Lutein-Associated Crosstalk Between Hepatic Transcriptional Programs and Cecal Microbiota Is Linked to Antioxidant, Stress, and Immune Homeostasis in Laying Hens

Lutein is a dietary xanthophyll carotenoid with recognized antioxidant and immunomodulatory potential, yet the molecular basis underlying its nutritional effects in laying hens remains insufficiently understood. Here, liver transcriptomic profiling and 16S rRNA sequencing were combined to investigate the response of laying hens to dietary lutein supplementation. A total of 951 differentially expressed genes were identified in the liver, indicating marked transcriptional remodeling after lutein supplementation. Functional enrichment, gene set enrichment, and weighted gene co-expression network analyses consistently showed that these changes were mainly associated with metabolic regulation, redox/stress adaptation, and immune-related communication. In parallel, lutein supplementation changed cecal microbial community structure and shifted specific microbial biomarkers. Integrated correlation analyses further identified candidate host–microbiota association patterns, including a KLF2/FOXO3/Faecalibacterium axis and a KLF2/IL8L2/PrevotellaceaeGa6A1group axis. Overall, dietary lutein was associated with coordinated changes in the hepatic transcriptional profile and cecal microbial community structure, which converged on these two functional directions. These findings provide new insight into the nutritional effects of lutein in laying hens and identify candidate pathways and microbial nodes for future functional validation in poultry feeding systems.