Grishin Anatoly, Bowling Jordan, Bell Brandon, Wang Jin, Ford Henri R
Division of Pediatric Surgery, Children's Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027; Department of Surgery, Keck School of Medicine of the University of Southern California, 4650 Sunset Boulevard, Los Angeles, CA 90027.
Department of Surgery, Keck School of Medicine of the University of Southern California, 4650 Sunset Boulevard, Los Angeles, CA 90027.
J Pediatr Surg. 2016 Jan;51(1):13-7. doi: 10.1016/j.jpedsurg.2015.10.006. Epub 2015 Oct 22.
Necrotizing enterocolitis remains one of the most vexing problems in the neonatal intensive care unit. Risk factors for NEC include prematurity, formula feeding, and inappropriate microbial colonization of the GI tract. The pathogenesis of NEC is believed to involve weakening of the intestinal barrier by perinatal insults, translocation of luminal bacteria across the weakened barrier, an exuberant inflammatory response, and exacerbation of the barrier damage by inflammatory factors, leading to a vicious cycle of inflammation-inflicted epithelial damage. Nitric oxide (NO), produced by inducible NO synthase (iNOS) and reactive NO oxidation intermediates play a prominent role in the intestinal barrier damage by inducing enterocyte apoptosis and inhibiting the epithelial restitution processes, namely enterocyte proliferation and migration. The factors that govern iNOS upregulation in the intestine are not well understood, which hampers efforts in developing NO/iNOS-targeted therapies. Similarly, efforts to identify bacteria or bacterial colonization patterns associated with NEC have met with limited success, because the same bacterial species can be found in NEC and in non-NEC subjects. However, microbiome studies have identified the three important characteristics of early bacterial populations of the GI tract: high diversity, low complexity, and fluidity. Whether NEC is caused by specific bacteria remains a matter of debate, but data from hospital outbreaks of NEC strongly argue in favor of the infectious nature of this disease. Studies in Cronobacter muytjensii have established that the ability to induce NEC is the property of specific strains rather than the species as a whole. Progress in our understanding of the roles of bacteria in NEC will require microbiological experiments and genome-wide analysis of virulence factors.
坏死性小肠结肠炎仍然是新生儿重症监护病房中最棘手的问题之一。坏死性小肠结肠炎的危险因素包括早产、配方奶喂养以及胃肠道微生物定植不当。坏死性小肠结肠炎的发病机制被认为涉及围产期损伤导致肠道屏障减弱、腔内细菌穿过薄弱屏障的易位、过度的炎症反应以及炎症因子加剧屏障损伤，从而导致炎症所致上皮损伤的恶性循环。由诱导型一氧化氮合酶（iNOS）产生的一氧化氮（NO）和活性NO氧化中间体通过诱导肠上皮细胞凋亡和抑制上皮修复过程，即肠上皮细胞增殖和迁移，在肠道屏障损伤中起重要作用。肠道中调控iNOS上调的因素尚不清楚，这阻碍了开发针对NO/iNOS的治疗方法的努力。同样，识别与坏死性小肠结肠炎相关的细菌或细菌定植模式的努力也取得了有限的成功，因为在坏死性小肠结肠炎患者和非坏死性小肠结肠炎患者中都能发现相同的细菌种类。然而，微生物组研究已经确定了胃肠道早期细菌群体的三个重要特征：高度多样性、低复杂性和流动性。坏死性小肠结肠炎是否由特定细菌引起仍存在争议，但医院坏死性小肠结肠炎暴发的数据有力地支持了这种疾病的感染性本质。对穆氏阪崎肠杆菌的研究表明，诱导坏死性小肠结肠炎的能力是特定菌株的特性，而不是整个物种的特性。我们对细菌在坏死性小肠结肠炎中作用的理解取得进展将需要微生物学实验和毒力因子的全基因组分析。
