Manipulation of the gut microbiota by the use of prebiotic fibre does not override a genetic predisposition to heart failure.

Increasing evidence supports a role for the gut microbiota in the development of cardiovascular diseases such as hypertension and its progression to heart failure (HF). Dietary fibre has emerged as a modulator of the gut microbiota, resulting in the release of gut metabolites called short-chain fatty acids (SCFAs), such as acetate. We have shown previously that fibre or acetate can protect against hypertension and heart disease in certain models. HF is also commonly caused by genetic disorders. In this study we investigated whether the intake of fibre or direct supplementation with acetate could attenuate the development of HF in a genetic model of dilated cardiomyopathy (DCM) due to overexpression of the cardiac specific mammalian sterile 20-like kinase (Mst1). Seven-week-old male mice DCM mice and littermate controls (wild-type, C57BL/6) were fed a control diet (with or without supplementation with 200 mM magnesium acetate in drinking water), or a high fibre diet for 7 weeks. We obtained hemodynamic, morphological, flow cytometric and gene expression data. The gut microbiome was characterised by 16S rRNA amplicon sequencing. Fibre intake was associated with a significant shift in the gut microbiome irrespective of mouse genotype. However, neither fibre or supplementation with acetate were able to attenuate cardiac remodelling or cardiomyocyte apoptosis in Mst1 mice. Furthermore, fibre and acetate did not improve echocardiographic or hemodynamic parameters in DCM mice. These data suggest that although fibre modulates the gut microbiome, neither fibre nor acetate can override a strong genetic contribution to the development of heart failure in the Mst1 model.

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

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.