The identification of metabolites from gut microbiota in HPV infection via network pharmacology.

Human papillomavirus (HPV) infection continues to pose a significant global health challenge. Although gut microbial metabolites have been associated with HPV infection, the mechanisms underlying this relationship remain inadequately understood. A network pharmacology approach was utilized to comprehensively explore the connections between gut microbial metabolites and HPV infection. Using gutMGene, GeneCards, OMIM and other databases, 43 key targets were identified as common elements between gut microbial metabolites and HPV infection. Protein-protein interaction network analysis further screened 10 core targets, including IL6, AKT1, IL1B, CASP3, NFKB1, EGFR, PPARG, JUN, PTGS2, and TLR4. Gene ontology (GO) enrichment analysis of these 43 key targets indicated their involvement in lipopolysaccharide response, oxidative stress, and inflammatory signaling. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the 10 core targets highlighted the TNF, Toll-like receptor, C-type lectin receptor, and IL-17 signaling pathways as the main enriched pathways. A comprehensive microbiota-metabolite-target-pathway network was constructed, illustrating that these core targets interact with 13 gut microbial metabolites, 97 gut microbes, and 10 key pathways. Among the 13 metabolites screened, succinate and short-chain fatty acids (acetate, butyrate, propionate) exhibited favorable drug-likeness and toxicological profiles, with succinate being the most notable. Molecular docking analysis indicated that succinate binds to IL1B with a binding energy of -5.66 kcal/mol, suggesting a potential interaction with this core inflammatory target. These results suggest that key gut microbial metabolites, particularly succinate, may influence HPV infection through immune-related pathways and potential interactions with IL1B. This study provides a new direction for understanding the relationship between microbial metabolites and HPV infection and offers a foundation for future investigations.