Gastrointestinal immunity and antioxidant defenses may be bolstered in young animals through prenatal immune system stimulation (PIS), but this is largely uninvestigated in swine. This study tested the hypothesis that PIS could regulate offspring's gastrointestinal immune response and oxidative stress profile. To this end, a PIS model was utilized in sows, delivering low-dose LPS during the final third of gestation to target the developing immune system. On day 78±1.8 of gestation, 14 Camborough sows (parity = 2.6±1.4) received either saline (CON) or LPS from O111:B4 (2.5 μg/kg of body weight). A subset of 34 weaned barrows (n=17 CON, PIS), weaned at 21±1.3 days, were anesthetized for subcutaneous temperature loggers and jugular catheter placement. Following recovery, all pigs received an intravenous injection of LPS (10 μg/kg body weight) from O111:B4. Our findings demonstrate that PIS enhances the gut immune response by upregulating key inflammatory cytokines, indicative of a proinflammatory profile. Consistently across the jejunum and ileum, SCF was modulated with heightened expression in PIS than CON ( 0.05). In the ileum alone, PIS exhibited heightened expression of proinflammatory cytokines and chemokines, including TNFα, IL-6, IL-1β, and CCL3L1, compared to CON ( 0.05). Exposure to PIS resulted in reduced systemic total antioxidant capacity (TAC) at hours 2-4 post-challenge ( 0.004). Piglets exposed to PIS had decreased jejunal tissue malondialdehyde (MDA) concentrations ( 0.049). Together, these data indicate that exposure to PIS alters the inflammatory profile of the GI immune response and oxidative status in weaned pigs.

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