Harnessing the gut microbiome for precision therapeutics in heart failure

Heart failure (HF) management remains challenging because patients often show large differences in how well treatments work and in how often adverse drug reactions occur. Traditional pharmacogenomics cannot fully explain these differences. Emerging evidence from pharmacomicrobiomics shows that the gut microbiome represents a previously underappreciated factor influencing drug responses. This review summarizes the two-way interactions between the gut microbiota and key HF drugs, including digoxin, angiotensin receptor-neprilysin inhibitors (ARNIs), ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRAs), and diuretics. On the one hand, gut microbes can change drug effects because they can metabolize drugs and affect host physiological pathways. On the other hand, HF drugs can change the structure and function of the gut microbial community. This review also discusses how microbiome-related features may serve as biomarkers to support personalized treatment and how strategies such as dietary changes and microbiota-targeted therapies may improve clinical outcomes. Although evidence remains limited, and certain methods require further refinement, integrating microbiome insights into HF treatment may support more precise and individualized treatment strategies and help address current therapeutic limitations.