Parker Kristopher D, Mueller Jessica L, Westfal Maggie, Goldstein Allan M, Ward Naomi L
Department of Botany, University of Wyoming, Laramie, WY, USA.
Department of Natural Sciences, Middle Georgia State University, Cochran, GA, USA.
Pediatr Surg Int. 2022 Nov;38(11):1541-1553. doi: 10.1007/s00383-022-05191-2. Epub 2022 Aug 11.
Hirschsprung disease is a neurointestinal disease that occurs due to failure of enteric neural crest-derived cells to complete their rostrocaudal migration along the gut mesenchyme, resulting in aganglionosis along variable lengths of the distal bowel. Despite the effective surgery that removes the aganglionic segment, children with Hirschsprung disease remain at high risk for developing a potentially life-threatening enterocolitis (Hirschsprung-associated enterocolitis). Although the etiology of this enterocolitis remains poorly understood, several recent studies in both mouse models and in human subjects suggest potential involvement of gastrointestinal microbiota in the underlying pathogenesis of Hirschsprung-associated enterocolitis.
We present the first study to exploit the Illumina MiSeq next-generation sequencing platform within a longitudinal framework focused on microbiomes of Hirschsprung-associated enterocolitis in five patients. We analyzed bacterial communities from fecal samples collected at different timepoints starting from active enterocolitis and progressing into remission.
We observed compositional differences between patients largely attributable to variability in age at the time of sample collection. Remission samples across patients exhibited compositional similarity, including enrichment of Blautia, while active enterocolitis samples showed substantial variability in composition.
Overall, our findings provide continued support for the role of GI microbiota in the pathogenesis of Hirschsprung-associated enterocolitis.
先天性巨结肠症是一种神经肠道疾病，由肠神经嵴衍生细胞未能沿肠道间充质完成其头尾向迁移所致，导致远端肠管不同长度出现神经节缺失。尽管手术切除无神经节段有效，但先天性巨结肠症患儿仍面临发生潜在危及生命的小肠结肠炎（先天性巨结肠相关小肠结肠炎）的高风险。尽管这种小肠结肠炎的病因仍知之甚少，但最近在小鼠模型和人类受试者中的几项研究表明，胃肠道微生物群可能参与先天性巨结肠相关小肠结肠炎的潜在发病机制。
我们开展了第一项研究，在纵向框架内利用Illumina MiSeq下一代测序平台，聚焦于5例先天性巨结肠相关小肠结肠炎患者的微生物群。我们分析了从活动性小肠结肠炎开始并进入缓解期的不同时间点采集的粪便样本中的细菌群落。
我们观察到患者之间的组成差异很大程度上归因于样本采集时年龄的变异性。各患者的缓解期样本表现出组成相似性，包括布劳特氏菌属的富集，而活动性小肠结肠炎样本的组成则表现出很大的变异性。
总体而言，我们的研究结果继续支持胃肠道微生物群在先天性巨结肠相关小肠结肠炎发病机制中的作用。
