Environmental endocrine disrupting chemical-DEHP exposure-provoked biotoxicity about microbiota-gut-mammary axis in lactating mice via multi-omics technologies

Abstract

• 16SrRNA sequencing, metabolome, and transcriptomic reveal DEHP toxicity in Lactating Female. • DEHP/MEHP induces colon flora disturbance, accompanied by colon inflammation, which ultimately leads to mammary gland damage. • Inhibition of ERK1/2 pathway in mammary epithelial cells leads to cell apoptosis and ferroptosis, resulting in abnormal milk fat metabolism. Plastics, pervasive in humans and nature, often contain Di (2-ethylhexyl) phthalate (DEHP) that enhance plastic’s elasticity. However, DEHP is an environmental endocrine disruptor, affecting organisms upon exposure. Understanding mammary gland development in lactating females is crucial for offspring nourishment and dairy production. Employing multi-omics technology, this study aimed to uncover DEHP’s impact on the microbial–gut–mammary axis. Forty mice were exposed to varying DEHP doses for 18 d. We performed 16S sequencing, metabolomics, mammary tissue observation, and gene expression profiling. Results revealed DEHP’s influence on microbial diversity, with increased Lactobacillus abundance and reduced Proteobacteria , alongside colonic inflammation. Elevated GMP and adenosine 5′-monophosphate levels in the bloodstream were noted, while ascorbic acid, glycitein, and others decreased. MEHP, a DEHP metabolite, damaged mammary tissues, inhibiting ERK1/2 phosphorylation, triggering apoptosis and ferroptosis. These findings unveil potential therapeutic targets for DEHP-induced chronic toxicity in humans and animals, aiding dairy livestock health and human well-being. This study underscores the importance of understanding the adverse effects of DEHP exposure on mammalian systems.