Simple SummaryThe aim of this study was to investigate the effect of puerarin supplementation on the growth performance and intestinal function of piglets challenged with enterotoxigenicEscherichia coli(ETEC) K88, which provided a theoretical basis for its practical application as a new feed additive. Dietary supplementation with 5 mg/kg puerarin alleviated intestinal injury and improved the intestinal function of piglets challenged with ETEC K88 by increasing the number ofBifidobacteriumin the colon andLactobacillusin the jejunum, cecum and colon; decreasing the number ofEscherichia coliin the jejunum and cecum; reducing the hydrogen peroxide content in the jejunum and myeloperoxidase activity in the jejunum and ileum; and increasing the activities of catalase and superoxide dismutase in the jejunum and ileum. These results provide important insights into the development of an effective treatment for ETEC K88 infection and other enteric diseases.AbstractThe objective of this study was to investigate the effect of puerarin supplementation on the growth performance and intestinal function of piglets challenged with enterotoxigenicEscherichia coli(ETEC) K88. Twenty-four ternary crossbred piglets were randomly assigned to three treatment groups: control group, ETEC group (challenged with ETEC K88 on day 8), and ETEC + Puerarin group (supplemented with 5 mg/kg puerarin and challenged with ETEC K88 on day 8). All piglets were orally administered D-xylose (0.1 g/kg body weight) on day 10, and blood samples were collected after 1 h. Subsequently, piglets were killed and intestinal samples were collected for further analysis. The results showed that puerarin supplementation significantly decreased the adverse effects of ETEC K88-challenged piglets; significantly improved growth performance; increased the number ofBifidobacteriumin the colon andLactobacillusin the jejunum, cecum and colon; decreased the number ofEscherichia coliin the jejunum and cecum; reduced the hydrogen peroxide content in the jejunum and myeloperoxidase activity in the jejunum and ileum; and increased the activities of catalase and superoxide dismutase in the jejunum and ileum. In addition, puerarin supplementation alleviated ETEC K88-induced intestinal injury in piglets, significantly downregulated the mRNA level of Interleukin-1β and upregulated the mRNA levels of intercellular cell adhesion molecule-1, myxovirus resistance protein 1, myxovirus resistance protein 2, and guanylate-binding protein-1 in the small intestine of piglets. In conclusion, dietary supplementation with puerarin could attenuate ETEC K88-induced intestinal injury by increasing the antioxidant and anti-inflammatory capacity and the number of beneficial intestinal bacteria in piglets.