Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia
Copyright © 2020 the American Physiological Society. During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.
Publication Source (Journal or Book title)
American Journal of Physiology - Lung Cellular and Molecular Physiology
Willis, K., Siefker, D., Aziz, M., White, C., Mussarat, N., Gomes, C., Bajwa, A., Pierre, J., Cormier, S., & Talati, A. (2020). Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia. American Journal of Physiology - Lung Cellular and Molecular Physiology, 318 (2), L407-L418. https://doi.org/10.1152/AJPLUNG.00561.2018