The Role of Gut Microbiota in Heart Failure: When Friends Become Enemies

Abstract

Heart failure is a complex health issue, with important consequences on the overall wellbeing of patients. It can occur both in acute and chronic forms and, in the latter, the immune system appears to play an important role in the pathogenesis of the disease. In particular, in the forms with preserved ejection fraction or with only mildly reduced ejection fraction, some specific associations with chronic inflammatory diseases have been observed. Another interesting aspect that is worth considering is the role of microbiota modulation, in this context: given the importance of microbiota in the modulation of immune responses, it is possible that changes in its composition may somewhat influence the progression and even the pathogenesis of heart failure. In this narrative review, we aim to examine the relationship between immunity and heart failure, with a special focus on the role of microbiota in this pathological condition.

Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability

“…There is evidence in the literature that the dysbiosis of the gut microbiota is associated with high circulating TMAO concentrations due to a disrupted gut mucosal barrier and increased intestinal permeability [22,34]. TMAO activates signaling pathways such as TGF-β1/Smad3 and p65 NF-κB, leading to a decrease in energy metabolism and mitochondrial function, and impairs the tricarboxylic acid (TCA) cycle, ultimately adversely affecting myocardial contractile function and intracellular calcium processing, and consequently triggering cardiac hypertrophy and myocardial fibrosis [1,20,22].…”

“…According to the current pathogenetic aspects of chronic heart failure (HF), systemic inflammation plays a central role in the progression of the disease [1]. HF with reduced ejection fraction (HFrEF) leads to intestinal congestion, which subsequently impairs the integrity and function of the intestinal epithelial barrier and increases intestinal permeability [2].…”

Anti-Inflammatory, Antioxidant, Metabolic and Gut Microbiota Modulation Activities of Probiotic in Cardiac Remodeling Condition: Evidence from Systematic Study and Meta-Analysis of Randomized Controlled Trials

“…Dysbiosis is a condition in which there is an alteration of the gut microbiota [ 7 ], and this condition is suspected of causing elevated levels of reactive oxygen species, lipopolysaccharides (LPSs), and harmful metabolites that can lead to cardiac hypertrophy, fibrosis, and an increase in proinflammatory cytokines, which are the primary risk factors of cardiovascular disease (CVD) [ 8 ]. According to recent investigations, probiotics offer a promising therapy to reduce inflammation, permeability, and translocation of LPSs and harmful metabolites into circulation, and oxidative stress, thereby reducing cardiac hypertrophy and contractile dysfunction in HF patients [ 9 , 10 ]. In addition to reducing risk factors for cardiovascular disease, probiotics have the potential to increase patient QoL because probiotics can boost skeletal muscle mass [ 11 ].…”