Short-Chain Fatty Acids in Gut–Heart Axis: Their Role in the Pathology of Heart Failure

Abstract

Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Accumulating evidence has implicated the possible contribution of gut microbiota-derived metabolites, short-chain fatty acids (SCFAs), on the pathology of a variety of diseases. The changes of SCFA concentration were reported to be observed in various cardiovascular diseases including HF in experimental animals and humans. HF causes hypoperfusion and/or congestion in the gut, which may lead to lowered production of SCFAs, possibly through the pathological changes of the gut microenvironment including microbiota composition. Recent studies suggest that SCFAs may play a significant role in the pathology of HF, possibly through an agonistic effect on G-protein-coupled receptors, histone deacetylases (HDACs) inhibition, restoration of mitochondrial function, amelioration of cardiac inflammatory response, its utilization as an energy source, and remote effect attributable to a protective effect on the other organs. Collectively, in the pathology of HF, SCFAs might play a significant role as a key mediator in the gut–heart axis. However, these possible mechanisms have not been entirely clarified and need further investigation.

Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells

“…This suggests that butyrate supplementation might have potential beneficial effects on kidney function, as it has been illustrated in several animal studies [46][47][48]. Besides helping to preserve kidney function, SCFAs seem to be beneficial for the whole cardiovascular system, by showing anti-hypertensive effects [49] and protecting from atherosclerosis [50] and heart failure [51]. Interestingly, the benefits of butyrate also go beyond the cardiovascular system, as they have been observed for instance acting on the central nervous system [52] and on intestinal barrier integrity [53,54].…”

De Novo Metabolic Syndrome 1 Year after Liver Transplantation and Its Association with Mid- and Long-Term Morbidity and Mortality in Liver Recipients

“…Although no statistically significant differences were noted between kidney function in patients with and without MS 1 year after transplantation, patients in the former group fared worse in terms of renal parameters. Given the underlying pathophysiological mechanisms of MS-induced renal injury, it is likely that these initially insignificant findings deteriorated over the course of follow-up and along with the increasing number of MS components ultimately contributed to increased CV morbidity and mortality secondary to accelerated loss of renal function [ 29 ].…”

Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease

“…The loss of anti-inflammatory SCFAs could be a direct driver of inflammation and especially gastrointestinal damage in CD [118]. Furthermore, loss of SCFA production could directly contribute to cardiac CD pathogenesis: SCFAs prevent mitochondrial damage and reactive oxygen species production and serve as an alternative cardiac fuel source [122]. However, it should be noted that these were metagenomic rather than metatranscriptomic or metaproteomic studies.…”