From gut to heart: the emerging role of dietary fermentable fiber in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a multisystemic syndrome that accounts for more than half of all heart failure cases and causes a substantial burden of morbidity and mortality. In contrast to heart failure with reduced ejection fraction, few disease-modifying therapies exist for HFpEF, reflecting differences in pathophysiology. Low fermentable fiber (FF) intake, gut dysbiosis, and depletion of short-chain fatty acids (SCFAs), microbial metabolites central to immune, metabolic, and vascular homeostasis, are increasingly linked to the pathophysiology of HFpEF. Here, we synthesize preclinical and clinical evidence on FF and SCFAs and evaluate their therapeutic relevance to HFpEF. Preclinical studies demonstrate that FF supplementation or direct SCFA administration improves cardiometabolic function and attenuates cardiac remodeling through SCFA receptor signaling, enhanced nitric oxide bioavailability, reduced inflammation, and metabolic support of the energy-starved failing heart. Supporting the translational relevance of these findings, a systematic review of 27 human randomized controlled trials showed that FF interventions exert microbiome-mediated effects, enriching SCFA-producing taxa and augmenting fecal and circulating SCFA levels, while improving insulin sensitivity and reducing abdominal adiposity and low-density lipoprotein cholesterol. Direct SCFA supplementation increases SCFA availability and provides modest metabolic benefits, including reduced adiposity and liver fat. However, its effects are inconsistent. Collectively, these findings provide a mechanistic and translational rationale for FF-based interventions in HFpEF. To date, no clinical trials have evaluated the effects of FF on HFpEF-specific outcomes. Clinical studies are therefore needed to determine whether increasing FF intake can improve symptoms, cardiac function, and disease progression in HFpEF.