A mechanistic study of bisphenol a exposure on asthma through integrating clinical research, network toxicology, machine learning, and multi-omics

Introduction BPA exposure is known to be correlated with asthma incidence. This study aimed to investigate the molecular mechanisms underlying bisphenol A (BPA)-induced asthma. Methods In this study, network toxicology, machine learning, and bioinformatics approaches were integrated with differential expression analysis across multiple datasets. Clinical validation was performed using serum BPA measurement, lung function tests, and quantitative PCR in peripheral blood mononuclear cells. Results BPA was significantly elevated in the serum of patients with asthma, showing negative correlations with lung function parameters, such as forced expiratory volume in one second (FEV1), the ratio of FEV1 to forced vital capacity (FEV1/FVC), maximal expiratory flow at 75% of FVC (MEF75), and maximal expiratory flow at 25% of FVC (MEF25), while displaying positive correlations with fractional exhaled nitric oxide, eosinophil count, and eosinophil percentage (p < 0.05). We identified 116 potential target genes associated with BPA-induced asthma, with significant enrichment in the JAK-STAT and Chemokine signaling pathways. Using machine learning and Cytoscape analysis, we further narrowed these to 10 core regulatory genes. BPA exhibits strong binding affinity for five target proteins (CCR3, IL2RB, IL2RA, CXCR4, and CCR7). Quantitative PCR in human peripheral blood mononuclear cells confirmed significant upregulation of the expression of corresponding genes (p < 0.05), with partial gene upregulation correlated with serum BPA levels. Discussion BPA exposure affects lung function and systemic immune-inflammatory responses in asthma, potentially modulating asthma pathogenesis by targeting specific genes and the JAK-STAT signaling pathway. These findings provide preliminary evidence for further exploration of the molecular mechanisms and potential therapeutic targets in BPA-induced asthma.