Dataset Information

Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy.

ABSTRACT:

Background and aims

Women with severe intrahepatic cholestasis of pregnancy (ICP) are at higher risks of fetal complications and without effective treatments. Changes in gut microbiota in pregnancy were found to be related to the altered intestinal bile acid composition, so we aimed to explore the alterations of microbiota in the gut of ICP patients.

Methods

A total of 90 women were recruited, including 45 ICP patients and 45 healthy controls. The gut microbiota communities of ICP group were compared to control group through 16S ribosomal RNA gene sequencing. The results were then confirmed by real-time polymerase chain reaction (PCR) and generalized linear model (GLM). Furthermore, we analyzed the relationships between microbiota and the severity of ICP.

Results

A total of seven genera and nine taxa with differential abundances between the ICP patients and the controls were identified. All of the seven genera were verified through real-time PCR, and three key genera Parabacteroides, Flavonifractor, and Megamonas were confirmed by using the GLM model. Further analysis found that the genera Escherichia_Shigella, Olsenella, and Turicibacter were enriched in the severe ICP group, the microbial gene function related to biosynthesis of unsaturated fatty acids and propanoate metabolism were also increased in them.

Conclusions

Overall, our study was the first in Asia to demonstrate an association between gut microbiota and ICP. Our findings would contribute to a better understanding of the occurrence of ICP.

SUBMITTER: Zhan Q

PROVIDER: S-EPMC8120235 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder that specifically occurs in pregnancy. Elevated levels of liver transaminases aspartate aminotransferase, alanine aminotransferase and serum bilirubin levels are common biochemical characteristics in ICP. The disorder is associated with an increased risk of premature delivery and stillbirth. The characterization of the potential microbiota in ICP could go a long way in the prevention and treatment of this pregnancy disease.MethodsA total of 58 patients were recruited for our study: 27 ICP patients and 31 healthy pregnant subjects with no ICP. The V3 and V4 regions of the 16S rDNA collected from fecal samples of both diseased and control groups were amplified. 16S rRNA gene amplicon sequencing was then performed on gut microbiota. Sequencing data were analyzed and the correlation between components of microbiota and patient ICP status was found. Related metabolic pathways, relative abundance and significantly different operational taxonomic units (OTUs) between ICP and controls were also identified.ResultsElevated levels of total bile acid, ALT, AST, Dbil and Tbil were recorded or observed in ICP subjects as compared to the control. Gut microbiota in pregnant women was dominated by four major phyla and 27 core genera. PCoA analysis results indicated that there was no significant clustering in Bray-Curtis distance matrices. Our results showed that there was a correlation between specific OTUs and measured clinical parameters of pregnant women. Comparison at the different taxonomy levels revealed high levels of abundance of Blautia and Citrobacter in ICP patients. At the family level, Enterobacteriaceae and Leuconostocaceae were higher in ICP patients. 638 KEGG Orthologs and 138 pathways significantly differed in the two groups. PLS-DA model with VIP plots indicated a total of eight genera and seven species were key taxa in ICP and control groups.ConclusionsOur research indicated that although there was no significant clustering by PCoA analysis, patients with ICP have increased rare bacteria at different phylogenetic levels. Our results also illustrated that all 638 KEGG Orthologs and 136 in 138 KEGG pathways were less abundant in ICP patients compared to the controls.

Project description:BackgroundIntrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood.AimTo investigate the link between the gut microbiota and serum metabolome in ICP patients.MethodsIn 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.ResultsThe 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.ConclusionOur 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.