Cadmium chloride administered through drinking water disrupts the gut-liver axis through intestinal barrier failure, endoplasmic reticulum stress, and PIEZO1 signaling in broiler chickens

This experiment was designed to investigate the impact of cadmium chloride (CdCl₂) exposure on growth performance, intestinal barrier integrity, liver damage, endoplasmic reticulum stress (ER) , and mechanically sensitive Piezo-type mechanosensitive ion channel component 1 (PIEZO1) signaling in broiler chickens. Eighty Arbor Acres broiler chickens were randomly allocated into four experimental groups, and each group received different concentrations of CdCl₂ administered through drinking water (0 mg/L as the control, 20, 40, and 60 mg/L) from day 18 to day 35. Exposure to CdCl₂ resulted in a significant reduction in body weight gain and impaired leg bone mineralization in a dose-dependent manner. The results also demonstrated compromised intestinal barrier function, evidenced by a significant decrease in tight junction proteins including claudin-1, occludin, and zonula occludens-1 (ZO-1) levels, along with increased intestinal mucosal injury. Furthermore, CdCl₂ exposure altered the diversity and composition of the gut microbiota and significantly reduced serum immunoglobulin levels (IgA, IgG, and IgM) , indicating disruption of the gut microbiota–immune axis. CdCl₂ also significantly activated endoplasmic reticulum stress signaling, as evidenced by elevated expression levels of glucose-regulated protein 78 (GRP78) , protein kinase R-like endoplasmic reticulum kinase (PERK) , and C/EBP homologous protein (CHOP) . Notably, hepatic expression of the PIEZO1 gene was significantly upregulated following cadmium exposure. Taken together, these outcomes show that CdCl₂ exposure through drinking water disrupts intestinal, hepatic, and skeletal homeostasis through intestinal barrier dysfunction, gut microbial dysbiosis, immunosuppression, activation of endoplasmic reticulum stress pathways, and upregulation of Piezo1, thereby providing mechanistic insight into cadmium-induced toxicity in broiler chickens under poultry production conditions.