Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.

Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.
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DOI:
10.1371/journal.pone.0124172
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
HAEC Collaborative Research Group (HCRG)
HAEC Collaborative Research Group (HCRG)
中科院分区:
综合性期刊3区
文献类型:
--
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)

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发展为可能危及生命的小肠结肠炎是先天性巨结肠症(HSCR)患儿最常见的并发症,即使在明确的矫正手术后也是如此。肠道微生物群可能导致小肠结肠炎的病因,因此本研究的目的是比较患有Hirschsprung相关小肠结肠炎(HAEC)的儿童与从未患有小肠结肠炎的HSCR患者的粪便细菌和真菌群落。18例已完成确定性手术的先天性巨结肠患者入组:9例有HAEC病史,9例无HAEC病史。分离粪便DNA,并使用下一代测序和数据分析对16 S和ITS-1区域进行测序,用于物种鉴定。与HSCR组相比,HAEC组细菌组成显示厚壁菌门和疣微菌门适度减少,拟杆菌门和变形菌门增加。相比之下,HAEC组的粪便真菌组成显示出显著的多样性减少,与HSCR组相比,马拉色菌和酵母菌减少。HAEC组中最引人注目的发现是念珠菌属分离为“高负荷”患者,其中97.8%为C。白色念珠菌和2.2%念珠菌。热带型与“低负荷”型相比,C.白色念珠菌占73%。热带植物有趣的是,即使是低负荷HAEC组也改变了念珠菌群落结构,与HSCR患者中更多样化的念珠菌种群相比,只有两个物种。这是第一项确定念珠菌属在HAEC中可能发挥作用的研究,无论是作为小肠结肠炎(或治疗)的结果而扩大的肠道菌群,还是可能作为导致HAEC发病机制的致病菌。这些发现表明HAEC患者的肠道微生物生态系统中的生态失调,使得可能存在使患者易患HAEC的真菌和细菌的优势。
Development of potentially life-threatening enterocolitis is the most frequent complication in children with Hirschsprung disease (HSCR), even after definitive corrective surgery. Intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to compare the fecal bacterial and fungal communities of children who developed Hirschsprung-associated enterocolitis (HAEC) with HSCR patients who had never had enterocolitis. Eighteen Hirschsprung patients who had completed definitive surgery were enrolled: 9 had a history of HAEC and 9 did not. Fecal DNA was isolated and 16S and ITS-1 regions sequenced using Next Generation Sequencing and data analysis for species identification. The HAEC group bacterial composition showed a modest reduction in Firmicutes and Verrucomicrobia with increased Bacteroidetes and Proteobacteria compared with the HSCR group. In contrast, the fecal fungi composition of the HAEC group showed marked reduction in diversity with increased Candida sp., and reduced Malassezia and Saccharomyces sp. compared with the HSCR group. The most striking finding within the HAEC group is that the Candida genus segregated into “high burden” patients with 97.8% C. albicans and 2.2% C. tropicalis compared with “low burden” patients 26.8% C. albicans and 73% C. tropicalis. Interestingly even the low burden HAEC group had altered Candida community structure with just two species compared to more diverse Candida populations in the HSCR patients. This is the first study to identify Candida sp. as potentially playing a role in HAEC either as expanded commensal species as a consequence of enterocolitis (or treatment), or possibly as pathobioants contributing to the pathogenesis of HAEC. These findings suggest a dysbiosis in the gut microbial ecosystem of HAEC patients, such that there may be dominance of fungi and bacteria predisposing patients to development of HAEC.
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