Maternal antibiotic exposure disrupts microbiota and exacerbates hyperoxia-induced lung injury in neonatal mice

Background: Perinatal antibiotic treatment alters intestinal microbiota and augments hyperoxia-induced lung injury in mice offspring. The effect of maternal antibiotic treatment (MAT) during pregnancy on the lung microbiota and its relationship with lung injury remains unknown. Methods: We fed timed-pregnant C57BL/6N mice sterile drinking water containing antibiotics from gestational day 15 to delivery. Neonatal mice were reared in either room air (RA) or hyperoxia (85% O₂) from postnatal days 1 to 7. Four study groups were obtained: control + RA, control + O₂, MAT + RA, and MAT + O₂. On postnatal day 7, lung and intestinal microbiota were sampled from the left lung and lower gastrointestinal tract. The right lung was harvested for histology and cytokine analysis. Results: MAT during pregnancy significantly reduced the total number of commensal bacteria in the intestine and birth body weight of newborn mice compared with control newborn mice. Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT. Neonatal hyperoxia altered the composition and diversity of intestinal and lung microbiota and MAT further exacerbated neonatal hyperoxia-induced intestinal and lung dysbiosis. Conclusions: MAT during pregnancy exacerbates hyperoxia-induced lung injury probably through the modulation of intestinal and lung microbiota in neonatal mice. Impact: MAT during pregnancy reduced the total number of commensal bacteria in the intestine.Neonatal hyperoxia altered the composition and diversity of intestinal and lung microbiota.MAT exacerbated neonatal hyperoxia-induced intestinal and lung dysbiosis.Neonatal hyperoxia exposure impaired alveolarization and angiogenesis, which was exacerbated by MAT.Avoiding and carefully using antibiotics during pregnancy is a potential therapeutic target for preventing lung injury in hyperoxia-exposed infants.