Background And Purpose: Ursodeoxycholic acid (UDCA) is the first-line treatment for primary biliary cholangitis, but its effects on the enterohepatic circulation of bile acid (BA) have been under-investigated. Therefore, we studied the influence of UDCA on BA enterohepatic circulation in vivo and the mechanisms by which UDCA affects the BA kinetics.
Experimental Approach: Mice were treated with UDCA and other BAs to observe changes in BA pool and BA transporters involved in enterohepatic circulation. Isotope dilution techniques and biochemical analyses were applied to study BA kinetics after oral administration of UDCA, and the mechanism involved.
Key Results: Oral administration of UDCA in mice reduced the overall BA pool and produced a unique BA profile with high-abundance conjugated UDCA species, including tauroursodeoxycholic acid (TUDCA) and GUDCA. We found increased expression of several main BA transporters in the ileum and liver. BA kinetic experiment showed that feeding UDCA shortened cycling time of BA and accelerated BA enterohepatic circulation. Additionally, we found evidence that the effect of UDCA administration on accelerating BA enterohepatic circulation was due to the inhibition of farnesoid X receptor (FXR) signalling in the ileum and FGF15/19 in the liver.
Conclusion And Implications: Oral administration of UDCA produced a unique BA profile with high-abundance TUDCA and GUDCA and significantly accelerated BA enterohepatic circulation through the inhibition of intestinal FXR signalling and reduced level of FGF15/19, which in turn, induced the expression of BA transporters in the liver. These findings highlight a critical role for UDCA in maintaining the homeostasis of BA enterohepatic circulation in vivo.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637225 | PMC |
| http://dx.doi.org/10.1111/bph.14705 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chronic Cr(VI) exposure-induced biotoxicity involved in liver microbiota-gut axis disruption in Phoxinus lagowskii Dybowski based on multi-omics technologies.
Environ Pollut
January 2025
Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China. Electronic address:
Cr(VI) is widely used in industry and has high toxicity, making it one of the most common environmental pollutants. Long-term exposure to Cr(VI) can cause metabolic disorders and tissue damage. However, the effects of Cr(VI) on liver and gut microbes in fish have rarely been reported.
View Article and Find Full Text PDFAdvances in dietary polyphenols: Regulation of inflammatory bowel disease (IBD) via bile acid metabolism and the gut-brain axis.
Food Chem
January 2025
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, Zhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and Engineering, Ningbo University, Ningbo, Zhejiang, China. Electronic address:
Article Synopsis
- Dietary polyphenols are plant compounds with potential health benefits, particularly in preventing and treating chronic diseases like Inflammatory Bowel Disease (IBD).
- Despite their promise, research is hindered by challenges in analyzing their structure and limitations of current models.
- This review highlights the interactions between dietary polyphenols, bile acids, gut microbiota, and the gut-brain axis, paving the way for better understanding and future research in their therapeutic roles.
Visualizing enterohepatic circulation in vivo by sensitive F MRI with a fluorinated ferrous chelate-based small molecule probe.
Biomaterials
January 2025
The Key Laboratory for Chemical Biology of Fujian Province, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China; Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen Key Laboratory of Translational Medical of Digestive System Tumor, Zhongshan Hospital, Xiamen University, Xiamen 361004, China. Electronic address:
Enterohepatic circulation (EHC) is a critical biological process for the normal regulation of many endogenous biomolecules and the increased retention of various exogenous substances. The status of EHC is closely related to the ordinary functioning of several digestive organs. However, it remains a challenge to achieve in vivo real-time visualization of this process.
View Article and Find Full Text PDFEffects of Metabolites Derived from Guava ( L.) Leaf Extract Fermented by on Hepatic Energy Metabolism via SIRT1-PGC1α Signaling in Diabetic Mice.
Nutrients
December 2024
Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea.
Background/objectives: Type 2 diabetes mellitus (T2DM) is considered a serious risk to public health since its prevalence is rapidly increasing worldwide despite numerous therapeutics. Insulin resistance in T2DM contributes to chronic inflammation and other metabolic abnormalities that generate fat accumulation in the liver, eventually leading to the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Recently, the possibility that microbial-derived metabolites may alleviate MAFLD through enterohepatic circulation has emerged, but the underlying mechanism remains unclear.
View Article and Find Full Text PDFExploring the effects of gut microbiota on cholangiocarcinoma progression by patient-derived organoids.
J Transl Med
January 2025
Department of Psychiatry and Psychotherapy, University Medical Center Mainz, 55131, Mainz, Germany.
Background: Recent research indicates a role of gut microbiota in development and progression of life-threatening diseases such as cancer. Carcinomas of the biliary ducts, the so-called cholangiocarcinomas, are known for their aggressive tumor biology, implying poor prognosis of affected patients. An impact of the gut microbiota on cholangiocarcinoma development and progression is plausible due to the enterohepatic circulation and is therefore the subject of scientific debate, however evidence is still lacking.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!