Weaning stress induces pigs oxidative stress, which decreases growth performance, causes intestinal damage, and increases diarrhea and death in piglets. Microbe-derived antioxidants (MA) have an antioxidant and immune-modulatory role, but the impacts of MA on growth performance, intestinal oxidative stress, structure and function, and inflammatory response of weaned piglets are unclear. To elucidate whether MA can modulate intestinal oxidative stress, inflammatory response, and barrier function impairment and the possible mechanisms of its modulation, a total of 60 DLY (a crossbreed of Duroc, Landrance, and Yorkshire) piglets were randomly selected from 6 litters, with 10 piglets from each litter. Piglets from the same litter with similar body weight (6.44 ± 0.08 kg) were assigned to two groups: MA group (MA) and control group (Con). Results indicated that MA treatment markedly increased (p < 0.01) the average daily gain and average feed intake while decreasing the F/G (feed conversion ratio) (p < 0.01) at days 21-41. The addition of MA noticeably inhibited the ROS-NLRP3-IL-1β pathway (p < 0.05) and decreased inflammatory factors such as IL-1β and IL-18 in the intestine (p < 0.01). Moreover, MA supplementation significantly reduced the jejunal myosin light-chain kinase content (p < 0.01) while increasing the jejunal ZO-1 and Occludin content (p < 0.05). MA supplementation resulted in a noticeable rise in the colonic CD206 positive cells (p < 0.01) and mRNA expression of iNOS (p < 0.01), COX2 (p < 0.05), TLR4 (p < 0.01), MyD88 (p < 0.01), and NF-κB (p < 0.01). MA treatment also activated the Nrf2-HO-1 pathway (p < 0.01). These discoveries imply that MA can improve the antioxidant capacity by activating the Nrf2 pathway, alleviate intestinal inflammation by inhibiting the activation of the ROS-NLRP3-IL-1β pathway and regulating the polarization of intestinal macrophages, and ultimately improve the growth performance of weaned piglets.
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