Hegde Shalini G, Devi Sarita, Pasanna Roshni M, Padashetty Chetan, Shubha Attibele Mahadevaiah, Mukhopadhyay Arpita, Kurpad Anura V
Department of Paediatric Surgery, Bengaluru, Karnataka, India.
Department of Division of Nutrition, St. John's Research Institute, Bengaluru, Karnataka, India.
J Indian Assoc Pediatr Surg. 2024 Jan-Feb;29(1):6-12. doi: 10.4103/jiaps.jiaps_134_23. Epub 2024 Jan 12.
Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early gestational development of the ENS is dependent on the prenatal maternal metabolic environment, the objective of this pilot study was to explore the role of specific maternal plasma metabolites in the etiology of HSCR.
In this cross-sectional study, postnatal (as a surrogate for prenatal) plasma samples were obtained from mothers of children diagnosed with HSCR ( = 7) and age-matched mothers of normal children ( = 6). The plasma metabolome was analyzed by ultra-high-pressure liquid chromatography and mass spectrometry. Metabolites were identified by mzCloud using Compound Discoverer software. Using an untargeted metabolomics workflow, metabolites with case versus control group differences were identified.
A total of 268 unique plasma metabolites were identified and annotated in maternal plasma. Of these, 57 were significantly different between case and control groups ( < 0.05, -test). Using a false discovery rate corrected cutoff of 10% to adjust for multiple comparisons, 19 metabolites were significantly different in HSCR cases, including carnitines, medium-chain fatty acids, and glutamic acid. Pathways affected were for amino acid and lipid metabolism.
Disordered prenatal metabolic pathways may be involved in the etiopathogenesis of HSCR in the developing fetus. This is the first study to assess maternal plasma metabolomics in HSCR.
先天性巨结肠症（HSCR）是一种病因不明的先天性疾病，会影响肠神经系统（ENS）。由于肠神经系统的早期妊娠发育依赖于产前母体代谢环境，本初步研究的目的是探讨特定母体血浆代谢物在先天性巨结肠症病因中的作用。
在这项横断面研究中，从诊断为先天性巨结肠症的儿童的母亲（n = 7）和年龄匹配的正常儿童的母亲（n = 6）中获取产后（作为产前的替代）血浆样本。通过超高压液相色谱和质谱分析血浆代谢组。使用Compound Discoverer软件通过mzCloud鉴定代谢物。采用非靶向代谢组学工作流程，鉴定病例组与对照组之间存在差异的代谢物。
在母体血浆中总共鉴定并注释了268种独特的血浆代谢物。其中，病例组和对照组之间有57种存在显著差异（P < 0.05，t检验）。使用10%的错误发现率校正临界值来调整多重比较，19种代谢物在先天性巨结肠症病例中存在显著差异，包括肉碱、中链脂肪酸和谷氨酸。受影响的途径涉及氨基酸和脂质代谢。
产前代谢途径紊乱可能参与发育中胎儿先天性巨结肠症的发病机制。这是第一项评估先天性巨结肠症母体血浆代谢组学的研究。
