Qihong Zheng1, Liming Shen2,3, Danqing Zhao4, Huajie Zhang1, Yi Liang5, Yuhua Zhu4, Naseer Ullah Khan1, Xukun Liu1, Jun Zhang1, Jing Lin1,6, Xiaoxiao Tang1,7. 1. College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, People's Republic of China. 2. College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, People's Republic of China. slm@szu.edu.cn. 3. Brain Disease and Big Data Research Institute, Shenzhen University, Shenzhen, 518071, People's Republic of China. slm@szu.edu.cn. 4. Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, People's Republic of China. 5. Department of Clinical Nutrition, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, People's Republic of China. 6. Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, People's Republic of China. 7. Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen, 518071, People's Republic of China.
Abstract
INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is one of the more common complications in the middle and late stages of pregnancy, which requires early detection and intervention. OBJECTIVE: The aim of the study is to investigate the changes in the metabolic profile of bile acids (BAs) in plasma of pregnant women with ICP and to look biomarkers for the diagnosis and grading of ICP, and to explore the disease mechanism. METHODS: The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze plasma BAs. RESULTS: Twenty-seven BAs can be quantified in all participants. Among them, 22 BAs were identified as differential BAs between ICP and control groups. Five BAs include 3β-CA, 3β-DCA, CDCA-3Gln, NCA, and Tβ-MCA, were found to be associated with ICP for the first time. Nine BAs include NCA, GCA, GCDCA, GHCA, GUDCA, HCA, TCA, TCDCA and THCA, can be used as possible ICP diagnostic biomarkers. Four BAs, i.e., GLCA, THCA, GHCA and TLCA-3S may be used as potential biomarkers for ICP grading. CONCLUSION: There were significant differences in plasma BA profiles between ICP patients and the control. The BA profiles of mild ICP group and severe ICP group partially overlapped. Potential diagnostic and grading BA markers were identified. A significant characteristic of ICP group was the increase of conjugated BAs. A mechanism to sustain the equilibrium of BA metabolism and adaptive response has been developed in ICP patients to accelerate excretion and detoxification.
INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is one of the more common complications in the middle and late stages of pregnancy, which requires early detection and intervention. OBJECTIVE: The aim of the study is to investigate the changes in the metabolic profile of bile acids (BAs) in plasma of pregnant women with ICP and to look biomarkers for the diagnosis and grading of ICP, and to explore the disease mechanism. METHODS: The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze plasma BAs. RESULTS: Twenty-seven BAs can be quantified in all participants. Among them, 22 BAs were identified as differential BAs between ICP and control groups. Five BAs include 3β-CA, 3β-DCA, CDCA-3Gln, NCA, and Tβ-MCA, were found to be associated with ICP for the first time. Nine BAs include NCA, GCA, GCDCA, GHCA, GUDCA, HCA, TCA, TCDCA and THCA, can be used as possible ICP diagnostic biomarkers. Four BAs, i.e., GLCA, THCA, GHCA and TLCA-3S may be used as potential biomarkers for ICP grading. CONCLUSION: There were significant differences in plasma BA profiles between ICP patients and the control. The BA profiles of mild ICP group and severe ICP group partially overlapped. Potential diagnostic and grading BA markers were identified. A significant characteristic of ICP group was the increase of conjugated BAs. A mechanism to sustain the equilibrium of BA metabolism and adaptive response has been developed in ICP patients to accelerate excretion and detoxification.