Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Department of Pediatric Surgery, Ghent University Hospital, Ghent University, Ghent, Belgium.
Sci Rep. 2021 Aug 9;11(1):16167. doi: 10.1038/s41598-021-95589-0.
Hirschsprung's disease (HD) is a congenital structural abnormality of the colon seen in approximately 1 to 5000 live births. Despite surgical correction shortly after presentation, up to 60% of patients will express long-term gastrointestinal complaints, including potentially life-threatening Hirschsprung-associated enterocolitis (HAEC). In this study fecal samples from postoperative HD patients (n = 38) and their healthy siblings (n = 21) were analysed using high-resolution liquid chromatography-mass spectrometry aiming to further unravel the nature of the chronic gastrointestinal disturbances. Furthermore, within the patient group, we compared the faecal metabolome between patients with and without a history of HAEC as well as those diagnosed with short or long aganglionic segment. Targeted analysis identified several individual metabolites characteristic for all HD patients as well as those with a history of HAEC and long segment HD. Moreover, multivariate models based on untargeted data established statistically significant (p < 0.05) differences in comprehensive faecal metabolome in the patients' cohort as a whole and in patients with a history of HAEC. Pathway analysis revealed the most impact on amino sugar, lysine, sialic acid, hyaluronan and heparan sulphate metabolism in HD, as well as impaired tyrosine metabolism in HAEC group. Those changes imply disruption of intestinal mucosal barrier due to glycosaminoglycan breakdown and dysbiosis as major metabolic changes in patients' group and should be further explored for potential diagnostic or treatment targets.
先天性巨结肠症（HD）是一种结肠先天性结构异常，在大约 1 至 5000 例活产儿中可见。尽管在出现后不久进行了手术矫正，但多达 60%的患者会长期出现胃肠道不适，包括潜在危及生命的先天性巨结肠相关性结肠炎（HAEC）。在这项研究中，我们使用高分辨率液相色谱-质谱法分析了术后 HD 患者（n=38）和他们健康兄弟姐妹（n=21）的粪便样本，旨在进一步揭示慢性胃肠道紊乱的性质。此外，在患者组中，我们比较了有和无 HAEC 病史以及短段和长段无神经节细胞巨结肠患者的粪便代谢组。靶向分析确定了几种个体代谢物，这些代谢物是所有 HD 患者以及有 HAEC 病史和长段 HD 患者的特征。此外，基于非靶向数据的多元模型在整个患者队列以及有 HAEC 病史的患者中建立了统计学上显著（p<0.05）的综合粪便代谢组差异。途径分析显示，HD 中对氨基糖、赖氨酸、唾液酸、透明质酸和硫酸乙酰肝素代谢的影响最大，以及 HAEC 组中酪氨酸代谢受损。这些变化意味着由于糖胺聚糖分解和微生物失调导致肠道黏膜屏障破坏，是患者组中的主要代谢变化，应进一步探索其作为潜在的诊断或治疗靶点的可能性。
