Integrated transcriptomic and metabolomic analysis reveals key regulatory genes and pathways associated with feed...

Improving feed efficiency in Tianchang Sanhuang chickens is essential for reducing production costs and environmental burden. The objective of this study was to integrate transcriptomic and metabolomic analyses to identify key regulatory genes, metabolites, and pathways associated with residual feed intake (RFI) and feed efficiency. In this study, 650 Tianchang Sanhuang laying hens with similar body weights at 36 weeks of age were evaluated for daily feed intake (DFI), RFI, and feed conversion ratio (FCR). The chickens were classified by RFI (mean ± 0.5 SD) into high-RFI (HRFI, n = 165) and low-RFI (LRFI, n = 158) groups. Phenotypes, serum biochemistry, antioxidant indices, and intestinal traits were compared in subsets (n = 8 per group). Duodenal transcriptomes (RNA-seq) and serum metabolomes (LC-MS/MS) were profiled in independent subsets (n = 4 per group). Compared with HRFI, LRFI hens showed lower RFI, FCR, and DFI (P < 0.01), with no differences in expected feed intake (EFI), metabolic body weight (MBW), daily egg mass (DEM), or average daily gain (ADG) (P > 0.05). The LRFI group showed increased breast muscle redness (a)* (P < 0.05), higher leg muscle drip loss (P < 0.01), and significantly lower levels of triglycerides (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) (P < 0.05). The intestinal morphology and molecular analyses revealed enhanced nutrient absorption and intestinal barrier function in the LRFI group. Transcriptomic analysis identified 237 differentially expressed genes (P < 0.05, |log2FC| ≥ 1) enriched in pathways related to digestion, energy metabolism, and appetite regulation. Metabolomic analysis detected 101 differentially expressed metabolites (VIP ≥ 1, |log2FC| ≥ 1), indicating that RFI is closely associated with protein and lipid metabolism. Integrated analysis identified candidate biomarkers for low RFI individuals selection, including genes such as ACSM5, AHSG, CTRB1, PLA2G1B, AMY2A, CPA1, CCKAR and metabolites including taurine, uridine, L-phenylalanine, D-glucose 6-phosphate and 5‑hydroxy-L-tryptophan. Overall, LRFI hens maintain production while achieving lower intake, potentially via reduced inflammation/oxidative stress and enhanced digestion, barrier integrity, appetite, and energy metabolism, offering targets for marker-assisted improvement of feed efficiency in local breeds.