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Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy.

ABSTRACT: BACKGROUND:Intrahepatic 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. METHODS:A 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. RESULTS:Elevated 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. CONCLUSIONS:Our 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.

SUBMITTER: Li R

PROVIDER: S-EPMC7682054 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy.

Li Rong R Chen Xuehai X Liu Zhongzhen Z Chen Yan Y Liu Chuan C Ye Lingfei L Xiao Liang L Yang Zhenjun Z He Jian J Wang Wen-Jing WJ Qi Hongbo H

BMC gastroenterology 20201123 1

<h4>Background</h4>Intrahepatic 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 pregnanc ...[more]

PMID: 33225888

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Project description:BackgroundPrevious observational cohort studies have shown that the composition of the gut microbiota is related to the risk of intrahepatic cholestasis of pregnancy (ICP), although it is unclear if the association is causative. This study used Mendelian randomization (MR) to systematically examine whether the gut microbiota was causally linked to ICP.MethodsWe obtained the genome-wide association study (GWAS) summary statistics of gut microbiota and ICP from published GWASs. Maximum likelihood (ML), MR-Egger regression, weighted median, inverse variance weighted (IVW), and weighted model were used to investigate the causal association between gut microbiota and ICP. We further conducted a series of sensitivity analyses to confirm the robustness of the primary results of the MR analyses. Reverse MR analysis was performed on the bacterial taxa that were reported to be causally linked to ICP risk in forwarding MR analysis to evaluate the possibility of reverse causation.ResultsMR analysis revealed that phylum Tenericutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), class Bacteroidia (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), class Mollicutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), and order Bacteroidales (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), and were positively associated with the risk of ICP. And we identified that the relative abundance of genus Dialister (OR: 0.562, 95%CI: 0.323-0.977, P = 0.041), genus Erysipelatoclostridium (OR: 0.695, 95%CI: 0.490-0.987, P = 0.042), genus Eubacterium (brachy group) (OR: 0.661, 95%CI: 0.497-0.880, P = 0.005), genus Eubacterium (hallii group) (OR: 0.664, 95%CI: 0.451-0.977, P = 0.037), genus Holdemania (OR: 0.590, 95%CI: 0.414-0.840, P = 0.003), genus Ruminococcus (torques group) (OR: 0.448, 95%CI: 0.235-0.854, P = 0.015), and genus Veillonella (OR: 0.513, 95%CI: 0.294-0.893, P = 0.018) were related to a lower risk of ICP. Additional sensitivity analyses confirmed the robustness of the association between specific gut microbiota composition and ICP. No evidence of reverse causality from ICP to identified bacterial taxa was found in the findings of the reverse MR analyses.ConclusionsUnder MR assumptions, our findings propose new evidence of the relationship between gut microbiota and ICP risk. Our results show that the gut microbiota may be useful target of intervention for ICP.

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.

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Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy.

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Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy.

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