EA 4065, Faculty of Pharmacy, Paris Descartes University, Paris, France.
Department of Neonatal Medicine, Nantes University Hospital, Nantes, France.
Appl Environ Microbiol. 2018 Mar 19;84(7). doi: 10.1128/AEM.02428-17. Print 2018 Apr 1.
We aimed at identifying potential bacterial factors linking clostridia with necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress responses, cellular cytotoxicity, and inflammatory capabilities of the largest collection of and strains isolated from fecal samples of NEC preterm neonates (PN) and control PNs. When strain characteristics were used as explanatory variables, a statistical discriminant analysis allowed the separation of NEC and control strains into separate groups. Strains isolated from NEC PN were characterized by a higher viability at 30°C ( = 0.03) and higher aerotolerance ( = 0.01), suggesting that NEC strains may have a competitive and/or survival advantage in the environmental gastrointestinal tract conditions of NEC PN. Heat-treated NEC bacteria induced higher production of interleukin-8 in Caco-2 cells ( = 0.03), suggesting proinflammatory activity. , bacteria, bacterial components, and fecal filtrates showed variable cytotoxic effects affecting the cellular network and/or cell viability, without specific association with NEC or control samples. Altogether, our data support the existence of a specific clostridial strain signature associated with NEC. Clostridia are part of the commensal microbiota in preterm neonates (PN). However, microbiota analyses by culture and metagenomics have linked necrotizing enterocolitis (NEC) and intestinal colonization with clostridial species. Nevertheless, little is known about the specific characteristics that may be shared by clostridia associated with NEC compared to commensal clostridia. Therefore, our goal was to identify specific bacterial factors linking clostridial strains with NEC. We report the existence of a specific bacterial signature associated with NEC and propose that activation of the innate immune response may be a unifying causative mechanism for the development of NEC independent of a specific pathogenic organism. The present study provides new insights into NEC pathophysiology that are needed for better diagnostics and strategies for implementing prevention of the disease.
我们旨在确定与坏死性小肠结肠炎（NEC）相关的梭状芽胞杆菌的潜在细菌因素。我们比较了从 NEC 早产儿（PN）和对照 PN 的粪便样本中分离的最大 和 菌株的表型特征、应激反应、细胞毒性和炎症能力。当将菌株特征用作解释变量时，统计判别分析允许将 NEC 和对照菌株分为不同的组。从 NEC PN 分离的菌株在 30°C 时具有更高的存活率（=0.03）和更高的耐氧性（=0.01），这表明 NEC 菌株可能在 NEC PN 的环境胃肠道条件下具有竞争和/或生存优势。热处理的 NEC 细菌诱导 Caco-2 细胞中白细胞介素-8 的产生更高（=0.03），表明具有促炎活性。 ，细菌，细菌成分和粪便滤液显示出可变的细胞毒性作用，影响细胞网络和/或细胞活力，与 NEC 或对照样品没有特定关联。总的来说，我们的数据支持与 NEC 相关的特定梭状芽胞杆菌菌株特征的存在。梭状芽胞杆菌是早产儿（PN）共生微生物群的一部分。然而，通过培养和宏基因组学进行的微生物组分析将坏死性小肠结肠炎（NEC）和肠道定植与梭状芽胞杆菌物种联系起来。然而，与共生梭状芽胞杆菌相比，与 NEC 相关的梭状芽胞杆菌可能具有的特定特征知之甚少。因此，我们的目标是确定与 NEC 相关的特定细菌因素。我们报告了与 NEC 相关的特定细菌特征的存在，并提出激活先天免疫反应可能是独立于特定病原体的 NEC 发展的统一致病机制。本研究为 NEC 病理生理学提供了新的见解，这对于更好的诊断和实施疾病预防策略是必要的。
