The complete change in bile acids and steroids in systematic metabolomics applied to the intrahepatic cholestasis of pregnancy†

IF 3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular omics Pub Date : 2023-03-31 DOI:10.1039/D2MO00305H

Hualin Xu, Yupin Xu, Guoqiang Zhao, Xukun Fu, Jian Zhao, Huaqian Wang, Yuliang Cai and Hongmei Lin

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Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific hepatobiliary disease, leading to an abnormal increase in total bile acid in the blood of pregnant women. To systematically explore the similarities and differences in metabolites and metabolic pathways among three types of biological samples from ICP women, a study of 18 ICP and 6 healthy (as a normal control) pregnant women was performed to investigate their clinical information and biochemical features. Based on validated LC–MS/MS methods 1–5 for hydrophilic and hydrophobic metabolites (molecular weight <2000 Dalton), an untargeted-metabolomic strategy was applied to 24 pregnant women to determine the metabolites from 22 serum, 15 placental and 22 urine samples. Then 1137 metabolites from serum, 876 metabolites from placental tissue and 311 metabolites from urine with a coefficient of variation <30% in the pooled quality control samples were found. Furthermore, orthogonal partial least squares–discriminate analysis (OPLS–DA), correlation analysis, chemical enrichment analysis and metabolic pathway analysis were carried out by a bioinformatics process. On the OPLS–DA model analysis, the metabolites in urine were better than those in serum or placental tissue to reflect the metabolic changes of ICP disease. Some metabolites were significantly changed in serum (n = 71), placental tissue (n = 46) and urine (n = 36), such as bile acids, triacylglycerols, lysoPCs, and steroids. Primary bile acid biosynthesis was the main metabolic pathway in ICP disease, and taurine and hypotaurine metabolism and sphingolipid metabolism were also found. More specifically, bile acids increased and steroids decreased in the serum, placental and urine samples. For complex metabolic diseases such as ICP disease, untargeted-metabolomic analysis of multiple biological samples could provide a systematic understanding of the changes in metabolic types and pathways.

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胆汁酸和类固醇在系统代谢组学中的完全变化适用于妊娠肝内胆汁淤积症†

妊娠期肝内胆汁淤积症(ICP)是一种妊娠期特有的肝胆疾病，可导致孕妇血液中总胆汁酸异常升高。为系统探讨ICP妇女三种生物样本代谢物及代谢途径的异同，对18例ICP妇女和6例健康孕妇(作为正常对照)进行了临床资料和生化特征的研究。基于经过验证的亲水和疏水代谢物(分子量为2000道尔顿)的LC-MS /MS方法1-5，采用非靶向代谢组学策略对24名孕妇进行了22份血清、15份胎盘和22份尿液样本的代谢物测定。血清代谢物1137个，胎盘组织代谢物876个，尿液代谢物311个，变异系数为30%。利用生物信息学方法进行正交偏最小二乘判别分析(OPLS-DA)、相关分析、化学富集分析和代谢途径分析。在OPLS-DA模型分析中，尿液中的代谢物比血清或胎盘组织中的代谢物更能反映ICP疾病的代谢变化。血清(n = 71)、胎盘组织(n = 46)和尿液(n = 36)中的一些代谢物发生了显著变化，如胆汁酸、甘油三酯、溶血opcs和类固醇。原发性胆汁酸的生物合成是ICP的主要代谢途径，同时还存在牛磺酸、次牛磺酸代谢和鞘脂代谢。更具体地说，血清、胎盘和尿液样本中的胆汁酸增加，类固醇减少。对于复杂的代谢性疾病，如ICP病，对多种生物样品进行非靶向代谢组学分析可以系统地了解代谢类型和途径的变化。

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来源期刊

Molecular omics Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

5.40

自引率

3.40%

发文量

期刊介绍： Molecular Omics publishes high-quality research from across the -omics sciences. Topics include, but are not limited to: -omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance -omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets -omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques -studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field. Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits. Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.