Characterization of Gut Microbiota Associated with Clinical Parameters in Intrahepatic Cholestasis of Pregnant Patients

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Abstract Background: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that specifically occurs in pregnancy. Elevated levels of liver transaminases aspartate aminotransferase (AST), alanine aminotransferase (ALT) and serum bilirubin levels are common biochemical characteristics in ICP. The disorder is associated with an increased risk of premature delivery and stillbirth. We hypothesized that there was a link between gut microbiota and the progression of ICP and characterization of the potential microbiota could go a long way in the prevention and treatment of ICP.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 rRNA region of DNA collected from fecal samples of both diseased and control groups were amplified. 16S rRNA gene amplicon sequencing was then performed on gut microbiota from fecal samples obtained. 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 OTUs (Operational Taxonomic Units) 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; ICP patients and control group and 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 patients with ICP have altered phylogenetic gut microbiota profiles compared to controls, and illustrated that there are significant differences in KEGG pathways.

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