Metabolic syndrome and a broken heart: trust your gut or risk your heart

Gut dysbiosis is increasingly recognized as a contributor to heart failure; however, its specific role in the development of metabolic syndrome-induced heart failure (MetS-HF) remains poorly defined. A defining feature of MetS-HF is cardiac steatosis, which drives lipotoxicity, maladaptive remodeling, and progressive cardiac dysfunction. This review integrates mechanistic and translational evidence showing how gut microbiota dysbiosis initiates and exacerbates MetS-HF by disrupting lipid homeostasis, leading to myocardial steatosis, metabolic remodeling, cardiomyocyte death, adverse structural remodeling, and impaired cardiac performance. We also highlight how gut dysbiosis promotes systemic inflammation and hypertension, further aggravating cardiac dysfunction in MetS-HF. Finally, we discuss the potential of artificial intelligence, integrative multiomics, and network-based bioinformatics to elucidate the molecular pathways linking gut dysbiosis to MetS-HF and to identify novel therapeutic targets.