Glucuronolactone Restores the Intestinal Barrier and Redox Balance Partly Through the Nrf2/Akt/FOXO1 Pathway to Alleviate Weaning Stress-Induced Intestinal Dysfunction in Piglets

(1) Background: Glucuronolactone (GLU) is a glucose metabolite with antioxidant activity. At present, the exact role of it in regulating the intestinal health of piglets under weaning stress is not clear. The purpose of this study is to investigate the effects of GLU on the growth performance and intestinal health of piglets under weaning stress and to explore potential mechanisms. (2) Methods: Twenty-four weaned piglets were randomly assigned into two groups, with one group receiving a basal diet and the other group receiving an experimental diet supplemented with 200 mg/kg of GLU. (3) Results: GLU increased the ADG, ADFI, and final body weight of piglets, while reducing the diarrhea rate. Mechanistically, GLU alleviates weaning stress-induced intestinal oxidative stress and inflammatory responses in piglets partly through activating the Nrf2-Akt signaling pathway to suppress the transcriptional activity of FOXO1, while also inhibiting the activation of the TLR4-MAPK signaling pathway to reduce the secretion of pro-inflammatory cytokines. Moreover, GLU increased the relative abundance of <i>Lactobacillus reuteri</i> in the ileum of piglets and improved the composition of the gut microbiota. (4) Conclusions: GLU reduced inflammation and oxidative stress through the Nrf2/Akt/FOXO1 signaling pathway and improved intestinal health, resulting in improved growth performance of the piglets.