Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice

Bisphenol A (BPA) and diisobutyl (DIBP) phthalate are widely used as typical plasticizers in food packaging. Plasticizers can be released from polymers, migrate into food, and be ingested by humans, leading to various health problems. However, little research has investigated the combined toxicity of BPA and DIBP, particularly their intestinal toxicity. Our goal is to analyse the combined toxicity of BPA (50 mg/kg) and DIBP (500 mg/kg) on the intestines of KM mice. Additionally, we tried to find natural products that can inhibit or prevent the combined toxicity of BPA and DIBP. The results indicated that the combination of BPA and DIBP exposure resulted in a reduction of beneficial flora, an increase in D-Lac levels (136 ± 14 μmol/L), an increase in intestinal permeability, activation of the notch pathway, and a decline in intestinal stem cells (ISCs) to goblet cells, compared to single-exposure sources. Nevertheless,Rubus chingiiHu phenolic extract (RHPE) (200, 400 and 600 mg/kg) ameliorated the BPA and DIBP-induced intestinal microbiota disruption and intestinal mucosal barrier impairment by inhibiting the overactivation of the notch pathway. The results of this study highlight the potential risks to human health posed by the combination of BPA and DIBP and may help explain the potential pathways of enterotoxicity caused by combined ingestion.