Acute necrotizing enterocolitis of preterm piglets is characterized by dysbiosis of ileal mucosa-associated bacteria
Acute necrotizing enterocolitis of preterm piglets is characterized by dysbiosis of ileal mucosa-associated bacteria
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DOI：
10.4161/gmic.2.4.16332
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发表时间：
2011-01-01
期刊：
影响因子：
12.2
通讯作者：
Gookin, Jody L.
中科院分区：
文献类型：
--
作者：
Azcarate-Peril, M. Andrea;Foster, Derek M.;Gookin, Jody L.
对坏死性小肠结肠炎 (NEC) 发病机制中涉及的细菌的研究受到婴儿脆弱性、仅限于粪便的分析、使用基于培养的方法以及缺乏临床相关动物模型的限制。本研究使用独特的早产仔猪模型来表征 NEC 易感肠道区域微生物组组成的自发差异。早产仔猪 (n = 23) 经剖腹产并饲养 30 小时，在此期间，52% 的仔猪出现 NEC。对回肠内容物、回肠粘膜和结肠粘膜的细菌 DNA 进行 PCR 扩增，进行末端限制性片段长度多态性 (TRFLP) 分析和靶向 16S rDNAq PCR。与回肠内容物和结肠粘膜相比，早产回肠粘膜的细菌多样性明显缺失。早产回肠仅限于变形菌门、厚壁菌门、蓝藻门和绿弯菌门。在患有 NEC 的仔猪中，回肠粘膜的独特特征是厚壁菌门数量增加和门的多样性（包括放线菌和未培养的细菌）。五个特定的 TRFLP 图谱，与丁酸梭菌、新生儿梭菌、解蛋白梭菌、链霉菌属最接近。和 Leptolyngbya spp.，明显更普遍或仅在患有 NEC 的仔猪样本中观察到。梭菌总数。 NEC 回肠粘膜样本中的 C. 和 C. butyricum 显着较高，但回肠内容物或结肠粘膜样本中则没有。这些结果为回肠粘膜作为与 NEC 相关的特定生态失调研究的焦点提供了强有力的支持，并表明梭状芽胞杆菌属、放线菌门和蓝藻门的成员在早产仔猪 NEC 的发病机制中发挥着重要作用。
Investigation of bacteria involved in pathogenesis of necrotizing enterocolitis (NEC) is limited by infant fragility, analysis restricted to feces, use of culture-based methods and lack of clinically-relevant animal models. This study used a unique preterm piglet model to characterize spontaneous differences in microbiome composition of NEC-predisposed regions of gut. Preterm piglets (n = 23) were cesarean-delivered and nurtured for 30 hours over which time 52% developed NEC. Bacterial DNA from ileal content, ileal mucosa and colonic mucosa were PCR amplified, subjected to terminal restriction fragment length polymorphism (TRFLP) analysis and targeted 16S rDNAq PCR. Preterm ileal mucosa was specifically bereft in diversity of bacteria compared to ileal content and colonic mucosa. Preterm ileum was restricted to representation by only Proteobacteria, Firmicutes, Cyanobacteria and Chloroflexi. In piglets with NEC, ileal mucosa was uniquely characterized by increases in number of Firmicutes and diversity of phyla to include Actinobacteria and uncultured bacteria. Five specific TRFLP profiles, corresponding in closest identity to Clostridium butyricum, C. neonatale, C. proteolyticum, Streptomyces spp. and Leptolyngbya spp., were significantly more prevalent or observed only among samples from piglets with NEC. Total numbers of Clostridium spp. and C. butyricum were significantly greater in samples of NEC ileal mucosa but not ileal content or colonic mucosa. These results provide strong support for ileal mucosa as a focus for investigation of specific dysbiosis associated with NEC and suggest a significant role for Clostridium spp., and members of the Actinobacteria and Cyanobacteria in the pathogenesis of NEC in preterm piglets.