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.

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Characterization of Gut Microbiota Associated with Clinical Parameters in Intrahepatic Cholestasis of Pregnancy

10.21203/rs.2.18873/v3 ◽

2020 ◽

Author(s):

Rong Li ◽

xuehai chen ◽

Zhongzhen Liu ◽

Yan Chen ◽

Chuan Liu ◽

...

Keyword(s):

Gut Microbiota ◽

Pregnant Women ◽

Intrahepatic Cholestasis ◽

Premature Delivery ◽

Clinical Parameters ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Control Groups ◽

And Control ◽

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 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 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.

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Characterization of Gut Microbiota Associated with Clinical Parameters in Intrahepatic Cholestasis of Pregnancy

10.21203/rs.2.18873/v4 ◽

2020 ◽

Author(s):

Rong Li ◽

xuehai chen ◽

Zhongzhen Liu ◽

Yan Chen ◽

Chuan Liu ◽

...

Keyword(s):

Gut Microbiota ◽

Pregnant Women ◽

Intrahepatic Cholestasis ◽

Premature Delivery ◽

Clinical Parameters ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Control Groups ◽

And Control ◽

Cholestasis Of Pregnancy

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 OTUs (Operational Taxonomic Units) 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.

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

10.21203/rs.2.18873/v2 ◽

2020 ◽

Author(s):

Rong Li ◽

xuehai chen ◽

Zhongzhen Liu ◽

Yan Chen ◽

Chuan Liu ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Pregnant Women ◽

Intrahepatic Cholestasis ◽

Premature Delivery ◽

Clinical Parameters ◽

Control Groups ◽

Fecal Samples ◽

And Control

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

10.21203/rs.2.18873/v1 ◽

2019 ◽

Author(s):

Rong Li ◽

xuehai chen ◽

Zhongzhen Liu ◽

Yan Chen ◽

Chuan Liu ◽

...

Keyword(s):

Gut Microbiota ◽

Pregnant Women ◽

Intrahepatic Cholestasis ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Clinical Parameters ◽

Sequencing Data ◽

Unifrac Distance ◽

Biochemical Indices ◽

And Control

Abstract BackgroundIntrahepatic cholestasis of pregnancy (ICP) is a liver disease that specifically occurs during pregnancy. Pregnant women with ICP biochemically reflect elevated liver functions and increases in serum bilirubin levels, while clinically individuals can display symptoms of itching and have elevated risks of preterm delivery and stillbirths. We hypothesized that there linkages between gut microbiota and ICP progression exist and could be scientifically characterized. MethodsIn total, 27 patients with ICP and 31 unafflicted control patients were recruited in this study. We performed 16S rRNA gene amplicon sequencing on gut microbiota from individual fecal samples. Sequencing data was analyzed and the correlations between components of microbiota and patient ICP status were tested. Relative abundances, related metabolic pathways, and significantly different OTUs between ICP and control patients were identified.ResultsBiochemical indices including measures for bile, ALT, AST, Dbil, and Tbil, and these were found to at higher levels in ICP versus control patients. Gut microbiota in pregnant women was dominated by four major phyla and 27 core genera. PCoA analysis results indicated that there was marginal significant clustering in unweighted Unifrac distance matrices. A moderate correlation coefficient was observed between specific OTUs and measured clinical parameters of patients. When comparing relatively rare microbiota taxa, the abundance of Butyricimonas was lower, while Citrobacter, Pseudomonas, Streptococcus, and Weissella were higher in ICP patients than in control patients. No significant differences in the pathways between ICP and control patients were identified.ConclusionsOur research indicated that patients with ICP have altered phylogenetic gut microbiota profiles compared to control patients without ICP, and that the composition was associated with measurements of patient clinical parameters. These alterations may be correlated with variations of the levels of patient enteric bile acids, and may play a role in the progression of ICP.

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Study On Plasma Exosome Biomarkers Of Pregnant Women With Intrahepatic Cholestasis of Pregnancy

10.21203/rs.3.rs-685401/v1 ◽

2021 ◽

Author(s):

Fan Feng ◽

Mei Jiang ◽

Wei Liu ◽

Di Xu ◽

Xiao-Mei Huang ◽

...

