The potential pathways underlying the association of propyl-paraben exposure with aeroallergen sensitization and EASI score using metabolomics analysis

Propyl-paraben exposure is associated with aeroallergen sensitization, but its association with atopic dermatitis (AD) is inconclusive. No studies have been conducted on the metabolomic pathways underlying these associations. We investigated the associations between propyl-paraben exposure and aeroallergen sensitization, AD, and Eczema Area and Severity Index (EASI) score and identified the underlying pathways using untargeted metabolomics analysis. We enrolled 455 children in a general population study. Skin prick tests were performed with the assessment of EASI score. Urinary propyl-, butyl-, ethyl-, and methyl-paraben levels were measured. Untargeted metabolomics analysis was performed on the first and fifth urine propyl-paraben quintile groups. The highest urine propyl-paraben quintile group was associated with aeroallergen sensitization, but not with AD. Glycine, threonine, serine, ornithine, isoleucine, arabinofuranose, d-lyxofuranose, citrate, and picolinic acid levels were higher, whereas palmitic acid and 2-palmitoylglycerol levels were lower in the highest quintile propyl-paraben group, than in the lowest quintile group. The propyl-paraben-induced metabolic perturbations were associated with serine and glycine metabolisms, branched-chain amino acid metabolism, and ammonia recycling. Propyl-paraben exposure was associated with aeroallergen sensitization and EASI score, partially via metabolomic changes related with oxidative stress, mTOR, peroxisome proliferator-activated receptors pathway, aryl hydrocarbon receptor signaling pathways, and tricarboxylic acid cycle.