Effect of Maternal Administration with All-Trans Retinoic Acid on Lungs of Neonatal Pigs

(1) Background: How to reduce respiratory diseases in animals is a matter of great concern, and this study aimed to investigate the effect of maternal administration with all-trans retinoic acid (ATRA) on the lung health of neonatal pigs. (2) Methods: Fifteen sows were randomly allotted to one of five ATRA groups (0, 4, 8, 16, and 32 mg/kg diet), respectively; on average, from days 12 to 95 after insemination, lung samples of neonatal pigs were harvested for HE staining, 16S DNA sequencing, and transcriptomic analysis. (3) Results: Compared to neonatal pigs from the ATRA0 group, neonatal pigs from the ATRA4 group had an increased (<i>p</i> > 0.05) alveolar number and the thinner (<i>p</i> < 0.05) alveolar septum, higher (<i>p</i> < 0.05) abundance of <i>Akkermansia</i> and <i>unidentified_Mitochondria</i>, and a lower (<i>p</i> < 0.05) abundance of <i>Acinetobacter</i>, <i>Cutibacterium</i>, <i>Stenotrophomonas</i>, <i>Enterobacter</i>, <i>Saccharomonospora</i>, and <i>Alistipes</i> in the lungs. Maternal supplementation of ATRA at 4 mg/kg diet had the benefits of reducing pathogen virulence and drug resistance, but it poses the risk of increasing the resistance to β-lactam antibiotics. In addition, it reduced (<i>p</i> < 0.05) the virulence, drug resistance, and stress tolerant capacity of potential pathogens (Proteobacteria, <i>Acinetobacter</i>, <i>Cupriavidus</i>, and <i>Pseudomonas</i>), enriched the highest number of genes in neuroactive ligand-receptor interaction pathway, and decreased gene expression of CCL11 and IL9 in the asthma pathway. (4) Conclusions: Maternal supplementation of ATRA at 4 mg/kg diet can strengthen the lung health of neonatal pigs by improving alveolar development, decreasing the number and virulence of pathogens, and down-regulating the expression of asthma-related genes.