**Background:** Intrauterine growth retardation (IUGR) affects 15–20% of pig litters, causing oxidative damage, gut dysfunction, and reduced muscle growth that persists postnatally. Equol (Eq), a gut bacterial metabolite of daidzein, has potent antioxidant, anti-inflammatory, and estrogenic properties, but no prior study had tested its effects on IUGR piglets. This study aimed to evaluate whether dietary Eq supplementation could improve growth performance, redox status, intestinal health, and skeletal muscle development in weanling IUGR piglets.
**Methods:** Twenty newborn female IUGR piglets (mean BW 0.89 ± 0.06 kg) and ten NBW female piglets (mean BW 1.53 ± 0.09 kg) were selected from litters of third-to-fifth parity sows. After weaning at 21 d, NBW piglets received a basal diet (NBW group), 10 IUGR piglets received basal diet (IUGR group), and 10 IUGR piglets received basal diet + 50 mg Eq/kg diet (IUGR+Eq group) for 21 d. At trial end, serum, intestinal tissues (duodenum, jejunum, ileum), and longissimus thoracis (LT) muscle were collected. Outcomes included growth metrics, intestinal morphology (villus height, crypt depth, V/C), antioxidant markers (SOD, CAT, GSH-Px, T-AOC, MDA), serum barrier markers (DAO, D-lactate, endotoxin, immunoglobulins), cytokine concentrations (IFN-γ, TNF-α, IL-4, IL-10), mRNA expression of tight junction and mucin genes (ZO1, ZO2, CLDN1, CLDN2, OCLN, MUC1, MUC2, TFF3), and muscle fiber typing via ATPase staining and MyHC isoform mRNA.
**Key Results:** IUGR piglets had significantly lower final BW (9.53 vs 12.82 kg), ADG (181.56 vs 242.44 g/d), and ADFI (300.41 vs 398.27 g/d) than NBW piglets (all p<0.05). Eq supplementation significantly increased final BW (10.33 kg, +8.39%), ADG (208.07 g/d, +14.6%), and ADFI (345.48 g/d, +15%) in IUGR piglets (p<0.05). Intestinal morphology improved: duodenal crypt depth decreased (208.79 vs 263.32 μm, p=0.018), duodenal V/C increased (1.86 vs 1.39, p=0.006), and jejunal villus height increased (386.30 vs 322.58 μm, p=0.037). Antioxidant capacity improved: serum SOD (10.76 vs 7.45 U/mL, p=0.039) and CAT (16.45 vs 12.82 U/mL, p=0.029) increased; serum MDA decreased (2.45 vs 3.10 nmol/mL, p=0.043). Duodenal SOD (15.09 vs 10.80 U/mg prot, p=0.024) and CAT (8.58 vs 5.52 U/g prot, p=0.038) increased. Jejunal SOD increased (20.45 vs 13.87 U/mg prot, p=0.036) and MDA decreased (2.72 vs 3.58 nmol/mg prot, p=0.041). Ileal MDA decreased (3.46 vs 4.37 nmol/mg prot, p=0.032). Serum DAO activity (8.26 vs 10.23 U/L, p=0.025), D-lactate (25.28 vs 27.11 μg/mL, p=0.041), and endotoxin (160.30 vs 184.17 EU/mL, p=0.029) decreased, while IgG increased (6.82 vs 5.58 g/L, p=0.039). Jejunal TNF-α (59.12 vs 67.33 pg/mg prot, p=0.029) and IL-10 (26.05 vs 31.22 pg/mg prot, p=0.011) decreased; ileal TNF-α decreased (67.16 vs 79.67 pg/mg prot, p=0.008). mRNA expression of CLDN1, OCLN, and TFF3 increased in jejunum; ZO1, CLDN1, OCLN, and MUC2 increased in ileum (all p<0.05). Fast-fiber percentage in LT muscle increased, with higher MyHC IIb mRNA and lower MyHC I mRNA (p<0.05).
**Clinical Implications:** This is the first study to demonstrate that dietary equol supplementation at 50 mg/kg can partially reverse IUGR-induced growth retardation in weanling piglets. The mechanisms involve enhanced antioxidant capacity (increased SOD, CAT; reduced MDA), improved intestinal morphology and barrier integrity (reduced DAO, D-lactate, endotoxin; increased tight junction and mucin gene expression), reduced intestinal inflammation (lower TNF-α, IL-10), and promotion of fast-twitch muscle fiber development (increased MyHC IIb). These findings support Eq as a potential nutritional strategy to improve growth outcomes in IUGR piglets, which could reduce economic losses in swine production. Further research is needed to confirm these effects in larger-scale production settings and to explore the molecular mechanisms underlying Eq's actions.