Abstract

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.

Highlights

  • Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in pregnancy

  • Our research indicated that there was no significant clustering by Principal coordinate analysis (PCoA) analysis, patients with ICP have increased rare bacteria at different phylogenetic levels

  • Our results illustrated that all 638 KEGG Orthologs and 136 in 138 KEGG pathways were less abundant in ICP patients compared to the controls

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Summary

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that 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. Intrahepatic cholestasis of pregnancy (ICP) is a common liver disease that occurs during pregnancy. Typical symptoms of ICP include itching without a rash that is typically localized to the soles of the feet and palms of the hands. Symptoms include elevated levels of both liver enzymes and serum bilirubin. In a large prospective national cohort study in the United Kingdom in 2014, women with severe ICP had significantly elevated risks of preterm delivery, stillbirth, and admissions for treatment into neonatal units as compared to control pregnant subjects [2]. Other symptoms that can affect the fetus include meconiumstained amniotic fluids, neonatal depression, and respiratory distress syndrome [3,4,5]

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