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Aberrant gut microbiota alters host bile acid metabolism and contributes to intrahepatic cholestasis of pregnancy

ABSTRACT: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder, which is characterized by raised serum bile acid level and liver transaminases, and adverse fetal outcome. The etiology and mechanism of ICP are complicated and poorly understood, thus therapies have been largely empiric. The gut microbiome differs from the first to the third trimester in healthy pregnant women, and there is a close link between microbial dysbiosis and several pregnancy-related diseases. However, the critical impact of the gut microbiota and its signaling on the regulation of ICP remains elusive. Here, we report that the gut microbiome differed significantly between ICP individuals and healthy controls, and colonization with ICP microbiota was sufficient to induce intrahepatic cholestasis in pregnant mice.

PROVIDER: PRJEB42414 | ENA |

REPOSITORIES: ENA

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Project description:OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse pregnancy outcomes to the mother and fetus. As yet, the metabolic profiles and the association of the clinical features remain obscure.METHODS: Fifty seven healthy pregnant women and 52 patients with ICP were recruited in this study. Plasma samples were obtained from pregnancies who received prenatal care between the 30-36 weeks. Untargeted metabolomics to portray metabolic profiles were performed by LC/MS. Mul- combined with univariate data analysis and statistical analysis were performed to select differential metabolites between ICP and control group. Debiased sparse partial correlation (DSPC) network analysis of differential metabolites was performed to explore the potential mutual regulation among metabolites on the basis of de-sparsified graphical lasso modeling procedure. Pathway analysis was performed using MetaboAnalyst. Linear regression and Pearson correlation analysis were applied to analyze correlations associated with bile acid levels, metabolites, newborn weight and pregnancy outcome in ICP patients.RESULTS: Conspicuous metabolic changes and choreographed metabolic profiles were disclosed: 125 annotated metabolites and eighteen metabolic pathways were disturbed in ICP patients. DSPC networks indicated dense interactions among amino acids and their derivatives, bile acids, carbohydrates and organic acids. The levels of total bile acid were increased in ICP patients with meconium-stained amniotic fluid compared with those without MSAF. Abnormal tryptophan metabolism, elevated long chain saturated fatty acid and estrone sulfate levels, and low antioxidant capacity were relevant to increasing bile acid levels. Correlation analysis showed that newborn body weights were significant correlated with the levels of several bile acids and some metabolites of amino acids.CONCLUSION: The ICP patient showed metabolic disorder, and the levels of a number of metabolites were correlated with TBA levels and neonatal body weights. These results provide us important information to further understand the metabolic characteristics of patients with ICP and adverse pregnancy outcomes.

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Aberrant gut microbiota alters host bile acid metabolism and contributes to intrahepatic cholestasis of pregnancy

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