AbstractThe objective of this study was to investigate effects of zinc glycinate (ZnGly) supplementation reducing zinc oxide (ZnO) in feeds on intestinal health and growth of nursery pigs challenged with F18+Escherichia coli (E. coli).In total, 72 nursery pigs (BW 6.5 ± 0.5 kg) were allotted in a randomized complete block design to nine treatments: (1) NC: no challenge/no supplement; (2) PC:E. colichallenge/no-supplement; (3)E. colichallenge/ZnO at 2,500 mg/kg; (4, 5, and 6)E. colichallenge/ZnGly at 400, 800, and 1,200 mg/kg; and (7, 8, and 9)E. colichallenge/ZnGly at 400 mg/kg and ZnO at 700, 1,400, and 2,357 mg/kg. Pigs were fed for 28 d based on two phases (phase 1: 14 d and phase 2: 14 d). On day 7, challenged groups were orally inoculated with F18+E. coliat 6 × 109CFU/mL whereas NC received saline solution. The PC showed reduced ADG (P= 0.076) and G:F (P= 0.055) during phase 1 and increased fecal score (P< 0.05) during the first week of postchallenge when compared with NC, whereas supplementation of ZnGly from 0 to 1,200 mg/kg linearly increased (P =0.092) G:F and decreased (P <0.05) the fecal score of the pigs challenged with F18+E. coli. Supplementation of ZnGly from 0 to 1,200 mg/kg had quadratic effects on TNF-α (P =0.065; minimum 1.13 pg/mg at 850 mg/kg ZnGly), IL-8 (P =0.093; minimum 0.53 ng/mg at 494 mg/kg), and protein carbonyl (P =0.054; minimum 2.30 pg/mg at 675 mg/kg) and linearly increased mRNA expressions of ZIP4 (P =0.057) and ZnT5 (P =0.075) in the jejunum of the pigs. Supplementation of ZnGly from 0 to 1,200 mg/kg linearly increased (P <0.05) the relative abundance of Actinobacteria and had quadratic effects on Cyanobacteria (minimum 0.67% at 625 mg/kg ZnO) and Proteobacteria (maximum 45.6 g/d at 735 mg/kg) at the phylum level, with linearly decreased (P< 0.05)Enterobacteriaceaeat the family level in the jejunal mucosa-associated microbiota of the pigs. There was no difference in growth performance during the overall period, although pigs fed with ZnO at 2,500 mg/kg had greater (P <0.05) ADG than pigs fed with ZnGly at 400 mg/kg during the first week of the post challenge period. In conclusion, ZnGly could be an alternative to the pharmaceutical use of ZnO without negatively affecting the growth of nursery pigs by enhancing intestinal Zn absorption, reducing intestinal inflammation and oxidative stress, and providing positive changes in jejunal mucosa-associated microbiota.