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 fibre diet and supplementation with the short-chain fatty acid (SFCA) 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 fibre 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 fibre modified the gut microbiota populations and increased the abundance of acetate-producing bacteria, independently of mineralocorticoid-excess. Both fibre and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens. Compared to mineralocorticoid-excess mice fed a control diet, both high fibre diet and acetate supplementation significantly reduced systolic and diastolic blood pressure, cardiac fibrosis and left ventricular hypertrophy. Acetate had similar effects and also markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fibre and acetate were accompanied by the down-regulation of cardiac and renal Egr1, a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis and inflammation. We also observed the up-regulation of a network of genes involved in circadian rhythm in both tissues, while down-regulated the renin-angiotensin system in the kidney and mitogen-activated protein kinases (MAPK) signalling in the heart. CONCLUSIONS—: A diet high in fibre led to changes in the gut microbiota which played a protective role in the development of cardiovascular disease. The favourable effects of fibre may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the SCFA acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function.