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

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.

The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease

“…Interestingly, Li et al showed that elevated blood pressure is transferrable through microbiota, when fecal samples from hypertensive human donors were transplanted to germ-free mice. Furthermore, Marques et al proposed that a high-fibre diet changes the murine gut microbiota, thus preventing the development of hypertension and heart failure [67]. The authors of this study also suggested that this might be due to short chain fatty acids (i.e.…”

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

“…Both fiber and acetate decreased gut dysbiosis as 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 [128]. These data suggest that the gut microbiome contributes to the association between diet high in fruits/vegetables and lower incidence of hypertension.…”

“…Marques and colleagues [128] examined the effect of control diet compared with high-fiber or acetate-supplemented diet in mineralocorticoid excess-treated mice. Both fiber and acetate decreased gut dysbiosis as measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens.…”

Gut Microbiota, a Rising Star in Hypertension

“…And total dairy, low-fat dairy, and milk were inversely and linearly associated with a lower risk of hypertension [50]. As is well known, that fiber is good for the gut, reports also suggest that a diet rich in fiber alter the gut microbiota population and increase the abundance of acetate-producing bacteria [24]. The beneficial effects of fiber might be explained by the generation and distribution of one of the primary metabolites of the gut microbiota, the SCFA [51].…”

“…A diet rich in fiber led to changes in the gut microbiota and thus prevent the development of hypertension. This change could be explained by the metabolism product of the gut microbiota, the short-chain fatty acid (SFCA) [24]. The SCFA, primary acetate, propionate, and butyrate, is the endpoint product of the fermentation of dietary fibers by the anaerobic intestinal microbiota [25].…”