Liu Wenhu, Wang Qiang, Chang Jinxia, Bhetuwal Anup, Bhattarai Nisha, Ni Xin
Department of Gynecology and Obstetrics, International Collaborative Research Center for Medical Metabolomics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, China.
School of Pharmacy, School of Basic Medical Sciences and Forensic Medical, North Sichuan Medical College, Nanchong, China.
Front Physiol. 2022 Jul 11;13:848508. doi: 10.3389/fphys.2022.848508. eCollection 2022.
Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse pregnancy to the mother and fetus. As yet, the metabolic profiles and the association of the clinical features remain obscure. Fifty-seven healthy pregnant women and 52 patients with ICP were recruited in this study. Plasma samples were collected from pregnancies who received prenatal care between 30 and 36 weeks. Untargeted metabolomics to portray the metabolic profiles were performed by LC/MS. Multivariate combined with the univariate analysis was performed to screen out differential metabolites between the ICP and control groups. A de-biased sparse partial correlation (DSPC) network analysis of differential metabolites was conducted to explore the potential mutual regulation among metabolites on the basis of de-sparsified graphical lasso modeling. The pathway analysis was carried out using MetaboAnalyst. Linear regression and Pearson correlation analysis was applied to analyze correlations of bile acid levels, metabolites, newborn weights, and pregnancy outcomes in ICP patients. Conspicuous metabolic changes and choreographed metabolic profiles were disclosed: 125 annotated metabolites and 18 metabolic pathways were disturbed in ICP patients. DSPC networks indicated dense interactions among amino acids and their derivatives, bile acids, carbohydrates, and organic acids. The levels of total bile acid (TBA) were increased in ICP patients with meconium-stained amniotic fluid (MSAF) compared with those without MSAF. An abnormal tryptophan metabolism, elevated long chain saturated fatty acids and estrone sulfate levels, and a low-antioxidant capacity were relevant to increased bile acid levels. Newborn weights were significantly associated with the levels of bile acids and some metabolites of amino acids. Our study revealed the metabolomic profiles in circulation and the correlation of the metabolites with clinical features in ICP patients. Our data suggest that disturbances in metabolic pathways might be associated with adverse pregnancy outcomes.
妊娠期肝内胆汁淤积症（ICP）与母婴不良妊娠结局风险增加相关。迄今为止，其代谢谱以及临床特征之间的关联仍不清楚。本研究招募了57名健康孕妇和52例ICP患者。收集了在孕30至36周接受产前检查的孕妇的血浆样本。通过液相色谱/质谱联用技术进行非靶向代谢组学分析以描绘代谢谱。采用多变量结合单变量分析筛选出ICP组与对照组之间的差异代谢物。基于去稀疏化图式套索模型，对差异代谢物进行去偏稀疏偏相关（DSPC）网络分析，以探索代谢物之间潜在的相互调控关系。使用MetaboAnalyst进行通路分析。应用线性回归和Pearson相关分析来分析ICP患者胆汁酸水平、代谢物、新生儿体重和妊娠结局之间的相关性。结果揭示了明显的代谢变化和精心编排的代谢谱：ICP患者中有125种注释代谢物和18条代谢通路受到干扰。DSPC网络表明氨基酸及其衍生物、胆汁酸、碳水化合物和有机酸之间存在密集的相互作用。与无胎粪污染羊水（MSAF）的ICP患者相比，有MSAF的患者总胆汁酸（TBA）水平升高。异常的色氨酸代谢、长链饱和脂肪酸和硫酸雌酮水平升高以及抗氧化能力低下与胆汁酸水平升高有关。新生儿体重与胆汁酸水平和一些氨基酸代谢物显著相关。我们的研究揭示了ICP患者循环中的代谢组学谱以及代谢物与临床特征之间的相关性。我们的数据表明代谢途径的紊乱可能与不良妊娠结局有关。
