Integorated multi-omics reveals the NOS2-metabolite-microbiota regulatory axis underlying feed efficiency in laying hens.

Feed efficiency (Feed conversion ratio, FCR), a critical economic indicator for poultry breeding, is closely associated with the sustainable advancement of the poultry production. However, the molecular mechanisms governing differences in FCR among chickens have not yet been fully elucidated. Transcriptome analysis identified 189 differentially expressed genes, among which NOS2 was identified as a key gene significantly involved in the arginine biosynthesis pathway. Following NOS2 interference for 48 h in primary hepatocytes, CAT, Nrf2, FASN were downregulated, while overexpressed NOS2 showed an opposite tendency. Metabolomics analysis identified 116 and 87 differential metabolites in the liver and cecum contents, respectively. Metagenomics analysis identified s__Methanocorpusculum_vombati as the dominant taxa for LFCR. Integrated analysis revealed that NOS2 expression was positively correlated with 23 liver metabolites. Combined analysis found that genus Oscillibacter as a central hub microbiota, significantly connecting to 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid in the cecum content. This study elucidates the regulatory role of NOS2 to antioxidant, lipogenesis and inflammatory of chicken hepatocyte, and predicted that NOS2 gene as a central regulator to improve feed efficiency in laying hens.