Di(2-ethylhexyl) phthalate exposure disrupts intestinal microbiota and activates immune signaling pathways in zebrafish intestine

Di(2-ethylhexyl) phthalate (DEHP), a common plasticizer, exhibits environmental persistence and multisystem toxicity. With plastic production continually rising, China’s annual output exceeded 77 million tons in 2024, reflecting a 2.9% year-on-year increase (Ministry of Industry and Information Technology). This reflects large-scale consumption and increasing environmental pressure. However, its toxic mechanisms on the intestine, a key organ for defense and metabolism, remain poorly understood. This study indicate that DEHP exposure causes damage to zebrafish intestinal tissue, resulting in a reduction in commensal bacteria such as Fusobacterium and Cetobacterium , and enrichment of Allorhizobium–Neorhizobium–Pararhizobium–Rhizobium and Pseudomona . The analysis suggested that the expression of Toll-like receptor pathways, NOD-like receptor signaling pathways, and MAPK signaling pathways related to immunity and metabolism was upregulated. In addition,genes such as tlr4 , myd88 , nf-κb , and il10 were significantly upregulated. Together, these findings show that DEHP may raises the risk of intestinal immune injury via the TLR4/Myd88/NF-κB pathway and dysbiosis of the intestinal microbiota. This study contributes to the assessment and control of health risks associated with DEHP contamination in water. • DEHP increased vacuolization and damaged villus structure in zebrafish intestinal. • DEHP reduced Fusobacterium and enriched Pseudomonas in the intestinal microbiota. • DEHP triggered multiple immune signaling pathways including TLR4/MYD88/NF-κB. • Multi-omics integration uncovered DEHP-induced intestinal inflammation mechanism.