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Background: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP. Methods: We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites. Results: An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP. Conclusions: Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP. [ABSTRACT FROM AUTHOR]

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Aims: To explore the association between thyroid function and gestational diabetes mellitus (GDM) risk in assisted pregnancies.Methods: We screened 57,386 pregnant women treated from February 2013 to October 2017, and 2211 patients were retrospectively enrolled, and their data were analyzed based on quintile groups constituted based on serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels. Odds ratios (ORs) of GDM were analyzed by multivariate logistic regression, adjusted for maternal age and pre-pregnancy body mass index (BMI).Results: The prevalence rate of GDM was 20.1%. Lower FT4 levels were associated with an increased risk of GDM (ORQ2 = 1.512, 95% confidence interval [CI] 1.073-2.132, p = 0.018; ORQ1 = 1.620, 95% CI 1.161-2.261, p = 0.005), but this association disappeared after adjustments. TPOAb+ titer was associated with an increased risk of GDM (aOR = 1.472, 95% CI 1.068-2.028, p = 0.018). Higher TSH (aORQ5 = 2.882, 95% CI 1.919-6.975, p = 0.019) or lower FT4 (aORQ1 = 3.156, 95% CI 1.088-9.115, p = 0.034) levels were associated with an increased risk of GDM in assisted pregnancies for TPOAb+ patients.Conclusion: TPOAb+ is an independent risk factor for GDM in patients with assisted pregnancies. Higher TSH or lower FT4 levels, with TPOAb+ detection, are risk factors for GDM in assisted pregnancies. [ABSTRACT FROM AUTHOR]