The impact of nutritional ketosis in gut microbiota and in cardiac function in heart failure

Heart failure (HF) is a debilitating disease with a sifnificant clinical and economic impact on the world’s population, resulting from na impaired (diastolic dysfunction) or ejection capacity (systolic dysfunction) in the right (RV) or left ventricle (LV). HF has been subclassified into two forms, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) based on the value of ejection fraction (EF). Heart failure with preserved ejection fraction (HFpEF) affects more than half of the patients diagnosed with heart failure. Various lifestyle risk factos assiciated with diet, diabetes, obesity, and hypertension have been linked as probable causes for faster disease progression. Apart from symptom alleviation and strict controlo f the comorbidities, no effective therapeutic options exist to improve prognosis or target the metabolic abnormalities associated with HFpEF. Recent evidence suggests that chronic inflmmation plays a significant role in HFpEF pathophysiology. In this contexto, gut dysbiosis is known to cause chronic low-grade inflammation and thus accelerate the development of cardiovascular disease. This causal link seems to result from the fact that gut dysbiosis weakens the intestinal Wall, leadind to the leakage of damaging metabolities from specific bactéria into the bloodstream, contributing to chronic inflammation. Growing evidence seems to support the direct therapeutic potential of ketones on several carddiac diseases but the beneficial impact of ketogenic diet on gut microbiota and its indirect cardiac impact remains higly controversial and warrants further research. In this study, it was possible to characterize changes in the intestinal microbiota such as a decrease in microbial richness and diversity and the growth of bactéria activated by chronic inflammation in 2 different rat models of HF: a model of HFpEF with metabolic syndrome and in a modelo f HFrEF induced by monocrotaline (MCT). Furthermore, we evaluated the impacto f a high-fat, low-carbohydrate diet ketogenic diet (KD) on the microbiota and its influence on metabolismo and cardiac function during disease progression in both models: KD improved glycemia, insulin resistance and the oral glucose tolerance test. Furthermore, supplementation with ketone salts was tested i the standard diet fed HFpEF model and proved to be the most advantageous dietary intervention since ketosis benefits were obtained without the strictness of a ketogenic diet