Effect of Dietary Fibre Intake and the Gut Microbiota in a Model of Heart Failure

Introduction: Although dietary intake of fruit and vegetables is associated with lower incidence of cardiovascular disease, the mechanism involved is not clear. Consumption of a diet high in fibre increases gut microbiota populations that generate short chain fatty acids (SCFAs) such as acetate, which has a protective role in experimental models of inflammatory diseases. Hypothesis: We hypothesised that SCFAs, including acetate, would attenuate the development of cardiac fibrosis in a mineralocorticoid-excess (MRE) model, given that inflammation has also been implicated in cardiac remodelling. Methods: Mice were fed control chow (47.6% fibre), high fibre chow (72.7% fibre) or water supplemented with acetate for 3 weeks, and then submitted to sham (uninephrectomy+1% salt) or MRE (uninephrectomy+1% salt+ DOCA tablet) surgeries (n=11-14/group). At the end of 6 weeks, cardiac structure (cardiac weight index and fibrosis by Mason trychrome) and function (by echocardiography) were examined. The gut microbiota was determined by next-generation sequencing of the 16S gene, and RNA-sequencing established the mechanisms involved. Results: Compared to MRE mice fed a normal diet, those fed a high fibre diet or acetate had significantly less cardiac hypertrophy, perivascular and interstitial cardiac fibrosis, and improved cardiac function (all P<0.05). Mice fed a high fibre diet or acetate had a profound effect on the activity circadian clock genes and decreased TGF-β and immune response. The protective effects of high fibre and acetate were accompanied by a decrease in the ratio of bacteria from the phylum Firmicutes compared to Bacteroidetes in both sham and DOCA groups (0.56 control vs 0.14 fibre vs 0.18 acetate, P=0.0005). Conclusions: Our study supports that dietary high fibre intake, through the SCFA acetate, can prevent heart failure by reducing cardiac fibrosis and improving cardiac function during MRE. This was accompanied by changes in the gut microbiota, supporting a gut-heart connection in the prevention of heart disease.