigenetics Group (M.Z., A.E.-O.), Baker Heart and Diabetes Institute, Melbourne, Australia; Central Clinical School, Faculty of Medicine Nursing and Health Sciences (F.Z.M., A.E.-O., D.M.K.), Infection and Immunity Program, Monash Biomedicine Discovery Institute (J.K.T., C.R.M.), Department of Biochemistry and Molecular Biology (J.K.T., S.K., C.R.M.), and Department of Physiology (N.W.R.), Monash...
ORCID: Marques, Francine Z.
Ziemann, Mark
Kuruppu, Sanjaya
Rajapakse, Niwanthi W.
Mackay, Charles R.
Kaye, David M.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2017-03-07
Volume: 135
Issue: 10
Pages: 964-977
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.116.024545
OpenAlex: W2560340862
Cited by: 1,065
References: 47
Citations by year: 2026: 95 · 2025: 142 · 2024: 137 · 2023: 136 · 2022: 148 · 2021: 144 · 2020: 101 · 2019: 77 · 2018: 56 · 2017: 29
FWCI: 28.06
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Own your potential (DEAKIN) (submittedVersion)
Figshare (submittedVersion, cc-by)
Funders: Diabetes Australia Research Trust
Diabetes Australia
State Government of Victoria
Baker Heart and Diabetes Institute
Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords: high-fiber diet, acetate supplementation, gut microbiota, hypertension, heart failure, mineralocorticoid excess, Bacteroides acidifaciens, Firmicutes/Bacteroidetes ratio, myocardial fibrosis, left ventricular hypertrophy, renal fibrosis, EGR1, circadian rhythm, renin-angiotensin system, MAPK signaling, short-chain fatty acids, cardiovascular disease prevention
MeSH terms: Gastrointestinal Microbiome, Animals, Bacteria, Blood Pressure, Dietary Fiber, Disease Models, Animal, Fibrosis, Hypertension, Kidney, Male, Mice, Inbred C57BL, Myocardium, Organ Size, RNA, Ribosomal, 16S, Dietary Supplements, Principal Component Analysis, Gastrointestinal Tract, Mice, Transcriptome, Desoxycorticosterone Acetate

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High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

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