Beyond the gut: Systemic levels of short-chain fatty acids are altered in patients with heart failure

Background & aim: The gut microbiome produces short-chain fatty acids (SCFAs), which serve as a substantial energy source and provide a link between the microbiome and (cardiac) metabolism. It has been demonstrated that the composition of the microbiome is altered in patients with heart failure (HF), but whether circulating levels of SCFAs are altered in HF is unknown. Methods & results: Serum concentrations of the SCFAs acetate, propionate, and butyrate were measured in 205 patients with HF and in 54 healthy controls, using isotope dilution liquid chromatography-tandem mass spectrometry. Of the patients with HF, 99 had HF with a reduced ejection fraction (HFrEF) and 106 had HF with mildly-reduced or preserved ejection fraction (HFmrEF/HFpEF). Healthy controls were age and sex matched to the HFrEF patients. Serum concentrations of acetate and propionate were significantly lower in patients with HF than in healthy controls, whereas butyrate levels were higher in patients with HF. Analyses by HF type revealed that acetate and propionate levels were lower in both HFrEF and HFpEF/HFmrEF patients in comparison to healthy controls. However, butyrate levels were observed to be lower in patients with HFmrEF/HFpEF in comparison to healthy controls, while they were higher in patients with HFrEF. Conclusions: In patients with HF, serum levels of acetate and propionate are lower across the HF spectrum, whereas serum butyrate levels are elevated in HFrEF, but lower in HFmrEF/HFpEF. These alterations in SCFA profiles suggest a microbiome-driven metabolic dysregulation, which appears to differ between HF subtypes.