Xiaotong Li, Deshuai Wang, Huiying Li, Jian Song, Hao Wang, Fengxia Liu, Sihuan Wang, Libo Zhang, Desheng Li, Jiali Wang, Yunhe Xu, Jun Wang, Shunshun Jin, Lizhi Jin, Donghui Shi
Dietary energy restriction typically impairs growth performance in broilers, whereas supplementation with an oregano essential oil-lauric acid complex (OEL) has been shown to improve feed efficiency under low‑energy conditions. However, the underlying mechanisms remain poorly understood. This study integrated serum untargeted metabolomics with cecal 16S rRNA sequencing to elucidate the energy‑sparing mechanism of OEL. A total of 600 one‑day‑old Arbor Acres broilers were randomly allocated to five dietary treatments, three of which were selected for multi‑omics analysis: a normal‑energy control (CON), a low‑energy control (LC, with a 210 kJ/kg reduction in metabolizable energy), and a low‑energy diet supplemented with 1000 mg/kg OEL (EXP). Serum metabolomics revealed that OEL profoundly reshaped the serum metabolome, yielding 238 differential metabolites (56 up‑regulated, 182 down‑regulated). Up‑regulated metabolites were enriched in aminoacyl‑tRNA biosynthesis, amino acid biosynthesis, and ABC transporter pathways, whereas down‑regulated metabolites were enriched in histidine metabolism, purine metabolism, and the mTOR and FoxO signaling pathways. Key differential metabolites included elevated tauroursodeoxycholic acid and L‑threonine, and decreased taurodeoxycholic acid, argininosuccinate, adenine, and S‑methyl‑5'‑thioadenosine. Cecal microbiota analysis showed that OEL enriched butyrate‑producing genera such as Lactobacillus, Ruminococcus, and Anaerostipes, while reducing opportunistic pathogens. PICRUSt2 functional prediction further indicated enhanced homolactic fermentation and short‑chain fatty acid synthesis pathways. Collectively, these findings suggest that OEL is associated with improved feed efficiency under energy restriction, which may be linked to a systematic remodeling of host amino acid, bile acid, and nucleotide metabolism, as well as a shift in gut microbiota composition toward butyrate‑producing bacteria and reduced opportunistic pathogens.