Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2020; 26(46): 7338-7351
Published online Dec 14, 2020. doi: 10.3748/wjg.v26.i46.7338
Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients
Guo-Hua Li, Shi-Jia Huang, Xiang Li, Xiao-Song Liu, Qiao-Ling Du
Guo-Hua Li, Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
Shi-Jia Huang, Xiang Li, Xiao-Song Liu, Qiao-Ling Du, Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
Author contributions: Du QL and Li GH proposed and designed the study; Li X, Liu XS and Huang SJ collected data; Li GH and Huang SJ analyzed and interpreted data; Li GH drafted the manuscript; Du QL and Huang SJ reviewed and edited the manuscript; Du QL provided administrative support and funding acquisition; All authors read, revised and approved the final draft.
Supported by the Technology Project of Shanghai Pudong New District Health and Family Planning Commission, No. PW2019D-9.
Institutional review board statement: This study was approved by the Ethics Committee of Shanghai First Maternity and Infant Health Hospital (KS2035).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The raw sequencing data have been submitted to the NCBI Sequence Read Archive under accession number PRJNA657645.
STROBE statement: The manuscript has been prepared and revised according to the STROBE statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Qiao-Ling Du, PhD, Doctor, Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699 West Gaoke Road, Shanghai 200040, China.
Received: September 9, 2020
Peer-review started: September 9, 2020
First decision: September 29, 2020
Revised: October 9, 2020
Accepted: November 4, 2020
Article in press: November 4, 2020
Published online: December 14, 2020

Intrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood.


To investigate the link between the gut microbiota and serum metabolome in ICP patients.


In this study, a total of 30 patients were recruited, including 15 patients with ICP (disease group) and 15 healthy pregnant patients (healthy group). The serum nontarget metabolomes from both groups were determined. Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups. By comparing the differences in the microbiota and metabolite compositions between the two groups, the relationship between the gut microbiota and serum metabolites was also investigated.


The Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis, bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls. In addition, some pathways related to protein metabolism were also enriched in the ICP patients. The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition (beta diversity) between the ICP patients and healthy controls. At the phylum level, we observed that the relative abundance of Firmicutes was higher in the healthy group, while Bacteroidetes were enriched in the disease group. At the genus level, most of the bacteria depleted in ICP are able to produce short-chain fatty acids (e.g., Faecalibacterium, Blautia and Eubacterium hallii), while the bacteria enriched in ICP are associated with bile acid metabolism (e.g., Parabacteroides and Bilophila). Our results also showed that specific genera were associated with the serum metabolome.


Our study showed that the serum metabolome was altered in ICP patients compared to healthy controls, with significant differences in the bile, taurine and hypotaurine metabolite pathways. Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota, which may further affect the course of progression of ICP.

Keywords: Intrahepatic cholestasis in pregnancy, Metabolome, Gut microbiota, Bile acids

Core Tip: This study is the first to investigate the consequences of intrahepatic cholestasis in pregnancy (ICP) with respect to the serum metabolome and gut microbiota. Our data suggest that ICP can cause significant changes in the serum metabolome. Changes in the relative abundance of bile acid-related compounds in serum due to ICP may have an impact on gut microbiota, which in turn may threaten the safety of pregnant women and fetuses. Our findings also suggest a mechanism of ICP that is associated with the microbiota via changes in serum metabolites.