The combined effect of early-life Bisphenol A (BPA) exposure and post-weaning high-fat diet on the intestinal health of mice.

Exposure to bisphenol A (BPA) and long-term high-fat diet (HFD) have been proven to have adverse effects on human health. This study demonstrated that the sequential exposure to BPA in early life and high-fat diet after weaning jointly impaired intestinal health. We found that BPA altered the gut microbiota composition of offspring, reducing microbial diversity and increasing Proteobacteria abundance. While short-term HFD intake partially restored microbial diversity, prolonged HFD feeding exacerbated dysbiosis. Early-life BPA exposure and subsequent HFD synergistically increased intestinal permeability, elevated serum zonulin and endotoxin (ET), and induced colonic inflammation. Notably, serum ET levels were significantly influenced by sex. Transcriptomic analysis revealed that the T cell receptor (TCR) and cell adhesion molecule (CAMs) signaling pathways were the key pathways associated with intestinal barrier impairment. Immunohistochemical analysis further showed increased CD3+ T cell infiltration and ICAM-1 positive area in the colon of 13-week-old male offspring, particularly in the BPA + HFD group. These findings highlight a critical developmental window during which environmental and dietary factors interact to program long-term intestinal vulnerability.