"Microbial metabolites in cardioprotection: an immune-engineered framework for heart failure and post-ischemic...

The gut-heart axis is a new therapeutic target for cardiovascular diseases, which continue to be the leading cause of death worldwide. Metabolites originating from microorganisms have demonstrated significant impacts on inflammation, remodeling, and heart function.

By assessing molecular pathways, therapeutic options, and translational barriers, this narrative review seeks to objectively examine the cardioprotective potential of gut microbial metabolites.

We reviewed and summarized the most recent research on the impact of microbial metabolites, both beneficial and detrimental, on endothelium repair, fibrosis, immunometabolism, and cardiac bioenergetics. A systematic search was conducted using the phrases "gut-heart axis," "microbial metabolites," and "cardiovascular protection" in PubMed, Scopus, and Web of Science for the years 2018-2024. Preclinical and clinical research that met the eligibility requirements were vetted and narratively synthesized.

By modulating Nrf2, HDAC, and TGF-β/Smad, protective metabolites such as short-chain fatty acids, urolithins, and indoles have anti-inflammatory, anti-fibrotic, and mitochondrial-enhancing properties. On the other hand, oxidative stress and fibrosis are made worse by trimethylamine N-oxide and hydrogen sulfide. Postbiotic formulations, innovative delivery systems, and synthetic biology provide promising approaches for focused intervention. However, there are substantial translational obstacles due to pharmacokinetic, regulatory, and microbiota heterogeneity.

Microbial metabolites produced in the gut are a promising and revolutionary class of cardioprotectants. Future cardiovascular treatments may be redefined by precision-targeted gut-heart axis modulation, although clinical validation and regulatory standardization are still crucial.