Key result
Gut microbiota metabolites stably bind core atrial fibrillation targets AKT1, IL6, and JUN in computational models.
Why the study?
Atrial fibrillation has complex pathogenesis and limited optimal treatments, motivating exploration of gut microbiota metabolites' protective effects and mechanisms.
In silico analysis suggests that specific gut microbiota metabolites may offer a protective effect against atrial fibrillation by regulating AKT1, IL6, and JUN pathways, providing promising lead molecules for future therapies.
May identify candidate metabolites for AF protection; leaves open whether these warrant experimental or clinical validation.
INTRODUCTION: Atrial Fibrillation (AF) is a prevalent arrhythmia with complex pathogenesis and limited optimal treatments. This study aims to explore the possible protective effects of gut microbiota metabolites against AF and the underlying mechanisms. METHODS: This study integrated network pharmacology, molecular docking, and molecular dynamics simulations to explore gut microbiota metabolites' role in AF. Metabolite targets were retrieved from gutMGene, Swiss Target Prediction, and SEA; AF-related genes from Gene- Cards, OMIM, and CTD. SwissADME and ADMETlab screened metabolites for drug-likeness and toxicity, while molecular docking and 100 ns molecular dynamics simulations verified the binding stability between metabolites and core target binding stability. RESULTS: A total of 22 intersecting targets were identified; protein-protein interaction analysis showed AKT1, IL6, and JUN as core hub genes. GO/KEGG enrichment indicated enrichment in oxidative stress, miRNA transcriptional regulation, PI3K-Akt, and MAPK pathways. Six safe metabolites (e.g., linoleic acid, hesperetin dihydrochalcone) were screened. Molecular docking confirmed their stable binding to core targets (naringenin chalcone-JUN and 5-(3,4- dihydroxyphenyl)-4-hydroxypentanoic acid-JUN had the strongest affinity), validated by 100 ns molecular dynamics simulations. CONCLUSION: Gut microbiota metabolites may regulate AF-related signaling pathways via AKT1, IL6, and JUN, supporting the gut-heart axis as an AF intervention framework. The six metabolites are promising lead molecules for gut-targeted AF therapy, pending further experimental validation.
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Ning et al. (2026) studied Atrial Fibrillation. Gut microbiota metabolites was evaluated on Binding stability to core targets. Gut microbiota metabolites demonstrated stable binding to core atrial fibrillation targets AKT1, IL6, and JUN in molecular docking and simulations, suggesting potential as therapeutic lead molecules.
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