scholarly journals β-Catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis

Hepatology ◽  
2018 ◽  
Vol 67 (3) ◽  
pp. 955-971 ◽  
Author(s):  
Michael D. Thompson ◽  
Akshata Moghe ◽  
Pamela Cornuet ◽  
Rebecca Marino ◽  
Jianmin Tian ◽  
...  
Keyword(s):  
Bile Acid ◽  
Acid Metabolism ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Receptor Signaling

Lactoferrin promotes bile acid metabolism and reduces hepatic cholesterol deposition by inhibiting the farnesoid X receptor (FXR)-mediated enterohepatic axis

2019 ◽  
Vol 10 (11) ◽  
pp. 7299-7307 ◽  
Author(s):  
Chen-Jie Ling ◽  
Jia-Ying Xu ◽  
Yun-Hong Li ◽  
Xing Tong ◽  
Huan-Huan Yang ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Bile Acid ◽  
Acid Metabolism ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Hepatic Cholesterol ◽  
Reduce Body Weight ◽  
Regulate Lipid Metabolism

Lactoferrin (LF) is a multifunctional glycoprotein that can regulate lipid metabolism, lower cholesterol, reduce body weight, and prevent atherosclerosis.

scholarly journals Effects of Rhein on Bile Acid Homeostasis in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhong Xian ◽  
Jingzhuo Tian ◽  
Lianmei Wang ◽  
Yushi Zhang ◽  
Jiayin Han ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Edible Plant ◽  
Clinical Dose ◽  
Acid Accumulation ◽  
Liver And Kidney ◽  
Hepatic Transporters

Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice. However, the effects of repeated intake of rhein on liver function and bile acid metabolism are rarely reported. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered with rhein for 5 weeks. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), and bile salt export pump (BSEP) mRNA, and upregulated the expression of (cholesterol 7α-hydroxylase) CYP7A1 mRNA. Rhein close to the clinical dose (10 mg/kg and 30 mg/kg) reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. These results denote that rhein is relatively safe to use at a reasonable dose and timing. 30 mg/kg rhein may promote bile acid transport and reduce bile acid accumulation by upregulating the expression of FXR mRNA and Mrp3 mRNA, potentially resulting in the decrease in serum UBCAs.

scholarly journals The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

2021 ◽  
Vol 14 ◽  
pp. 175628482110177
Author(s):  
Benjamin H. Mullish ◽  
Jessica R. Allegretti
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Gut Microbiome ◽  
Acid Metabolism ◽  
Disease Process ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Clostridioides Difficile ◽  
Gut Barrier Function ◽  
Clostridioides Difficile Infection

Clostridioides difficile infection (CDI) remains a major global cause of gastrointestinal infection, with significant associated morbidity, mortality and impact upon healthcare system resources. Recent antibiotic use is a key risk factor for the condition, with the marked antibiotic-mediated perturbations in gut microbiome diversity and composition that underpin the pathogenesis of CDI being well-recognised. However, only relatively recently has further insight been gained into the specific mechanistic links between these gut microbiome changes and CDI, with alteration of gut microbial metabolites – in particular, bile acid metabolism – being a particular area of focus. A variety of in vitro, ex vivo, animal model and human studies have now demonstrated that loss of gut microbiome members with bile-metabolising capacity (including bile salt hydrolases, and 7-α-dehydroxylase) – with a resulting alteration of the gut bile acid milieu – contributes significantly to the disease process in CDI. More specifically, this microbiome disruption results in the enrichment of primary conjugated bile acids (including taurocholic acid, which promotes the germination of C. difficile spores) and loss of secondary bile acids (which inhibit the growth of C. difficile, and may bind to and limit activity of toxins produced by C. difficile). These bile acid changes are also associated with reduced activity of the farnesoid X receptor pathway, which may exacerbate C. difficile colitis throughout its impact upon gut barrier function and host immune/inflammatory response. Furthermore, a key mechanism of efficacy of faecal microbiota transplant (FMT) in treating recurrent CDI has been shown to be restoration of gut microbiome bile metabolising functionality; ensuring the presence of this functionality among defined microbial communities (and other ‘next generation’ FMT products) designed to treat CDI may be critical to their success.

scholarly journals Modulation of Bile Acid Metabolism to Improve Plasma Lipid and Lipoprotein Profiles

2021 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Boyan Zhang ◽  
Folkert Kuipers ◽  
Jan Freark de de Boer ◽  
Jan Albert Kuivenhoven
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Ldl Cholesterol ◽  
Farnesoid X Receptor ◽  
New Drugs ◽  
Bile Acid Metabolism ◽  
Atherosclerotic Cardiovascular Disease ◽  
Faecal Excretion ◽  
Alcoholic Fatty Liver

