Puerarin (PU), a natural bioactive isoflavone derived from the edible root of Pueraria lobata, exhibits multi-pharmacological activities, including antioxidant, lipid metabolism-regulating, and immunomodulatory properties. The decline in the reproductive performance of hens is primarily attributed to age-related dysbiosis of gut function and reduced function of the liver-ovary axis. However, the systemic mechanisms linking puerarin-induced microbiota changes to improvements in hepatic and ovarian function in aged hens remain poorly defined. In this study, we performed a multi-omics investigation to explore the effects on gut microbiota, liver metabolism, ovarian function, and the associations among them induced by dietary puerarin in aged hens. The results demonstrated that dietary supplementation with 200 mg/kg puerarin significantly improved egg quality, laying rate, and feed conversion efficiency, restored endocrine hormone homeostasis, and reduced ovarian oxidative stress and apoptosis. Puerarin stimulated carbon flux partitioning through the hepatic citrate cycle (TCA) and pentose phosphate pathway, thereby enhancing vitellogenin (VTG) synthesis and its transport to the ovary. Furthermore, puerarin activated the cytokine–cytokine receptor interaction pathway and reversed microbial dysbiosis (e.g., Lactobacillus and Bacteroides), thereby ameliorating intestinal functional decline. Significant correlations were also observed among hepatic tauroursodeoxycholic acid levels, intestinal expression of the lipid metabolism genes CD36 and GPAT3, and the relative abundance of Lactobacillus. Multi-omics analyses revealed that puerarin ameliorated age-related hepatic lipid metabolism disorders by targeted regulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the gut and liver. We elucidated the direct effects of puerarin-induced alterations in gut microbial abundance and reproductive performance in aging hens, highlighting the mediating role of liver function. These findings collectively indicate that puerarin positively redirected the gut–liver–ovary axis function to mitigate reproductive aging, suggesting potential to improve metabolic health in aging hens.
Huang et al. (2026) studied this question.