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首页> 外文期刊>EBioMedicine >Inflammation associated ethanolamine facilitates infection by Crohn's disease-linked adherent-invasive Escherichia coli
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Inflammation associated ethanolamine facilitates infection by Crohn's disease-linked adherent-invasive Escherichia coli

机译：炎症相关的乙醇胺促进克罗恩病相关的粘附侵袭性大肠杆菌的感染

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Background The predominance of specific bacteria such as adherent-invasive Escherichia coli (AIEC) within the Crohn's disease (CD) intestine remains poorly understood with little evidence uncovered to support a selective pressure underlying their presence. Intestinal ethanolamine is however readily accessible during periods of intestinal inflammation, and enables pathogens to outcompete the host microbiota under such circumstances. Methods Quantitative RT-PCR (qRT-PCR) to determine expression of genes central to ethanolamine metabolism; transmission electron microscopy to detect presence of bacterial microcompartments (MCPs); in vitro infections of both murine and human macrophage cell lines examining intracellular replication of the AIEC-type strain LF82 and clinical E. coli isolates in the presence of ethanolamine; determination of E. coli ethanolamine utilization ( eut ) operon transcription in faecal samples from healthy patients, patients with active CD and the same patients in remission following treatment. Results Growth on the intestinal short chain fatty acid propionic acid (PA) stimulates significantly increased transcription of the eut operon (fold change relative to glucose: 16.9; p -value .01). Additionally ethanolamine was accessible to intra-macrophage AIEC and stimulated significant increases in growth intracellularly when it was added extracellularly at concentrations comparable to those in the human intestine. Finally, qRT-PCR indicated that expression of the E. coli eut operon was increased in children with active CD compared to healthy controls (fold change increase: 4.72; P ??.02). After clinical remission post-exclusive enteral nutrition treatment, the same CD patients exhibited significantly reduced eut expression (Pre vs Post fold change decrease: 15.64; P ??.01). Interpretation Our data indicates a role for ethanolamine metabolism in selecting for AIEC that are consistently overrepresented in the CD intestine. The increased E. coli metabolism of ethanolamine seen in the intestine during active CD, and its decrease during remission, indicates ethanolamine use may be a key factor in shaping the intestinal microbiome in CD patients, particularly during times of inflammation. Fund This work was funded by Biotechnology and Biological Sciences Research Council (BBSRC) grants BB/K008005/1 & BB/P003281/1 to DMW; by a Tenovus Scotland grant to MJO; by Glasgow Children's Hospital Charity, Nestle Health Sciences, Engineering and Physical Sciences Research Council (EPSRC) and Catherine McEwan Foundation grants awarded to KG; and by a Natural Environment Research Council (NERC) fellowship (NE/L011956/1) to UZI. The IBD team at the Royal Hospital for Children, Glasgow are supported by the Catherine McEwan Foundation and Yorkhill IBD fund. RKR and RH are supported by NHS Research Scotland Senior fellowship awards.
机译：背景技术克罗恩病（CD）肠内特定细菌（例如黏附性大肠杆菌（AIEC））的优势仍然知之甚少，几乎没有发现证据支持它们存在的选择性压力。然而，肠内乙醇胺很容易在肠内炎症期间进入，并在这种情况下使病原体能够胜过宿主菌群。方法采用定量RT-PCR（qRT-PCR）确定乙醇胺代谢关键基因的表达;透射电子显微镜检测细菌微区室（MCP）的存在;在乙醇胺存在下，检查鼠和人巨噬细胞系的体外感染，以检查AIEC型菌株LF82和临床大肠杆菌分离株的细胞内复制;测定健康患者，活动性CD患者和治疗后缓解的同一患者粪便样本中大肠杆菌乙醇胺利用率（ut）操纵子的转录。结果肠道短链脂肪酸丙酸（PA）上的生长刺激了出口操纵子的转录显着增加（相对于葡萄糖的倍数变化：> 16.9; p值<.01）。另外，乙醇胺可被巨噬细胞内的AIEC所利用，并且当其以与人肠中的浓度相当的浓度在细胞外添加时，可刺激细胞内生长的显着增加。最后，qRT-PCR表明，与健康对照组相比，患有活动性CD的儿童大肠杆菌大肠操纵子的表达增加了（倍数变化增加：＞ 4.72;P≤＜.02）。排他性肠内营养治疗后临床缓解后，相同的CD患者表现出明显的EUT表达下降（Pre与Post倍数变化降低：> 15.64; P 0.01）。解释我们的数据表明乙醇胺代谢在选择CD肠中始终过量表达的AIEC中的作用。在活动性CD期间，肠道中乙醇胺的大肠杆菌代谢增加，而在缓解期则减少，这表明乙醇胺的使用可能是影响CD患者肠道微生物组的关键因素，尤其是在炎症时期。资金这项工作由生物技术和生物科学研究委员会（BBSRC）资助，DMW获得BB / K008005 / 1和BB / P003281 / 1。由苏格兰Tenovus授予MJO;由格拉斯哥儿童医院慈善机构，雀巢健康科学，工程与物理科学研究委员会（EPSRC）和凯瑟琳·麦克尤恩基金会授予KG;由自然环境研究委员会（NERC）授予UZI的研究金（NE / L011956 / 1）。格拉斯哥皇家儿童医院的IBD团队得到了凯瑟琳·麦克尤恩基金会和Yorkhill IBD基金的支持。 RKR和RH得到了NHS Research苏格兰高级研究金的支持。

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