肠道菌群失调在新生儿坏死性小肠结肠炎中的研究进展  

Research advances in gut bacteria dysbiosis and neonatal necrotizing enterocolitis

作　　者：葛贵杰 吕志宝[1] Ge Guijie;Lyu Zhibao(Department of General Surgery,Shanghai Children’s Hospital,Shanghai Jiaotong University,Shanghai 200062,China)

机构地区：[1]上海市儿童医院上海交通大学附属儿童医院普外科,200062

出　　处：《中华小儿外科杂志》2020年第3期285-288,F0003,共5页Chinese Journal of Pediatric Surgery

基　　金：上海市自然科学基金(18ZR1431300)。

摘　　要：新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)是好发于新生儿尤其早产、低出生体重儿的胃肠道急症,主要表现为肠壁局部或全层的炎性损伤甚至坏死,与早产、配方奶喂养和肠道细菌异常定植和增殖等多种因素综合作用相关。在极低出生体重儿中,NEC的发病率在5%~10%,死亡率在20%~30%,是导致早产儿尤其低出生体重儿死亡的重要病因之一。近期的研究表明,肠道菌群失调可以激活不受控的促炎反应从而导致NEC的发生发展。在早产儿的肠道菌群组成中,潜在致病菌较多,如肠杆菌科、葡萄球菌属、肠球菌属和梭菌属等;有益共生菌缺乏,如专性厌氧菌Negativicutes、双歧杆菌属和丙酸杆菌属等;且细菌多样性降低。迄今为止,对于哪种细菌与NEC发病是因果关系尚无共识,但几项前瞻性研究表明出现在NEC之前的变形菌门失调颇具代表性。来源于革兰氏阴性变形菌的脂多糖(LPS)激活TLR4信号通路,介导强烈的炎症反应,加之肠道菌群失调与未成熟肠的相互作用,有学者提出将早产儿肠道细菌异常定植作为NEC主要诱发因素的假设。双歧杆菌、丙酸杆菌等益生菌的施用可能通过激活NOD2信号通路或调节淋巴细胞平衡的方式来干预肠道菌群失调所致危害,为NEC的早期防护提供一种新策略。As a severe gastrointestinal disease with multiple causative factors,necrotizing enterocolitis(NEC)is one of the most common devastating necro-inflammatory intestinal injuries in neonates,particularly among preterm or very-low-birth-weight infants.Prematurity,formula feeding,bacterial colonization and proliferation are the major risk factors.The incidence of NEC is 5-10%among very-low-birth-weight neonates and the mortality 20-30%.Recent studies suggest that NEC results from gut bacteria dysbiosis activating an uncontrolled proinflammatory response.In gut microbiota composition of preterm infants,there are more potential pathogens of Enterobacteriaceae,Staphylococcus,Enterococcus and Clostridium.And there is a paucity of beneficial commensal organisms such as strict anaerobic bacteria(esp.Negativicutes),Bifidobacterium and Propionibacterium.Also the diversity of microbiota declines.To date,there is no consensus on which specific bacterial strains are causally correlated with NEC development.Several prospective studies have shown a marked dysbiosis with phylum Proteobacteria before NEC onset.Lipopolysaccharide(LPS),a product of Gram-negative Proteobacteria,activates TLR4 signaling pathway of mediating an exaggerated inflammatory response.In addition,an interaction between gut bacteria dysbiosis and an immature intestine has also been implicated in the pathogenesis of NEC.Thus some researchers hypothesized that inappropriate colonization of premature intestine may be a major predisposing factor for NEC.The administration of probiotics such as Bifidobacterium and Propionibacterium may mitigate the damage caused by gut bacteria dysbiosis through activating NOD2 signaling pathway or regulating lymphocyte balance.Thus it may help devise a new strategy for early protection of NEC.

关 键 词：新生儿 坏死性小肠结肠炎 肠道菌群失调 

分 类 号：R722.1[医药卫生—儿科]