Network toxicology mechanisms of bisphenol a and bisphenol S from food contact materials in irritable bowel syndrome: evidence from molecular docking and dynamics simulation

Bisphenol A (BPA) and bisphenol S (BPS) are widely used in food packaging, yet their effects on irritable bowel syndrome (IBS), a functional gastrointestinal disorder affecting ~11% of the global population, remain unclear. This study investigated the potential effects of BPA and BPS on IBS and their molecular mechanisms through network toxicology and computational approaches. IBS-related targets and BPA/BPS action targets were retrieved from public databases, and overlapping targets were identified through Venn diagram analysis. Protein–protein interaction (PPI) network analysis was performed to identify core targets, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to evaluate binding affinity, and molecular dynamics simulations were conducted to validate binding stability. Enrichment analyses revealed that overlapping targets were mainly involved in peptidyl-serine phosphorylation, steroid hormone response, apoptosis, and NF-κB signaling pathway. All four core targets showed favorable binding with both bisphenols (binding energies < −5.0 kcal/mol), with PARP1 exhibiting the strongest binding (BPS: −8.6 kcal/mol; BPA: −7.6 kcal/mol). Molecular dynamics simulations confirmed stable complexes between PARP1/PTGS2 and both bisphenols, with stable RMSD and RMSF values. These results suggest that BPA and BPS may participate in IBS pathogenesis by modulating key targets including PARP1 and PTGS2, affecting inflammatory responses, oxidative stress, and apoptosis. These findings provide novel evidence for food safety assessment and highlight the need to address potential impacts of food contact materials on gastrointestinal health.