Mult omics reveal the mechanism of solid dispersion of genistein in alleviating fatty liver hemorrhagic syndrome in laying hens.

Fatty Liver Hemorrhagic Syndrome (FLHS) is a metabolic disorder characterized by hepatic lipid metabolism dysfunction in poultry. This study aimed to investigate the efficacy and underlying mechanism of a solid dispersion of genistein (SDG) in ameliorating FLHS in laying hens. In this study, a total of 60 Lohmann gray laying hens, aged 40-week-old, were randomly divided into five groups including the control group (normal diet), MOD group (high-energy low-protein diet; HELP diet), GEN group (400 mg/kg GEN + HELP diet), SDG group (3200 mg/kg SDG + HELP diet), and physical mixture of GEN group (PMG) (3200 mg/kg PMG + HELP diet). The results demonstrated that all three treatment groups exerted therapeutic effects on FLHS, with SDG exhibiting the superior efficacy. SDG improved the production performance of laying hens, modulated hepatic function, and reduced blood lipid levels. Furthermore, SDG supplementation attenuated intestinal pathological damage and restored intestinal permeability and barrier function. Meanwhile, SDG reshaped gut microbiota structure and metabolite composition, increasing the abundance of Akkermansia, UCG-008, Elusimicrobium, Zag_111, and phosphoglycerides (P < 0.05), and reducing Bifidobacterium and lysophospholipids (P < 0.05). Transcriptomic analysis showed that the pyruvate metabolism pathway was significantly enriched. SDG upregulated the expression of PCK2, PC, and ACAT2 within this pathway, while downregulating the expression of ME1. The underlying mechanism may involve the inhibition of hepatic triglyceride synthesis, the facilitation of free cholesterol conversion into cholesterol esters, and the promotion of oxaloacetate and acetyl-CoA entry into the tricarboxylic acid cycle, thereby suppressing hepatic lipid deposition. In conclusion, our study demonstrated solid dispersion technology enhanced the effect of GEN on alleviating FLHS, and established a foundation for applying SDG to improving poultry liver health.