Profiles and Integration of the Gut Microbiome and Fecal Metabolites in Severe Intrahepatic Cholestasis of Pregnancy

Overview

Journal BMC Microbiol

Publisher Biomed Central

Specialty Microbiology

Date 2023 Oct 2

PMID 37784030

Authors

Xiang Li

Han Xie

Jia-Jing Chao

Yuan-Hui Jia

Jia Zuo

Yan-Peng An

Yi-Rong Bao

Xiang Jiang

Hao Ying

Affiliations

Soon will be listed here.

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.

Citing Articles

Association between ABCB4 variants and intrahepatic cholestasis of pregnancy.

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Genetically Predicted Gut Microbiota Mediate the Association Between Fatty Acids and Intrahepatic Cholestasis of Pregnancy: A Mendelian Randomization Analysis.

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Pregnancy cholestasis typically occurs in the third trimester of pregnancy and is a significant clinical condition.

Kucukyurt A, Atakul N, Solak Y Arch Gynecol Obstet. 2024; 310(5):2531-2539.

PMID: 39352541 DOI: 10.1007/s00404-024-07736-3.

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