Interplay Between Gut Microbiota and Amino Acid Metabolism in Heart Failure

Abstract

Heart failure (HF) is a complex clinical syndrome of which the incidence is on the rise worldwide. Cardiometabolic disorders are associated with the deterioration of cardiac function and progression of HF. Recently, there has been renewed interest in gut microbiota (GM) and its metabolites in the cardiovascular disease. HF-caused hypoperfusion could increase intestinal permeability, and a “leaky” bowel leads to bacterial translocation and make its metabolites more easily enter the circulation. Considerable evidence shows that the composition of microbiota and amino acids (AAs) has been altered in HF patients, and AAs could serve as a diagnostic and prognostic biomarker in HF. The findings indicate that the gut–amino acid–HF axis may play a key role in the progression of HF. In this paper, we focus on the interrelationship between the AA metabolism and GM alterations during the development of heart failure. We also discuss the potential prognostic and therapeutic value of the gut–amino acid–HF axis in the cortex of HF.

Interactions between the gut microbiome, associated metabolites and the manifestation and progression of heart failure with preserved ejection fraction in ZSF1 rats

“…Moreover, betadiversity, a measure of between sample similarity, revealed distinct groupings within the various microbiome landscapes, even at the initial stages of HFpEF manifestation. Generally, a decrease in microbiome diversity has been a de ning parameter of dysbiosis in several cardiometabolic and in ammatory diseases [6,17,39]. Speci cally, humans with HFpEF have also been shown to have diminished microbiome diversity [40,41] but it remains to be elucidated whether this is a trigger of HFpEF or collateral damage [13].…”

“…Thus, alterations in microbiome diversity may initially trigger the development of HFpEF and after onset of the disease intestinal damage might be accelerated in a vicious cycle. In this context, the gastrointestinal microbiome has emerged as an exceptionally modi able organ that could be the target of low-effort, noninvasive and low-cost interventions [39]. TMA and thus TMAO level can be in uenced by limitation of carnitine and cholin, found highly concentrated in foods from animal origin like meat and dairy products, and representing main sources for bacterial TMA production [14].…”

The Implication of the Gut Microbiome in Heart Failure

“…These metabolites can be considered as biomarkers of intestinal dysbiosis and can predict inflammation in patients known with HF [ 101 ]. These patients with elevated plasma levels of phenylalanine display increased levels of inflammatory cytokines (IL-8, IL-10), C-reactive protein (CRP) and associate higher mortality [ 102 ], whereas glycine manifest anti-inflammatory effects and seem to offer protection to the cells and heart [ 103 ]. Furthermore, in an analysis of data gathered from the FINRISK and PROSPER cohorts, phenylalanine was reported to be an independent predictor of HF [ 104 ].…”

Identification of the metabolic state of surviving cardiomyocytes in the human infarcted heart by spatial single-cell transcriptomics

“…4. Amino acids are used as metabolic substrates in the ischemic heart [9] , and also as diagnostic and prognostic markers for heart failure [10] . Our analysis suggests that multiple amino acid metabolic pathways, including "alanine, aspartate, glutamate, cysteine, methionine, glutathione, arginine, tyrosine, and tryptophan metabolism," were significantly downregulated in CM from infarcted hearts when compared to control hearts.…”