Multiple omics analysis reveals the potential modulation of oregano essential oil on oxidative stress and immune status of beef cattle

Oregano essential oil (OEO), known for its antioxidant and anti-inflammatory properties, shows promise as a natural immunomodulator in livestock. However, the underlying molecular mechanisms through which OEO influences immune health in ruminants are not yet fully understood. This study aimed to explore the molecular associations of OEO with oxidative stress and immune responses in beef cattle, using integrated transcriptomic and metabolomic analyses. Twenty-seven Pingliang red cattle (average weight: 270.47 ± 16.26 kg) were randomly assigned to three dietary groups: control (CON, basal diet), low-OEO (LOE, basal diet supplemented with 130 mg OEO/d), and high-OEO (HOE, basal diet supplemented with 260 mg OEO/d). Dietary OEO supplementation significantly increased levels of immunoglobulin G (IgG), immunoglobulin M (IgM), complement 3 (C3), and complement 4 (C4) in liver and muscle tissues ( P < 0.05 ). Additionally, it elevated the activities of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), catalase (CAT), and interleukin-4 (IL-4) in serum, liver, and muscle ( P < 0.05 ). Conversely, OEO supplementation significantly reduced levels of tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), malondialdehyde (MDA), adrenocorticotropic hormone (ACTH), and corticosterone (COR) in both serum and tissues ( P < 0.05 ). Transcriptomic analysis identified differentially expressed genes (e.g., COL6A4 , COL1A1 , COX) that were enriched in ECM-receptor interaction, PI3K-Akt signaling, and oxidative phosphorylation pathways. Metabolomic profiling revealed an upregulation of metabolites, including argininosuccinic acid, L-lysine, L-glutamate, and phosphocreatine, with significant enrichment in arginine and proline metabolism. Integrated multi-omics analysis further demonstrated co-enrichment in the pathways related to immune and antioxidant function, such as PI3K-Akt signaling. In conclusion, dietary OEO is associated with coordinated changes in oxidative stress/immune-related metabolism pathways. This integrated molecular response aligns with observed efficacy of OEO in mitigating stress and inflammation while supporting antioxidant function in beef cattle. These findings offer potential mechanistic insights into the role of OEO supplementation in promoting immune homeostasis and health in beef cattle.