Vitamin A and Retinoic Acid Exhibit Protective Effects on Necrotizing Enterocolitis by Regulating Intestinal Flora and Enhancing the Intestinal?Epithelial Barrier

摘要

BackgroundExaggerated inflammation that characterizes necrotizing enterocolitis (NEC) is caused by the invasion of pathogens through an immature intestinal barrier. Vitamin A (VA) and retinoic acid (RA) play important roles in the growth of epithelial tissue and in modulating immune function. ObjectiveTo investigate the roles of VA and RA in the development of NEC. MethodsLevels of serum retinol in patients and in a NEC mouse model were detected with high-performance liquid chromatography. Bacterial communities of NEC mice treated with VA or PBS were detected by high-throughput sequencing.In?vitroandin?vivo, levels of inflammatory factors were measured by ELISA and RT-PCR, and expression levels of claudin-1, occludin, and ZO-1 were detected by Western blotting. Transepithelial electrical resistance (TEER) was measured in Caco-2?cell monolayers. ResultsThe level of VA in the NEC patients was lower than in the control patients. In the NEC mice that were treated with VA versus PBS, the proportion ofEscherichia-Shigellawas lower, while the abundance ofBacteroideswas markedly higher. Bothin?vivoandin?vitro, the levels of inflammatory factors were significantly reduced, while the expression levels of claudin-1, occludin, and ZO-1 were increased, after the VA and RA treatments. Meanwhile, TEER was increased and lipopolysaccharide-induced damage was reduced in Caco-2?cell monolayers after RA treatment. ConclusionsThese results suggest that VA may regulate intestinal flora, alleviate inflammatory reactions, and enhance the intestinal epithelial barrier in NEC. Thus, VA may be an effective drug for providing protection against NEC in newborns.