Bisphenol P triggers hepatic injury via gut microbiota dysbiosis-Induced intestinal barrier disruption.

Bisphenol P (BPP), a structural analog of bisphenol A (BPA), is increasingly found in industrial and consumer products. Despite its prevalence in food and biological samples, its health risks are largely uncharacterized. This study aimed to investigate whether BPP exposure induce liver injury through a disrupted gut-liver axis, specifically via gut microbiota dysbiosis and intestinal barrier damage in mice. Mice received an oral dose of 30 μg/kg bw/day of BPP for five weeks to simulate typical dietary exposure. Four groups were included: Control group, BPP group, antibiotics (ABX) group and ABX + BPP group. The results revealed that BPP exposure significantly altered gut microbiota composition, increased intestinal permeability, and elevated serum lipopolysaccharide (LPS) levels, which activated the hepatic LPS/Toll-like receptor 4 (TLR4) pathway. This resulted in liver inflammation, oxidative stress, lipid metabolism disruption, and fibrosis. Importantly, antibiotic treatment, which depleted the gut microbiota, alleviated these effects, highlighting the crucial role of the gut-liver axis in mediating BPP toxicity. Our findings suggest that BPP exposure is associated with gut microbiota dysbiosis and intestinal barrier impairment, which may contribute to hepatic injury via the gut-liver axis. This provides critical insights into the health risks of BPP and highlights the role of the gut microbiota in chemical toxicity. These findings are vital for future safety assessments of bisphenol substitutes and suggest potential therapeutic targets in gut microbiota.