New drugs targeting bile acid metabolism are currently being evaluated in clinical studies for their potential to treat cholestatic liver diseases, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Changes in bile acid metabolism, however, translate into an alteration of plasma cholesterol and triglyceride concentrations, which may also affect cardiovascular outcomes in such patients. This review attempts to gain insight into this matter and improve our understanding of the interactions between bile acid and lipid metabolism. Bile acid sequestrants (BAS), which bind bile acids in the intestine and promote their faecal excretion, have long been used in the clinic to reduce LDL cholesterol and, thereby, atherosclerotic cardiovascular disease (ASCVD) risk. However, BAS modestly but consistently increase plasma triglycerides, which is considered a causal risk factor for ASCVD. Like BAS, inhibitors of the apical sodium-dependent bile acid transporter (ASBTi’s) reduce intestinal bile acid absorption. ASBTi’s show effects that are quite similar to those obtained with BAS, which is anticipated when considering that accelerated faecal loss of bile acids is compensated by an increased hepatic synthesis of bile acids from cholesterol. Oppositely, treatment with farnesoid X receptor agonists, resulting in inhibition of bile acid synthesis, appears to be associated with increased LDL cholesterol. In conclusion, the increasing efforts to employ drugs that intervene in bile acid metabolism and signalling pathways for the treatment of metabolic diseases such as NAFLD warrants reinforcing interactions between the bile acid and lipid and lipoprotein research fields. This review may be considered as the first step in this process.

scholarly journals P054 Modulation of the Gut Microbiota-Farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S161-S161
Author(s):  
M Xu ◽  
Y Shen ◽  
M Cen
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Acid Metabolism ◽  
Deoxycholic Acid ◽  
Intestinal Inflammation ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Gut Dysbiosis ◽  
Rdna Sequencing

Abstract Background Inflammatory bowel disease (IBD) is associated with gut dysbiosis and dysregulation of bile acid metabolism. A high luminal content of deoxycholic acid (DCA) with consumption of a Westernized diet is implicated in the pathogenesis of IBD. The aim of the study is to explore the role of intestinal microbiota and bile acid metabolism in mice with DCA-induced intestinal inflammation. Methods 4-week-old wild-type C57BL mice were fed with AIN-93G (control diet), AIN-93G+0.2% DCA, AIN-93G+0.2% DCA+6 weeks of fexaramine (FXR agonist), or AIN-93G+0.2% DCA+antibiotic cocktail for 24 weeks. Histopathology, Western blotting, and qPCR were performed on the intestinal tissue. Fecal microbiota was analyzed by 16S rDNA sequencing. Fecal bile acid and short-chain fatty acid (SCFA) levels were analyzed by chromatography. Results Gut dysbiosis and enlarged bile acid pool were observed in DCA-treated mice, accompanied by a lower farnesoid X receptor (FXR) activity in the intestine. Administration of fexaramine mitigated DCA-induced intestinal injury, restored intestinal FXR activity, activated fibroblast growth factor 15, and normalized bile acid metabolism. Furthermore, fexaramine administration increased the abundance of SCFA-producing bacteria. Depletion of the commensal microbiota with antibiotics decreased the diversity of the intestinal microbiota, attenuated bile acid synthesis, and reduced intestinal inflammation induced by DCA. Conclusion DCA induced-intestinal inflammation is associated with alterations of gut microbiota and bile acid profiles. Interventions targeting the gut microbiota-FXR signaling pathway may reduce DCA-induced intestinal disease.

scholarly journals Gut Dysbiosis and Abnormal Bile Acid Metabolism in Colitis-Associated Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Li Liu ◽  
Min Yang ◽  
Wenxiao Dong ◽  
Tianyu Liu ◽  
Xueli Song ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Farnesoid X Receptor ◽  
Mucosal Barrier ◽  
Bile Acid Metabolism ◽  
Preventive Strategy ◽  
Gut Dysbiosis ◽  
Bile Acid Receptors

Background. Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. Methods. C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. Results. The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. Conclusion. Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.

Dynamics of the enterohepatic circulation of bile acids in healthy humans

2021 ◽  
Author(s):  
Frans Stellaard ◽  
Dieter Lütjohann
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Enterohepatic Circulation ◽  
Feedback Inhibition ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Healthy Humans

Regulation of bile acid metabolism is normally discussed as the regulation of bile acid synthesis, which serves to compensate for intestinal loss in order to maintain a constant pool size. After a meal, bile acids start cycling in the enterohepatic circulation. Farnesoid X receptor-dependent ileal and hepatic processes lead to negative feedback inhibition of bile acid synthesis. When the intestinal bile acid flux decreases, the inhibition of synthesis is released. The degree of inhibition of synthesis and the mechanism and degree of activation are still unknown. Moreover, in humans, a biphasic diurnal expression pattern of bile acid synthesis has been documented, indicating maximal synthesis around 3 pm and 9 pm. Quantitative data on the hourly synthesis schedule as compensation for intestinal loss are lacking. In this review, we describe the classical view on bile acid metabolism and present alternative concepts that are based on the overlooked feature that bile acids transit through the enterohepatic circulation very rapidly. A daily profile of the cycling and total bile acid pool sizes and potential controlled and uncontrolled mechanisms for synthesis are predicted. It remains to be elucidated by which mechanism clock genes interact with the Farnesoid X receptor-controlled regulation of bile acid synthesis. This mechanism could become an attractive target to enhance bile acid synthesis at night, when cholesterol synthesis is high, thus lowering serum LDL-cholesterol.

Sign in / Sign up

Export Citation Format

Share Document