Integrated Blood Transcriptome and Multi-Tissue Trace Mineral Analyses of Healthy Stocker Cattle Fed Complexed or Inorganic Trace Mineral Supplement

Supplementing trace minerals is common in managing bovine respiratory disease (BRD) in post-weaned cattle; however, its influence on host immunity and metabolism in high-risk cattle remains unclear. We aimed to assess the impact of three supplementation programs on liver and serum trace element concentrations and blood gene expression. Fifty-six high-risk beef steers were randomly assigned to one of three groups over 60 days: (1) sulfate-sourced Cu, Co, Mn, and Zn (INR), (2) amino acid-complexed Cu, Mn, Co, and Zn (AAC), or (3) AAC plus trace mineral and vitamin drench (COMBO). Serum and liver biopsies for Cu, Co, Mn, and Zn at d0, d28, and d60 were analyzed from cattle free of BRD (n = 9 INR; n = 6 AAC; n = 10 COMBO). Differences and correlations of mineral concentrations were analyzed via generalized linear mixed models and Spearman's rank coefficients, respectively (p < 0.05). Whole blood RNA samples from healthy cattle (n = 4 INR; n = 4 AAC; n = 4 COMBO) at d0, d13, d28, d45, and d60 were sequenced and analyzed for differentially expressed genes (DEGs) via glmmSeq (FDR < 0.05), edgeR (FDR < 0.10), and Trendy (p < 0.10). Serum and liver Cu and Co concentrations increased over time in all groups, with higher liver Cu in COMBO (487.985 μg/g) versus AAC (392.043 μg/g) at d60 (p = 0.013). Serum and liver Cu concentrations (ρ = 0.579, p = 6.59 × 10^-8) and serum and liver Co concentrations (ρ = 0.466, p = 2.80 × 10^-5) were linearly correlated. Minimal gene expression differences were found between AAC versus COMBO (n = 2 DEGs) and INR versus COMBO (n = 0 DEGs) over time. AAC versus INR revealed 107 DEGs (d13-d60) with increased traits in AAC including metabolism of carbohydrates/fat-soluble vitamins, antigen presentation, ATPase activity, and B- and T-cell activation, while osteoclast differentiation and neutrophil degranulation decreased in AAC compared to INR. Our study identifies gene expression differences in high-risk cattle fed inorganic or amino acid-complexed mineral supplements, revealing adaptive immune and metabolic mechanisms that may be improved by organically sourced supplementation.