Related Experiment Video
Updated: Dec 21, 2025
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Intestinal Inflammation Alters the Expression of Hepatic Bile Acid Receptors Causing Liver Impairment
Anna Negroni1, Noemi Fiaschini2,3, Francesca Palone2
1Division of Health Protection Technologies, ENEA.
Objectives:
The gut-liver axis has been recently investigated in depth in relation to intestinal and hepatic diseases. Key actors are bile acid (BA) receptors, as farnesoid-X-receptor (FXR), pregnane-X-receptor (PXR), and G-protein-coupled-receptor (GPCR; TGR5), that control a broad range of metabolic processes as well as inflammation and fibrosis. The present study aims to investigate the impact of intestinal inflammation on liver health with a focus on FXR, PXR, and TGR5 expression. The strategy to improve liver health by reducing gut inflammation is also considered. Modulation of BA receptors in the inflamed colonic tissues of inflammatory bowel disease (IBD) pediatric patients is analyzed.
Methods:
A dextran sodium sulphate (DSS) colitis animal model was built. Co-cultures with Caco2 and HepG2 cell lines were set up. Modulation of BA receptors in biopsies of IBD pediatric patients was assessed by real-time PCR and immunohistochemistry.
Results:
Histology showed inflammatory cell infiltration in the liver of DSS mice, where FXR and PXR were significantly decreased and oxidative stress was increased. Exposure of Caco2 to inflammatory stimuli resulted in the reduction of BA receptor expression in HepG2. Caco2 treatment with dipotassium glycyrrhizate (DPG) reduced these effects on liver cells. Inflamed colon of patients showed altered FXR, PXR, and TGR5 expression.
Conclusions:
This study strongly suggests that gut inflammation affects hepatic cells by altering BA receptor levels as well as increasing the production of pro-inflammatory cytokines and oxidative stress. Hence, reducing gut inflammation is needed not only to improve the intestinal disease but also to protect the liver.
Insights
Gut inflammation negatively impacts liver health by altering bile acid (BA) receptors, including farnesoid-X-receptor (FXR) and pregnane-X-receptor (PXR). Reducing gut inflammation is crucial for protecting liver function and improving intestinal diseases.
Area of Science:
- Gastroenterology and Hepatology
- Immunology
- Molecular Biology
Background:
- The gut-liver axis plays a critical role in maintaining metabolic homeostasis and is implicated in various intestinal and hepatic diseases.
- Bile acid (BA) receptors, such as farnesoid-X-receptor (FXR), pregnane-X-receptor (PXR), and G-protein-coupled-receptor (GPCR; TGR5), are key regulators of metabolic processes, inflammation, and fibrosis.
- Intestinal inflammation is increasingly recognized as a significant factor influencing liver health.
Purpose of the Study:
- To investigate the impact of intestinal inflammation on liver health, specifically examining the expression of FXR, PXR, and TGR5.
- To explore strategies for improving liver health by mitigating gut inflammation.
- To analyze the modulation of BA receptors in pediatric inflammatory bowel disease (IBD) patients with inflamed colonic tissues.
Main Methods:
- Establishment of a dextran sodium sulphate (DSS)-induced colitis animal model.
- Utilizing co-culture systems with Caco2 (intestinal) and HepG2 (hepatic) cell lines.
- Assessment of BA receptor expression in colonic biopsies from pediatric IBD patients using real-time PCR and immunohistochemistry.
Main Results:
- DSS-induced colitis in mice led to liver inflammatory cell infiltration, decreased FXR and PXR expression, and increased oxidative stress.
- Inflammatory stimuli in Caco2 cells reduced BA receptor expression in co-cultured HepG2 cells.
- Dipotassium glycyrrhizate (DPG) treatment mitigated the negative effects on liver cells.
- Altered expression of FXR, PXR, and TGR5 was observed in the inflamed colons of IBD patients.
Conclusions:
- Gut inflammation adversely affects hepatic cells by altering BA receptor levels and promoting pro-inflammatory cytokine production and oxidative stress.
- Reducing intestinal inflammation is essential for both managing intestinal diseases and safeguarding liver health.
- Targeting BA receptors and gut inflammation presents a potential therapeutic strategy for gut-liver axis disorders.
More Related Videos
Related Concept Videos
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
01:25Factors Influencing Drug Absorption: Disease States and Pharmacology
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test