Gut microbiome - A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review

Abstract

Gut microbiome (GMB) has been increasingly recognized as a contributor to development and progression of heart failure (HF), immune-mediated subtypes of cardiomyopathy (myocarditis and anthracycline-induced cardiotoxicity), response to certain cardiovascular drugs, and HF-related comorbidities, such as chronic kidney disease, cardiorenal syndrome, insulin resistance, malnutrition, and cardiac cachexia. Gut microbiome is also responsible for the "gut hypothesis" of HF, which explains the adverse effects of gut barrier dysfunction and translocation of GMB on the progression of HF. Furthermore, accumulating evidence has suggested that gut microbial metabolites, including short chain fatty acids, trimethylamine N-oxide (TMAO), amino acid metabolites, and bile acids, are mechanistically linked to pathogenesis of HF, and could, therefore, serve as potential therapeutic targets for HF. Even though there are a variety of proposed therapeutic approaches, such as dietary modifications, prebiotics, probiotics, TMAO synthesis inhibitors, and fecal microbial transplant, targeting GMB in HF is still in its infancy and, indeed, requires further preclinical and clinical evidence. In this review, we aim to highlight the role gut microbiome plays in HF pathophysiology and its potential as a novel therapeutic target in HF.

Keywords: 3,3-dimethyl-1-butanol; Diet; Gut microbiome; Heart failure; SCFA; TMAO.

Figure 1.. “Gut hypothesis” of heart failure and its comorbidities.

Figure 1 shows that hemodynamic features of heart failure (HF), decreased cardiac output and elevated intracardiac filling pressure, cause gut epithelial hypoperfusion and dysfunction, which causes increased intestinal permeability, intestinal malabsorption, altered gut microbiota, and increased sodium and fluid reabsorption, thereby resulting in increased inflammation, cardiac cachexia, insulin resistance, and HF decompensation, respectively.

Figure 2.. Proposed approaches to modulating gut microbiota in heart failure.

Figure 2 illustrates different approaches to modulation of the gut microbiota in heart failure. These include dietary, prebiotic and probiotic interventions, targeted non-lethal inhibition of enzymes within the gut microbiota, and fecal microbiota transplantation.