Influence of nutrition and maternal bonding on postnatal lung development

In infancy, microbial colonization and maturation of immune cells coincide at mucosal sites and are decisive for postnatal lung development. External factors favor and interfere with neonatal lung development, thereby affecting the long-term respiratory health of the individual. Nutrition and environment are critical external factors that profoundly influence neonatal lung development during the "neonatal window of opportunity." To obtain human-relevant data, a large animal model with lung maturity at birth comparable to that of humans is highly relevant.Objective: The aim of this study was to investigate the influence of nutrition and maternal bonding on early postnatal lung maturation, respiratory immunity, and microbial colonization of the lung in a human-relevant large animal model, the pig. Furthermore, measures to compensate for impaired neonatal lung maturation, such as breast milk feeding, maternal material transfer, and maternal bonding, were investigated. The postnatal lung development in conventionally reared piglets was characterized immunologically and histomorphologically from the neonatal to the weaning phase of the piglets. In parallel, newborn piglets were separated from their mothers, kept isolated and fed with infant formula based on bovine milk or received milked sow's milk. In addition, maternal material was used to enrich the isolated environment of formula-fed piglets. Lung growth, respiratory immune responses, morphology and lung microbiota composition of the aforementioned reared newborn piglets were compared with suckling piglets reared with the mother sow. Postnatal lung development in conventionally reared piglets was highly dynamic, associated with pronounced tissue remodeling, cellular proliferation, marked activation of myeloid lung parenchymal cells, and accumulation of activated T cells of the type 1 phenotype. During the neonatal period, alveoli formation was associated with the infiltration of 'ILC2-like' cells into the porcine lung. Formula feeding of newborn piglets separated from the mother sow after birth resulted in delayed postnatal lung maturation and reduced pulmonary Th1 differentiation, which was alleviated by feeding sow milk. The developing lung microbiota was lower in richness and diversity in newborn piglets isolated from the sow and significantly correlated with delayed lung maturation. Bacterial species from feces and environment contributed substantially to the composition of the lung microbiota, and the transfer of maternal material promoted the maturation of the pulmonary immune system, reflected in increased Th1 differentiation. In piglets returned to their mothers within the first 3 days after birth, the adverse effects of formula feeding on postnatal lung maturation were reversible. Maternal bonding and breast milk promote postnatal lung growth, respiratory immunity and microbial colonization of newborn piglets. Postnatal lung maturation and immunity are influenced by the developing local microbiota, which are modulated by the neonatal environment, nutritional factors, and duration of altered early life conditions.