Bacterial Microbiome Dynamics in Post Pull-Through Hirschsprung-Associated Enterocolitis (HAEC): An Experimental Study Employing the Endothelin Receptor B-Null Mouse Model.
Bacterial Microbiome Dynamics in Post Pull-Through Hirschsprung-Associated Enterocolitis (HAEC): An Experimental Study Employing the Endothelin Receptor B-Null Mouse Model.
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DOI：
10.3389/fsurg.2018.00030
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发表时间：
2018
影响因子：
1.8
通讯作者：
Frykman PK
中科院分区：
文献类型：
--
作者：
Cheng Z;Zhao L;Dhall D;Ruegger PM;Borneman J;Frykman PK
先天性巨结肠相关性小肠结肠炎(HAEC)是先天性巨结肠(HSCR)患儿中最常见的潜在威胁生命的并发症，即使在进行了明确的矫正手术后也是如此。越来越多的证据表明，肠道微生物区系可能与小肠结肠炎的病因有关，因此本研究的目的是使用HAEC后的小鼠模型来比较发生HAEC的动物和未患HAEC的动物的粪便细菌群落。10只EDNRB−/−小鼠和80只野生型小鼠接受显微外科手术，分别在手术时、术后2周、4周或发生小肠结肠炎时收集粪便。所有动物的中段结肠都被收集、准备和组织学分级，以确定是否患有小肠结肠炎。提取粪便DNA，用Illumina测序分析细菌16S rRNA基因。6只EDNRB−/−小鼠发生了HAEC，平均小肠结肠炎评分为5.7，而其余4只突变小鼠和8只WT小鼠在4周后仍未患上小肠结肠炎。CHO1分析显示，HAEC组的α多样性低于WT组，而EDNRB−/−小鼠在β多样性分析中显示出与WT组明显不同的细菌群落。与无HAEC组和WT组相比，最显著的发现是Akkermansia的比例增加，类杆菌的比例减少，提示Akkermansia可能有助于小肠结肠炎的发展，而类杆菌可能具有保护作用。在HAEC中减少的种类较少的属是Dysgonomas和Clostridium XIVa，它们可能起到保护作用。这是首次发现Akkermansia可能在HAEC中发挥作用，或者是作为一种有助于小肠结肠炎发病的致病分类群，或者可能是一种为应对炎症而扩大的保护性共生分类群。这些发现表征了HAEC发生后肠道微生物群落的动态变化，提示HSCR患者可能存在可识别的细菌群落差异，这些差异是发生HAEC的高风险因素。
Hirschsprung-associated enterocolitis (HAEC) is the most frequent potentially life-threatening complication in children with Hirschsprung disease (HSCR) even after definitive corrective surgery. Mounting evidence suggests that intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to use a mouse model of post pull-through HAEC to compare the fecal bacterial communities of animals which developed HAEC to those free of enterocolitis. Ten Ednrb−/− and 8wild type mice underwent the microsurgical pull-through surgery, and stool was collected at the time of surgery, and then either at 2 and 4 weeks after the operation, or when the mice developed enterocolitis. The mid-colon of all animals was collected, prepared and histologically graded for enterocolitis. Fecal DNA was isolated and bacterial 16S rRNA genes analyzed using Illumina sequencing. Six Ednrb−/− mice developed HAEC with a mean enterocolitis score of 5.7, while the remaining 4 mutant and 8 WT mice remained free of enterocolitis by 4 weeks. The HAEC group had lower alpha diversity by Chao1 analysis compared with WT group, while the Ednrb−/− mice demonstrated distinct bacterial communities from WT mice on beta diversity analysis. The most striking finding was increased proportion of Akkermansia and reduced Bacteroidetes compared with the NO HAEC and WT groups, suggesting Akkermansia may contribute to development of enterocolitis while Bacteroidetes may be protective. Less abundant genera that were reduced in HAEC were Dysgonomas and Clostridium XIVa which may play a protective role. This is the first study to identify Akkermansia as potentially playing a role in HAEC, either as a pathobiont taxa contributing to pathogenesis of enterocolitis, or possibly a protective commensal taxa expanded in response to inflammation. These findings characterized the dynamic shifts in the gut microbial communities through the onset of post pull-through HAEC, and suggests that there may be identifiable bacterial community differences in HSCR patients that are high risk for developing HAEC.
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影响因子：
3.7
作者：
Frykman PK;Nordenskjöld A;Kawaguchi A;Hui TT;Granström AL;Cheng Z;Tang J;Underhill DM;Iliev I;Funari VA;Wester T;HAEC Collaborative Research Group (HCRG)
通讯作者：
HAEC Collaborative Research Group (HCRG)
影响因子：
1.7
作者：
Frykman PK;Short SS
通讯作者：
Short SS
影响因子：
11
作者：
Berry, David;Schwab, Clarissa;Loy, Alexander
通讯作者：
Loy, Alexander
影响因子：
2.4
作者：
Cheng, Zhi;Dhall, Deepti;Frykman, Philip K.
通讯作者：
Frykman, Philip K.
DOI：
10.1073/pnas.1000080107
发表时间：
2011-03-15
影响因子：
11.1
作者：
Caporaso, J. Gregory;Lauber, Christian L.;Knight, Rob
通讯作者：
Knight, Rob