Gut microbiota in heart failure and related interventions

Abstract

Heart failure (HF) is a sophisticated syndrome with structural or functional impairment of ventricular filling or ejection of blood, either causing symptoms and signs or being asymptomatic. HF is a major global health issue affecting about 64.3 million people worldwide. The gut microbiota refers to the complex ecosystem of microorganisms, mainly bacteria, in the gut. Studies have revealed that the gut microbiota is associated with many diseases ranging from neurodegenerative diseases to inflammatory bowel disease and cardiovascular diseases. The gut hypothesis of HF suggests that low cardiac output and systemic circulation congestion would cause insufficient intestinal perfusion, leading to ischemia and intestinal barrier dysfunction. The resulting bacterial translocation would contribute to inflammation. Recent studies have refined the hypothesis that changes of metabolites in the gut microbiota have a close relationship with HF. Thus, the gut microbiota has emerged as a potential therapeutic target for HF due to both its critical role in regulating host physiology and metabolism and its pivotal role in the development of HF. This review article aims to provide an overview of the current understanding of the gut microbiota's involvement in HF, including the introduction of the gut hypothesis of HF, its association with HF progression, the potential mechanisms involved mediated by the gut microbiota metabolites, and the impact of various interventions on the gut microbiota, including dietary interventions, probiotic therapy, fecal microbiota transplantation, antibiotics, and so on. While the gut hypothesis of HF is refined with up-to-date knowledge and the gut microbiota presents a promising target for HF therapy, further research is still needed to further understand the underlying mechanisms between gut microbiota and HF, the efficacy of these interventions, and contribute to the health of HF patients.

Keywords: gut microbiota; heart failure; short‐chain fatty acids; trimethylamine N‐oxide.

Figure 1

The gut hypothesis of heart failure. The gut hypothesis of HF proposes that low cardiac output and systemic circulation congestion lead to reduced intestinal perfusion, resulting in ischemia and consequently intestinal barrier disruption. A damaged barrier with increased permeability allows bacterial translocation and endotoxins to release into the bloodstream, contributing to inflammation and worsening HF.

Figure 2

Metabolite changes contribute to HF. TMAO contributes to HF by promoting cardiac fibrosis and hypertrophy, boosting inflammation and endothelial dysfunction, inducing oxidation, and disturbing thermogenesis. A decrease in SCFA levels has been linked to HF, as SCFAs play an important role in preventing cardiac hypertrophy and fibrosis, reducing inflammation, and satisfying energy metabolism. Therefore, maintaining sufficient levels of SCFAs in the body may be beneficial in the prevention and treatment of HF. TMAVA promotes cardiac hypertrophy and reduces fatty acid oxidation. PAGln increases the susceptibility of ventricular arrhythmias in HF. HF, heart failure; PAGln, phenylacetylgutamine; SCFAs, short‐chain fatty acids; TMAO, trimethylamine N‐oxide; TMAVA, N,N,N‐trimethyl‐5‐aminovaleric acid.

Figure 3

Metabolism of short‐chain fatty acids (SCFAs). SCFAs are mainly produced from dietary fiber by the gut microbiota and used as an energy source by the mitochondria. Unmetabolized SCFAs enter portal circulation, and a small amount of SCFAs reach systemic circulation.

Figure 4

Intervention on the gut microbiota in HF. Interventions targeting the gut microbiota in HF include dietary interventions, such as the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, probiotic therapy, fecal microbiota transplantation, antibiotics, and other potential approaches.