Network toxicology of perfluorooctanoic acid-induced hepatointestinal injury and the protective effect of Lycium barbarum polysaccharides against perfluorooctanoic acid in broilers.

Given the extensive organ toxicity of perfluorooctanoic acid (PFOA), this study aimed to elucidate its mechanisms of hepatointestinal toxicity and to evaluate the protective efficacy of Lycium barbarum polysaccharides (LBP). In the initial phase, network toxicology and molecular docking were used to identify protein targets associated with PFOA-induced hepatointestinal toxicity. A total of 224 key protein targets were identified, which were mainly enriched in the PI3K-AKT signaling pathway. Based on these findings, an animal experiment was conducted. The study utilized 480 one-day-old male broilers which were randomly assigned to six groups, with each group containing eight replicates of ten chicks. The experimental period was from day 4 to day 42. The groups were as follows: Group C, blank control; Group P, 1.5 mg/L PFOA; Group D, 1.5 mg/L PFOA + 0.4% LBP; Group Z, 1.5 mg/L PFOA + 0.6% LBP; Group G, 1.5 mg/L PFOA + 0.8% LBP; Group L, 0.8% LBP only. The results showed that in comparison with group C, group P exhibited a significant decrease in ADG, ADFI levels, intestinal tight junction proteins expression, and activities of antioxidant enzymes. In contrast, pro-inflammatory cytokine levels were significantly increased. Supplementation with 0.8% LBP significantly ameliorated these adverse effects. Furthermore, PFOA exposure resulted in the inhibition of the PI3K-AKT pathway, while 0.8% LBP activated this pathway. To further understand the mechanisms of PFOA toxicity via the liver-intestine interactions, 16S rRNA sequencing was conducted, revealing that PFOA increased the abundances of Firmicutes and Campylobacterota while reducing Bacteroidota and Proteobacteria. The 0.8% LBP supplementation improved the microbiota composition by enhancing the diversity and abundance of beneficial bacteria, thereby conferring intestinal protection. These findings suggest that PFOA exposure can induce hepatointestinal toxicity, while LBP may serve as a feed additive to mitigate the adverse effects of PFOA. This study provides a novel approach for investigating PFOA toxicity and proposes innovative strategies for developing feed supplements to safeguard liver and intestinal health.