Table 3 Function and role of GM-derived metabolites on HF

SCFAs

Anti-inflammatory properties

Reduced SCFA levels linked to HF progression

[71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86]

ROS suppression

Potential reduction in cardiac hypertrophy and fibrosis through HDAC inhibition

Restoration of mitochondrial function

May enhance cardiac function via improved glucose metabolism and lipid regulation

Regulation of blood pressure (vasodilation, modulation of renin-angiotensin system)

Energy source for the heart

HDAC inhibition

Modulation of TET enzymes

TMAO

Activates Smad3 signaling pathways

TMAO levels increased in chronic HF patients, linked to HF progression

[87,88,89,90,91,92,93,94,95,96,97,98,99]

Increases pro-inflammatory cytokines (e.g., via NF-κB pathway)

Predictive marker for HF severity and poor prognosis

Induces mitochondrial ROS accumulation by inhibiting SIRT3 and SOD2

Associated with myocardial hypertrophy and fibrosis

Modifies DNA methylation (affects methyl-donor availability)

Disrupts cardiac energy metabolism and mitochondrial function

Chromatin remodeling (e.g., H3K4me3 upregulation)

Bile Acids

Regulates lipid and glucose metabolism (e.g., through FXR, TGR5)

Increased secondary-to-primary BA ratio in HF

[76, 100,101,102,103,104,105,106,107]

Modulates mitochondrial function

Linked to atrial fibrillation in HF patients

Regulates inflammation (e.g., via pro- and anti-inflammatory pathways)

Dysregulated BA signaling may impair lipid and energy metabolism with effect on cardiac stress