LAUSR

(1) Background: Deoxynivalenol (DON) is a general mycotoxin that induces severe intestinal barrier injury in humans and animals. Resveratrol (RES) efficiently exerts anti-inflammatory and antioxidant effects. However, the information regarding RES protecting against DON-induced oxidative stress and intestinal inflammation in piglets is limited. (2) Methods: A total of 64 weaned piglets (Duroc × (Landrace × Yorkshire), 21-d-old, barrow) were randomly allocated to four groups (eight replicate pens per group, each pen containing two piglets) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design. (3) Compared with unsupplemented DON-challenged piglets, RES supplementation in DON-challenged piglets increased ileal villus height and the abundance of ileal SOD1, GCLC and PG1-5 transcripts and Muc2 protein (p < 0.05), while decreasing the mRNA and proteins expression of ileal IL-1β, IL-6 and TNF-α, and malondialdehyde (MDA) levels in plasma and ileum in DON-challenged piglets (p < 0.05). Moreover, the abundances of class Bacilli, order Lactobacillales, family Lactobacillaceae and species Lactobacillus gasseri were increased in DON-challenged piglets fed a RES-supplemented diet compared with those in DON-challenged piglets(p ≤ 0.05). (4) Conclusions: our results indicated that RES supplementation in DON-challenged piglets efficiently attenuated intestinal inflammation and oxidative stress and improved gut microbiota, thereby alleviating DON-induced intestinal barrier injury.