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
Research background

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

Research motivation

Women with ICP have a significantly increased risk of preterm birth, stillbirth and admission to the neonatal unit for treatment. At present, there is no specific drug for the treatment of ICP in clinical practice.

Research objectives

We speculate that changes in serum metabolism caused by ICP may influence the intestinal tract circumstance and thus the intestinal microbiome. The gut microbiota may represent a mechanism by which ICP affects the health of pregnant women and fetuses. Our goal is to find the novel therapeutic strategies of ICP in the field of the gut microbiota.

Research methods

The serum nontarget metabolomes from each group 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.

Research results

ICP patients have critical differences in the intestinal microflora composition (beta diversity) from that in healthy controls. 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.

Research conclusions

The serum metabolome was significantly correlated with the gut microbiota, indicating that the gut microbiota plays an important role in the occurrence and development of ICP. Our findings suggest that the intestinal microbiome can be used as a therapeutic target to provide new strategies for the diagnosis and treatment of ICP.

Research perspectives

Our group will study gut microbiota and metabolome changes before and after drug treatment to provide a new regimen for ICP treatment. In the future we will also conduct intervention studies using prebiotics, probiotics and synbiotics to promote the establishment of beneficial microbiota and investigate whether it can have a positive impact on the health of ICP patients.