How copper can impact pig growth: comparing the effect of copper sulfate and monovalent copper oxide on oxidative status, inflammation, gene abundance, and microbial modulation as potential mechanisms of action

The beneficial effect of elevated concentrations of copper (Cu) on growth performance of pigs has been already demonstrated; however, their mechanism of action is not fully discovered. The objective of the present experiment was to investigate the effects of including Cu from copper sulfate (CuSO(4)) or monovalent copper oxide (Cu(2)O) in the diet of growing pigs on oxidative stress, inflammation, gene abundance, and microbial modulation. We used 120 pigs with initial body weight (BW) of 11.5 ± 0.98 kg in 2 blocks of 60 pigs, 3 dietary treatments, 5 pigs per pen, and 4 replicate pens per treatment within each block for a total of 8 pens per treatment. Dietary treatments included the negative control (NC) diet containing 20 mg Cu/kg and 2 diets in which 250 mg Cu/kg from CuSO(4) or Cu(2)O was added to the NC. On day 28, serum samples were collected from one pig per pen and this pig was then euthanized to obtain liver samples for the analysis of oxidative stress markers (Cu/Zn superoxide dismutase, glutathione peroxidase, and malondialdehyde, MDA). Serum samples were analyzed for cytokines. Jejunum tissue and colon content were collected and used for transcriptomic analyses and microbial characterization, respectively. Results indicated that there were greater (P < 0.05) MDA levels in the liver of pigs fed the diet with 250 mg/kg CuSO(4) than in pigs fed the other diets. The serum concentration of tumor necrosis factor-alpha was greater (P < 0.05) in pigs fed diets containing CuSO(4) compared with pigs fed the NC diet or the diet with 250 mg Cu/kg from Cu(2)O. Pigs fed diets containing CuSO(4) or Cu(2)O had a greater (P < 0.05) abundance of genes related to the intestinal barrier function and nutrient transport, but a lower (P < 0.05) abundance of pro-inflammatory genes compared with pigs fed the NC diet. Supplementing diets with CuSO(4) or Cu(2)O also increased (P < 0.05) the abundance of Lachnospiraceae and Peptostreptococcaceae families and reduced (P < 0.05) the abundance of the Rikenellaceae family, Campylobacter, and Streptococcus genera in the colon of pigs. In conclusion, adding 250 mg/kg of Cu from CuSO(4) or Cu(2)O regulates genes abundance in charge of the immune system and growth, and promotes changes in the intestinal microbiota; however, Cu(2)O induces less systemic oxidation and inflammation compared with CuSO(4).