Multi-omics reveals the mechanisms of DEHP driven pulmonary toxicity in ovalbumin-sensitized mice

Abstract

The plasticizer di- (2-ethylhexyl) phthalate (DEHP) is considered a risk factor for allergic diseases and has attracted public attention for its adverse effects on health. However, respiratory adverse effects after DEHP exposure in food allergies have rarely been reported. MiRNAs are considered to be key regulators in the complex interrelationships between the host and microbiome and may be a potential factor involved in DEHP-induced pulmonary toxicity. To investigate the adverse effects of DEHP on the lung during sensitization, we established an ovalbumin (OVA)-sensitized mouse model exposed to DEHP and performed 16S rDNA gene sequencing, miRNA sequencing, and correlation analysis. Our results showed that DEHP aggravated the immune disorder in OVA-sensitized mice, which was mainly characterized by an increase in the proportion of Th2 lymphocytes, and further enhanced OVA-induced airway inflammation without promoting pulmonary fibrosis. Compared with the OVA group, DEHP interfered with the lung microbial community, making Proteobacteria the dominant phylum, while Bacteroidetes were significantly reduced. Differentially expressed miRNAs were enriched in the PI3K/AKT pathway, which was closely related to immune function and airway inflammation. The expression of miR-146b-5p was elevated in the DEHP group, which was positively correlated with the proportion of Th2 cells and significantly negatively correlated with the abundance of Bacteroidetes. The results indicate that DEHP may interfere with the expression of miR-146b-5p, affect the composition of the lung microbiota, induce an imbalance in T cells, and lead to immune disorders and airway inflammation. The current study uses multi-omics to reveal the potential link between the plasticizer DEHP and allergic diseases and provides new insights into the ecotoxicology of environmental exposures to DEHP.