The Role of Bacteria in Necrotizing Enterocolitis: Understanding the Forest for the Trees.
The Role of Bacteria in Necrotizing Enterocolitis: Understanding the Forest for the Trees.
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细菌在坏死性小肠结肠炎中的作用：只见树木，见森林。
DOI：
10.1159/000437205
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发表时间：
2015
期刊：
影响因子：
2.5
通讯作者：
McElroy,StevenJ
中科院分区：
文献类型：
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作者：
McElroy,StevenJ
新生儿坏死性小肠结肠炎（NEC）继续困扰着早产儿，他们的父母和照顾这些患者的卫生保健从业人员。尽管在50多年前首次发现[1，2]，但发病率保持不变，一般人群中每1，000例活产中有1.1例受影响，出生体重低于1，500 g的早产儿中高达7%[3，4]。尽管进行了大量的研究，但对NEC病理生理学的理解仍然不完整。自最初的描述以来，临床医生一直认为细菌在疾病过程中发挥着作用。1975年，Santulli et al. [5]他说：“疾病的发展似乎有三个基本组成部分：肠粘膜损伤，细菌的存在和代谢底物的可用性，即喂养。“关于NEC爆发的广泛数据和相关菌血症的共同发现进一步加强了这一信念。甚至NEC的分类也在很大程度上取决于是否存在肠积气，这是当粘膜破裂后细菌侵入并发酵肠壁中存在的底物时发生的。在该疾病的动物模型中，无菌小鼠不能发展NEC [6]，而暴露于梭菌属诱导无菌鹌鹑盲肠中的NEC样病变[7]，并且TLR4（Toll样受体4）信号级联的激活导致啮齿动物中NEC样病变的发展[8，9，10]。然而，尽管有这些压倒性的证据，没有统一的致病机制或病原体已被确定为NEC的发展。有趣的是，该疾病通常在没有菌血症或特定病原体的情况下发生[11，12]。最近的研究人员提出了一种假设，即NEC的结果部分是由于正常肠道植物群的扰动，而不是特定病原体的生长[13，14]。在过去的十年中，研究人员使用下一代序列技术来检查患有和没有NEC的婴儿的肠道微生物群的组成。然而，即使这种方法也导致了相互矛盾的报告[15，16]，阐明了肠道系统中宿主-微生物相互作用的复杂性。
Neonatal necrotizing enterocolitis (NEC) continues to vex premature infants, their parents and the health-care practitioners who care for these patients. Despite first being recognized over 50 years ago [1, 2], the incidence remains unchanged, affecting 1.1 per 1,000 live births in the general population and up to 7% of premature infants born with birth weights less than 1,500 g [3, 4]. Despite vigorous study, the understanding behind the pathophysiology of NEC remains incomplete. Since its initial descriptions, clinicians have believed that bacteria play a role in the disease process. In 1975, Santulli et al.[5] stated:‘There would appear to be three essential components to the development of the disease: injury to the intestinal mucosa, the presence of bacteria, and the availability of a metabolic substrate, ie feedings.'This belief has been further strengthened by extensive data on outbreaks of NEC and the common finding of associated bacteremia. Even the classification of NEC is in large part determined by the presence of pneumatosis intestinalis, which is felt to occur when bacteria invade and ferment the substrate present in the intestinal wall following mucosal disruption. In animal models of the disease, germ-free mice fail to develop NEC [6], while exposure to Clostridium sp. induces NEC-like lesions in the ceca of gnotobiotic quails [7] and the activation of the TLR4 (Toll-like receptor 4) signal cascade leads to the development of NEC-like lesions in rodents [8, 9, 10]. However, despite this overwhelming evidence, no unifying causative mechanism or pathogenic organism has been identified for the development of NEC. Intriguingly, the disease often occurs in the absence of bacteremia or specific pathogens [11, 12].More recent investigators have put forth the hypothesis that NEC results in part due to a perturbation of the normal intestinal flora instead of the growth of a specific pathogen [13, 14]. Over the past decade, researchers have used next-generation sequence technologies to examine the composition of the intestinal microbiota in infants with and without NEC. However, even this approach has led to conflicting reports [15, 16], illuminating the complexity that exists in the host-microbe interaction in the intestinal system.