Prenatal benzo[a]pyrene exposure exacerbates OVA-induced asthma in offspring mice

Prenatal exposure to Benzo[a]pyrene (B[a]P) may increase asthma risk by altering immune responses and gut microbiota, but its role in exacerbating offspring asthma remains unclear. This study aimed to investigate the effect of prenatal B[a]P exposure on offspring asthma phenotype based on an ovalbumin (OVA)-induced asthma mice model and clarify the underlying mechanism. Pregnant C57BL/6 N mice were gavaged with B[a]P or vehicle during gestation. Offspring were divided into control, B[a]P, OVA, and B[a]P + OVA groups. Asthma was induced by OVA sensitization and challenge. Airway hyperresponsiveness (AHR), lung pathology, mucus production, immune organ indices, serum OVA-specific IgE, lung tissue levels of IL-17A, IL-5, IFN-γ, and TGF-β, and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were measured. Besides, gut microbiota profiles were analyzed by 16S rRNA sequencing and bioinformatics. Prenatal B[a]P exposure did not affect maternal food intake or body weight, but significantly reduced litter size. B[a]P exposure increased thymus and spleen weights, thymus index, Penh value, lung cytokine levels (IFN-γ, 1.40-fold increase; TGF-β, 1.31-fold increase), and counts of neutrophils (3.70-fold increase) and monocytes (3.71-fold increase) in BALF in OVA-sensitized offspring mice. Besides, B[a]P + OVA mice showed thicker airway walls, and higher mucus secretion and Muc5ac expression (Muc5ac mRNA: 1.99-fold increase; MUC5AC protein: 1.48-fold increase). Gut microbiota analysis revealed increase in alpha diversity and notable shifts in bacterial composition, especially in Clostridia_UCG-014 abundance (18.68-fold increase). Prenatal B[a]P exposure exacerbated OVA-induced asthma by enhancing airway inflammation, mucus secretion, and gut microbiota dysbiosis, highlighting early gut microbiota as a potential target for asthma risk prediction and intervention.