Keyword(s):

Pregnant Women ◽

Roc Curve ◽

Intrahepatic Cholestasis ◽

Protein Concentration ◽

Normal Group ◽

Premature Delivery ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Plasma Samples ◽

Plasma Cluster ◽

Cholestasis Of Pregnancy

Abstract Background：Elevated serum total bile acid level is currently the main index for clinical diagnosis of intrahepatic cholestasis of pregnancy, but the use of TBA as a detection index has certain limitations. The early diagnosis of ICP and new treatment options still need to be further strengthened. Methods: Plasma samples were collected, and exosomes were isolated. Key differential proteins were screened by bioinformatics methods. ELISA method was used to detect the concentration of the key differential protein cluster in plasma samples, and the ROC curve was drawn to find out the best critical value. Results: There were 138 differentially expressed proteins between the ICP group and the normal group by quantitative analysis. Cluster protein was screened as a clinical validation index. The cluster protein concentration of plasma exosomes in the ICP group was significantly higher than that in the normal group (P<0.0001). ROC curve analysis showed that the best critical point for diagnosing ICP according to the plasma exosome cluster protein concentration of pregnant women was 255.28 ng/ml. In the ICP group, the best crucial point for predicting ICP with premature delivery is 286.72 ng/ml. Conclusion: the plasma exosome cluster protein concentration of ICP pregnant women is significantly higher than that of normal pregnant women. When the plasma cluster protein concentration of pregnant women is more remarkable than 255.28ng/ml, ICP can be diagnosed. When the plasma cluster protein concentration of pregnant women is higher than 286.72ng/ml, ICP pregnant women are more likely to have a premature birth.

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Study on Plasma Exosome Biomarkers of Pregnant Women with Intrahepatic Cholestasis of Pregnancy

10.21203/rs.3.rs-685401/v2 ◽

2021 ◽

Author(s):

Fan Feng ◽

Mei Jiang ◽

Wei Liu ◽

Di Xu ◽

Xiao-Mei Huang ◽

...

Keyword(s):

Pregnant Women ◽

Roc Curve ◽

Intrahepatic Cholestasis ◽

Protein Concentration ◽

Normal Group ◽

Premature Delivery ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Plasma Samples ◽

Plasma Cluster ◽

Cholestasis Of Pregnancy

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Association of ABCB4 and ABCB11 nucleotide variants with intrahepatic cholestasis of pregnancy

Journal of Medical Science ◽

10.20883/medical.388 ◽

2019 ◽

Vol 88 (4) ◽

pp. 209-217

Author(s):

Milena Gruszczyńska-Losy ◽

Adrianna Mostowska ◽

Łukasz Adamczak ◽

Paweł Jagodziński ◽

Ewa Wender-Ożegowska ◽

...

Keyword(s):

Pregnant Women ◽

Intrahepatic Cholestasis ◽

Clinical Symptoms ◽

Melting Curve ◽

Liver Disorder ◽

Melting Curve Analysis ◽

Control Group ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Increased Risk ◽

Cholestasis Of Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during gestation. The exact pathogenesis of ICP is multifactorial and still unclear. Therefore, our study aimed to check whether the selected ABCB4and ABCB11nucleotide variants are associated with an increased risk of ICP. Methods:ICP was diagnosed based on clinical symptoms characteristic of this disease and confirmed by increase in serum bile acids and transaminases, spontaneous resolution of clinical symptoms and normalization of laboratory tests after delivery. The total of 86 pregnant women meeting the criteria were included into the study. Healthy pregnant women with uncomplicated pregnancy served as control group (n=310). Sixcommon nucleotide variants in theABCB11and ABCB4genes were genotypedwith the use of high-resolution melting curve analysis. Conclusion:Our study did not show any significant association of analysed ABCB4and ABCB11nucleotide variants with the increased risk of intrahepatic cholestasis of pregnancy.

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