Mechanisms of gut microbiota metabolite-mediated gut-heart Axis in heart failure: An integrative study based on network pharmacology

Heart failure (HF) is a prevalent terminal-stage cardiovascular disease worldwide. Recent years have seen growing research on the gut-heart axis, yet the role of gut microbiota-derived metabolites in HF pathogenesis remains insufficiently explored.

This network pharmacology study screened overlapping targets of heart failure and gut metabolites via gutMGene, GeneCards and OMIM databases, then carried out PPI, enrichment, M-S-M-T network construction, as well as drug-likeness and toxicity prediction of metabolites.

We identified 47 candidate targets at the intersection of HF-related genes and gut metabolite-associated targets. PPI network analysis suggested that AKT1, TNF, TP53, IL6, and PPARG may represent key hub targets. Functional enrichment indicated potential associations with the NF-κB and PI3K-Akt signaling pathways. The M-S-M-T regulatory network results show that PPARG is the hub target with the most extensive connections. Drug-likeness and toxicity predictions suggested favorable in silico profiles for five metabolites, including 3-indolepropionic acid (IPA) and indole-3-lactic acid (ILA).

This network pharmacology study screened core genes, metabolites and pathways associated with the gut-heart axis in heart failure, providing hypothetical support for subsequent experimental research on intervening heart failure via gut microbiota-derived metabolites.