Published online Dec 14, 2020. doi: 10.3748/wjg.v26.i46.7338
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
Processing time: 95 Days and 23.6 Hours
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.
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.