Cargando…

Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that is characterized by increased bile acid levels in maternal serum. Studies have shown that cholestatic pregnancy can result in long-term metabolic disturbances in the offspring. However, how ICP shapes the offspring’s im...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Qiong-xi, Huang, Wan-wen, Shen, Wei, Deng, Xiao-shi, Tang, Zi-yu, Chen, Zhen-hui, Zhao, Wei, Fan, Hong-ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234109/
https://www.ncbi.nlm.nih.gov/pubmed/35769469
http://dx.doi.org/10.3389/fimmu.2022.889646
_version_ 1784735982635974656
author Lin, Qiong-xi
Huang, Wan-wen
Shen, Wei
Deng, Xiao-shi
Tang, Zi-yu
Chen, Zhen-hui
Zhao, Wei
Fan, Hong-ying
author_facet Lin, Qiong-xi
Huang, Wan-wen
Shen, Wei
Deng, Xiao-shi
Tang, Zi-yu
Chen, Zhen-hui
Zhao, Wei
Fan, Hong-ying
author_sort Lin, Qiong-xi
collection PubMed
description Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that is characterized by increased bile acid levels in maternal serum. Studies have shown that cholestatic pregnancy can result in long-term metabolic disturbances in the offspring. However, how ICP shapes the offspring’s immunity and predisposition to inflammatory disorders at an early stage is unknown. In this study, we investigated the effect of maternal cholestasis on neonatal offspring metabolism and immune function. We compared 71 neonates with ICP mothers and 63 neonates with healthy mothers and found that the incidence of jaundice and infection was significantly higher in ICP offspring. Maternal serum total bile acid level was associated with blood cell counts in full-term ICP offspring. In animal experiments, a compensatory activation of hepatic and ileal farnesoid X receptor (FXR) and altered gut microbiota in the first week were found in ICP offspring. We also investigated lipopolysaccharide (LPS)-induced inflammatory responses in neonatal rats and found that ICP offspring were more susceptible to inflammation. To understand the correlation between congenital abnormal FXR activation and tissue immunity dysregulation, we assessed the effects of the FXR agonist GW4064 and FXR antagonist E/Z-GS in ICP offspring after LPS exposure. The expression of several pro-inflammatory cytokines significantly decreased after treatment with E/Z-GS but increased after treatment with GW4064. Treatment with the probiotic Lactobacillus rhamnosus LRX01 that inhibits FXR expression in the ileum reduced susceptibility to LPS exposure in ICP offspring. The current study indicated that cholestatic pregnancy may increase the susceptibility of the offspring to inflammation by altering bile acid metabolism and gut microbiota at an early stage. We suggest that supplementation with Lactobacillus rhamnosus LRX01, which inhibits FXR expression in the ileum, may improve intestinal immunity in ICP offspring.
format Online
Article
Text
id pubmed-9234109
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92341092022-06-28 Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota Lin, Qiong-xi Huang, Wan-wen Shen, Wei Deng, Xiao-shi Tang, Zi-yu Chen, Zhen-hui Zhao, Wei Fan, Hong-ying Front Immunol Immunology Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that is characterized by increased bile acid levels in maternal serum. Studies have shown that cholestatic pregnancy can result in long-term metabolic disturbances in the offspring. However, how ICP shapes the offspring’s immunity and predisposition to inflammatory disorders at an early stage is unknown. In this study, we investigated the effect of maternal cholestasis on neonatal offspring metabolism and immune function. We compared 71 neonates with ICP mothers and 63 neonates with healthy mothers and found that the incidence of jaundice and infection was significantly higher in ICP offspring. Maternal serum total bile acid level was associated with blood cell counts in full-term ICP offspring. In animal experiments, a compensatory activation of hepatic and ileal farnesoid X receptor (FXR) and altered gut microbiota in the first week were found in ICP offspring. We also investigated lipopolysaccharide (LPS)-induced inflammatory responses in neonatal rats and found that ICP offspring were more susceptible to inflammation. To understand the correlation between congenital abnormal FXR activation and tissue immunity dysregulation, we assessed the effects of the FXR agonist GW4064 and FXR antagonist E/Z-GS in ICP offspring after LPS exposure. The expression of several pro-inflammatory cytokines significantly decreased after treatment with E/Z-GS but increased after treatment with GW4064. Treatment with the probiotic Lactobacillus rhamnosus LRX01 that inhibits FXR expression in the ileum reduced susceptibility to LPS exposure in ICP offspring. The current study indicated that cholestatic pregnancy may increase the susceptibility of the offspring to inflammation by altering bile acid metabolism and gut microbiota at an early stage. We suggest that supplementation with Lactobacillus rhamnosus LRX01, which inhibits FXR expression in the ileum, may improve intestinal immunity in ICP offspring. Frontiers Media S.A. 2022-06-13 /pmc/articles/PMC9234109/ /pubmed/35769469 http://dx.doi.org/10.3389/fimmu.2022.889646 Text en Copyright © 2022 Lin, Huang, Shen, Deng, Tang, Chen, Zhao and Fan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lin, Qiong-xi
Huang, Wan-wen
Shen, Wei
Deng, Xiao-shi
Tang, Zi-yu
Chen, Zhen-hui
Zhao, Wei
Fan, Hong-ying
Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota
title Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota
title_full Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota
title_fullStr Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota
title_full_unstemmed Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota
title_short Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota
title_sort intrahepatic cholestasis of pregnancy increases inflammatory susceptibility in neonatal offspring by modulating gut microbiota
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234109/
https://www.ncbi.nlm.nih.gov/pubmed/35769469
http://dx.doi.org/10.3389/fimmu.2022.889646
work_keys_str_mv AT linqiongxi intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota
AT huangwanwen intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota
AT shenwei intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota
AT dengxiaoshi intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota
AT tangziyu intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota
AT chenzhenhui intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota
AT zhaowei intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota
AT fanhongying intrahepaticcholestasisofpregnancyincreasesinflammatorysusceptibilityinneonataloffspringbymodulatinggutmicrobiota