Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy
Abstract 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...
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2023-10-01
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Online Access: | https://doi.org/10.1186/s12866-023-02983-x |
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author | Xiang Li Han Xie Jia-jing Chao Yuan-Hui Jia Jia Zuo Yan-peng An Yi-Rong Bao Xiang Jiang Hao Ying |
author_facet | Xiang Li Han Xie Jia-jing Chao Yuan-Hui Jia Jia Zuo Yan-peng An Yi-Rong Bao Xiang Jiang Hao Ying |
author_sort | Xiang Li |
collection | DOAJ |
description | Abstract 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. |
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spelling | doaj.art-748bcc783ea84f139d0e6f9adeb4b8ee2023-11-19T12:32:44ZengBMCBMC Microbiology1471-21802023-10-0123111210.1186/s12866-023-02983-xProfiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancyXiang Li0Han Xie1Jia-jing Chao2Yuan-Hui Jia3Jia Zuo4Yan-peng An5Yi-Rong Bao6Xiang Jiang7Hao Ying8Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan UniversityShanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyAbstract 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.https://doi.org/10.1186/s12866-023-02983-xIntrahepatic cholestasis of pregnancyBile acidGut microbiome16S rRNAMetabolomicsMIMOSA model |
spellingShingle | Xiang Li Han Xie Jia-jing Chao Yuan-Hui Jia Jia Zuo Yan-peng An Yi-Rong Bao Xiang Jiang Hao Ying Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy BMC Microbiology Intrahepatic cholestasis of pregnancy Bile acid Gut microbiome 16S rRNA Metabolomics MIMOSA model |
title | Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy |
title_full | Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy |
title_fullStr | Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy |
title_full_unstemmed | Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy |
title_short | Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy |
title_sort | profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy |
topic | Intrahepatic cholestasis of pregnancy Bile acid Gut microbiome 16S rRNA Metabolomics MIMOSA model |
url | https://doi.org/10.1186/s12866-023-02983-x |
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