Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure

Abstract

Objective: The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed.

Data sources: This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: "gut microbiota," "heart failure," "trimethylamine N-oxide (TMAO)," "short-chain fatty acid (SCFA)," "bile acid," "uremic toxin," "treatment," "diet," "probiotic," "prebiotic," "antibiotic," and "fecal microbiota transplantation."

Results: Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure.

Conclusions: The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.

Figure 1

Gut microbiota dysbiosis and bacterial translocation involved in the progression of heart failure. Decreased cardiac output leads to intestinal mucosal ischemia and/or edema, thus leading to a “leaky gut.” Bacterial translocation and systematic inflammation occur subsequently. Moreover, heart failure is accompanied by a shift of the gut microbiota composition as well as varied metabolic pathways, which exacerbate the disease. BA: Bile acid; FMT: Fecal microbiota transplantation; HF: Heart failure LPS: Lipopolysaccharide; MAMPs: Microbe-associated molecular patterns; NOD: Nucleotide oligomerization domain; SCFA: Short-chain fatty acid; TLRs: Toll-like receptors; TMA: Trimethylamine; TMAO: Trimethylamine N-oxide.

Figure 2

Pathways of trimethylamine N-oxide formation and its relationship with heart failure. TMA is formed through metabolization of choline and choline-containing compounds from diets by gut microbiota in the intestinal lumen. TMA can be absorbed from the intestine and delivered to the liver where FMO convert it to TMAO. It is found that TMAO is correlated with poor prognosis and severity of HF. BNP: B-type natriuretic peptide; FMO: Flavin-containing monooxygenase; HF: Heart failure; NT-proBNP: N-terminal pro-BNP; NYHA: New York Heart Association; TMA: Trimethylamine; TMAO: Trimethylamine N-oxide.

Figure 3

Roles of short-chain fatty acids involved in cardiovascular diseases. SCFAs are major products of microbial fermentation of dietary fibers. SCFAs mainly present cardioprotective effects, including modulating blood pressure, promoting post-infarction cardiac repair, anti-inflammation and maintaining gut barrier. Gpr41: G-protein-coupled receptor 41; Gpr43: G-protein-coupled receptor 43; HIF: Hypoxia-inducible factor; SCFA: Short-chain fatty acid; Treg: Regulatory T cell.