Neonatal enteral antibiotics reduce gut inflammation and delay systemic immune development in preterm pigs

Background: Antibiotics are frequently administered to preterm infants after birth to prevent or treat severe infections. However, interactions between gastrointestinal health and systemic immune development following neonatal antibiotics are unclear. Methods: Using a preterm pig model, we investigated the systemic immune effects of four days of antibiotics (AB) treatment just after birth. Preterm pigs received enteral AB for 4 days and were compared with controls (water) until 9 days after birth (n = 28–32). Blood samples were collected at birth and on days 5, 7, and 9. Gut samples were collected on day 9. Results: Expression of TLR2, TLR3, S100A9, and IL10 differed by day 5, 7 and 9 in blood for controls, while AB-treated showed delay of these temporal developments. On day 9, blood transcriptomics revealed 1765 DEGs (1090 downregulated) in AB-treated pigs compared with controls, with suppression of inflammatory and energy metabolism pathways. The suppression was associated with lower intestinal permeability, bacterial adhesion and gut inflammation. The findings suggest that enteral AB exposure after preterm birth, reduces not only gut inflammation, but also delay systemic immune cell development. Conclusion: Neonatal AB treatment might reduce gut inflammation; however, it may cause subsequent reduced capacity to combat systemic infections. Impact statement: Neonatal antibiotics attenuate gut inflammation and systemic immune development. Effects persist after cessation of antibiotic treatment. Inflammatory pathways in blood are associated with gut health parameters. This study underscores the complex interplay between gastrointestinal health and systemic immune function. Neonatal antibiotics may influence risk of infectious complications even after treatment.