Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks

Bile acids (BAs) are critical mediators of metabolic and immune regulation, influencing both liver and intestinal function. Their homeostasis, maintained through the enterohepatic circulation, is pivotal for immune-metabolic balance. BAs activate key receptors, including Farnesoid X Receptor (FXR) a...

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Main Authors: Wenlong Yan, Kun Zhang, Jing Guo, Lingfen Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595486/full
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author Wenlong Yan
Kun Zhang
Kun Zhang
Jing Guo
Lingfen Xu
author_facet Wenlong Yan
Kun Zhang
Kun Zhang
Jing Guo
Lingfen Xu
author_sort Wenlong Yan
collection DOAJ
description Bile acids (BAs) are critical mediators of metabolic and immune regulation, influencing both liver and intestinal function. Their homeostasis, maintained through the enterohepatic circulation, is pivotal for immune-metabolic balance. BAs activate key receptors, including Farnesoid X Receptor (FXR) and TGR5, to modulate inflammation. FXR exerts anti-inflammatory effects by suppressing NF-κB signaling and cytokine production, whereas TGR5 primarily regulates NLRP3 inflammasome activation. Dysregulated BA signaling, driven by microbial dysbiosis, exacerbates inflammatory diseases like non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD). This review explores the intricate roles of BAs in inflammation, highlighting the microbiome’s influence on BA metabolism and immune responses. Understanding the BA-immune axis offers new therapeutic avenues for modulating inflammation and improving clinical outcomes in inflammatory diseases.
format Article
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institution DOAJ
issn 1664-3224
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-4bae9ef4dcbe4b2e964fed77c69a1bb42025-08-20T03:07:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15954861595486Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networksWenlong Yan0Kun Zhang1Kun Zhang2Jing Guo3Lingfen Xu4Department of Pediatrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, ChinaDepartment of Pediatrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, ChinaThe Center for Pediatric Liver Diseases, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Pediatrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, ChinaDepartment of Pediatrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, ChinaBile acids (BAs) are critical mediators of metabolic and immune regulation, influencing both liver and intestinal function. Their homeostasis, maintained through the enterohepatic circulation, is pivotal for immune-metabolic balance. BAs activate key receptors, including Farnesoid X Receptor (FXR) and TGR5, to modulate inflammation. FXR exerts anti-inflammatory effects by suppressing NF-κB signaling and cytokine production, whereas TGR5 primarily regulates NLRP3 inflammasome activation. Dysregulated BA signaling, driven by microbial dysbiosis, exacerbates inflammatory diseases like non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD). This review explores the intricate roles of BAs in inflammation, highlighting the microbiome’s influence on BA metabolism and immune responses. Understanding the BA-immune axis offers new therapeutic avenues for modulating inflammation and improving clinical outcomes in inflammatory diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595486/fullbile acid metabolismgut-liver axisFXRTGR5inflammatory networkintestinal flora
spellingShingle Wenlong Yan
Kun Zhang
Kun Zhang
Jing Guo
Lingfen Xu
Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks
Frontiers in Immunology
bile acid metabolism
gut-liver axis
FXR
TGR5
inflammatory network
intestinal flora
title Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks
title_full Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks
title_fullStr Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks
title_full_unstemmed Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks
title_short Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks
title_sort bile acid mediated gut liver axis crosstalk the role of nuclear receptor signaling in dynamic regulation of inflammatory networks
topic bile acid metabolism
gut-liver axis
FXR
TGR5
inflammatory network
intestinal flora
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595486/full
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AT kunzhang bileacidmediatedgutliveraxiscrosstalktheroleofnuclearreceptorsignalingindynamicregulationofinflammatorynetworks
AT jingguo bileacidmediatedgutliveraxiscrosstalktheroleofnuclearreceptorsignalingindynamicregulationofinflammatorynetworks
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