Mechanistic insights and ameliorative strategies: advances in DEHP-induced metabolic toxicity and intervention by natural bioactive compounds and probiotics

Di-(2-ethylhexyl) phthalate (DEHP) is a ubiquitous plasticizer and environmental contaminant linked to severe metabolic disorders. This review concisely elucidates the multi-organ mechanisms of DEHP-induced toxicity, highlighting its disruption of lipid, glucose, and protein homeostasis. Specifically, we delineate the crucial crosstalk between oxidative stress, endoplasmic reticulum (ER) stress, and inflammatory pathways that drive DEHP pathobiology. Furthermore, we systematically evaluate emerging ameliorative strategies, focusing on natural bioactive compounds and probiotics. We highlight how these interventions mitigate DEHP toxicity by targeting specific molecular hubs (e.g., PPARs, Nrf2) and restoring gut microbiota balance. By integrating mechanistic insights with natural interventions, this review provides a targeted framework for developing therapeutic countermeasures against phthalate-induced metabolic disruption.