Department of Pediatric Surgery, Children's Hospital, Helsinki University Central Hospital.
Immunobiology Research Program, Faculty of Medicine.
J Pediatr Gastroenterol Nutr. 2018 Nov;67(5):594-600. doi: 10.1097/MPG.0000000000001999.
The aim of the study was to characterize the microbiota profiles of patients with Hirschsprung disease (HD) and to evaluate this in relation to postoperative bowel function and the incidence of Hirschsprung-associated enterocolitis (HAEC).
All patients operated on for HD at our center between 1987 and 2011 were invited to answer questionnaires on bowel function and to participate in a clinical follow-up for laboratory investigations, including fecal DNA extraction, fecal calprotectin (FC), and brush border lactase (LCT) genotyping. The microbiota compositions of patients with HD were compared with those of healthy controls aged between 2 and 7 years.
The microbiota composition of eligible patients with HD (n = 34; median age 12 [range, 3-25] years) differed from the healthy controls (n = 141), showing decreased overall microbial richness (P < 0.005). Seventy-seven percent had experienced HAEC. Normal maturation of the intestinal flora was not observed, but patients had a significantly increased abundance of Proteobacteria among other taxa (P < 0.005) resulting in a reduced carbohydrate degradation potential, as predicted by the taxonomic composition. Genetic lactase deficiency was present in 17% and did not correlate with bowel symptoms. No patients reported active HAEC at the time of sampling and FC was within the normal range in all samples.
Patients with HD and HAEC had a significantly altered intestinal microbiome compared to healthy individuals, characterized by a lack of richness and pathologic expansions of taxa, particularly Enterobacteria and Bacilli. Further evaluation is needed to identify whether these observations are intrinsic to HD or secondary to the recurrent use of antibiotics during early childhood.
本研究旨在分析先天性巨结肠（HD）患者的肠道微生物群特征，并评估其与术后肠道功能和先天性巨结肠相关性肠炎（HAEC）的发生率的关系。
我们邀请了 1987 年至 2011 年间在本中心接受 HD 手术的所有患者回答有关肠道功能的问卷，并参与临床随访以进行实验室检查，包括粪便 DNA 提取、粪便钙卫蛋白（FC）和刷状缘乳糖酶（LCT）基因分型。将 HD 患者的微生物群落组成与 2 至 7 岁的健康对照组进行比较。
符合条件的 HD 患者（n=34；中位年龄 12 岁[范围 3-25 岁]）的微生物群落组成与健康对照组（n=141）不同，表现为整体微生物丰富度降低（P<0.005）。77%的患者经历过 HAEC。未观察到肠道菌群的正常成熟，但患者的变形菌门等其他分类群的丰度显著增加（P<0.005），导致碳水化合物降解潜力降低，这与分类组成预测的结果一致。乳糖酶基因缺陷在 17%的患者中存在，但与肠道症状无关。在采样时没有患者报告有活动性 HAEC，并且所有样本的 FC 均在正常范围内。
与健康个体相比，患有 HAEC 的 HD 患者的肠道微生物组存在明显改变，其特征为丰富度降低和分类群的病理性扩张，尤其是肠杆菌科和芽孢杆菌科。需要进一步评估这些观察结果是 HD 固有特征还是由于儿童早期反复使用抗生素所致。
