High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice
Open accessAbstract
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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In a rodent hypertension study, either a high-fiber diet or acetic acid alone resulted in reduced blood pressure and adverse cardiac remodeling.
“One example includes a recent rodent hypertension study in which either a high-fiber diet (a prebiotic) or acetic acid alone (a gut microbial product) resulted in reduced blood pressure and adverse cardiac remodeling168.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [168]
A significant proportion of SCFAs produced in the distal bowel is reabsorbed from the gut lumen by facilitated apical solute transport via multiple transporters and passive diffusion.
“A significant proportion of the SCFAs produced in the distal bowel is reabsorbed from the gut lumen by facilitated apical solute transport via multiple different transporters114–117 as well as via passive (concentration-dependent) diffusion118.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [118]
Interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects in animal models and in patients with hypertension.
“Finally, studies in animal models and in patients with hypertension have reported that interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects87,92–99.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [95]
In DOCA-salt hypertensive mice, a high-fibre diet leads to substantial reductions in both systolic and diastolic blood pressure (~20 mmHg).
“In DOCA-salt hypertensive mice, a high-fibre diet led to substantial reductions in both SBP and DBP (~20 mmHg)95.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [95]
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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
- Venue
- Circulation
- Published
- 2017-03-07
- Volume
- 135
- Issue
- 10
- Pages
- 964-977
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- 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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