Elucidating the beneficial effects of gut microbiota-derived metabolites in treating hepatocellular carcinoma: an integrated network pharmacology, molecular docking, and single-cell sequencing analysis
In silico study uncovers multi-target inhibition of hepatocellular carcinoma by gut microbiota metabolites, highlighting 3-indolepropionic acid as a promising therapeutic candidate.
Key Points
To elucidate the molecular mechanisms and identify therapeutic targets through which gut microbiota-derived metabolites inhibit hepatocellular carcinoma.
Retrieved gut microbiota metabolites and their predicted targets to construct protein-protein interaction and microbiota-metabolite-target-disease networks intersecting with hepatocellular carcinoma targets.
Evaluated the prognostic relevance and tumor microenvironment distribution of core genes using public transcriptomic databases and single-cell RNA sequencing data.
Assessed pharmacokinetic and safety properties of candidate metabolites and validated binding affinities against core targets using molecular docking.
Identified eight core target genes (AKT1, IL6, PPARG, IL1B, JUN, NFKB1, CASP3, and PTGS2) regulated by seven primary microbial metabolites.
Single-cell RNA sequencing revealed that the expression profiles of core target genes strongly correlated with the cellular landscape of the hepatocellular carcinoma tumor microenvironment.
Molecular docking demonstrated that 3-indolepropionic acid exhibited the highest binding affinity to the identified core therapeutic targets.