母乳寡糖对坏死性小肠结肠炎的防治作用研究进展

Research advances of preventing and treating necrotizing enterocolitis with human milk oligosaccharides

坏死性小肠结肠炎(necrotizing enterocolitis, NEC)是一种主要影响新生儿尤其早产儿的急性肠道炎症疾病, 死亡率高达20%~30%, 其发病机制尚不明确, 并且尚无安全有效的治疗方式。母乳喂养是目前已知的极少数NEC防治手段之一, 而母乳中蕴含的保护性功能组分是其发挥肠道保护作用的物质基础。人乳寡糖(human milk oligosaccharides, HMOs)是一组在人类母乳中含量高达5~15 g/L的游离复杂低聚糖, 其多向性的肠道保护活性被逐步揭示。HMOs极少在胃肠道消化并能完整地到达结直肠, 并在此参与微生物群落的构建;与上皮细胞和免疫系统细胞上表达的表面凝集素受体结合, 调节新生儿肠道屏障和免疫稳态等。本综述聚焦HMOs的肠道保护作用和机制的最新研究进展, 阐述HMOs结构及其分泌规律、HMOs靶向NEC致病靶点的保护作用机制, 以期为HMOs及相关结构作为抗NEC的天然产物进行研发提供理论依据和研究思路。

As one specific type of acute intestinal inflammation primarily affecting neonates,especially premature infants,necrotizing enterocolitis(NEC)carries a fatality rate of 20%-30%.Its pathogenesis has remained elusive.There is currently no safe and effective treatment.Breast-feeding is one of the few known ways of preventing and curing NEC.The protective functional components in breast milk act as a material basis for its intestinal protection.Human milk oligosaccharides(HMOs)are a diverse group of structurally complex unconjugated glycans.With a high concentration of(5-15)g/L in human breast milk,polymorphic intestinal protection has been gradually revealed.Rarely digested in gastrointestinal tract,HMOs could reach colorectal intact where they are involved in constructing microbial communities.HMOs bind to surface lectin receptors expressed on epithelial cells and immune system cells for regulating neonatal intestinal barrier and immune homeostasis.Focusing upon the latest researches of intestinal protection and mechanisms of HMOs,this review discussed the structural and secretory regularity of HMOs and protective mechanism of HMOs against pathogenic target of NEC to provide theoretical and research rationales for researches and developments of HMOs and related structures as natural products against NEC.