In vivo 1 H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

2019 ◽  
Vol 32 (5) ◽  
pp. e4065 ◽  
Author(s):  
Sanaz Mohajeri ◽  
Tedros Bezabeh ◽  
Omkar B. Ijare ◽  
Scott B. King ◽  
Michael Albert Thomas ◽  
...  
Keyword(s):  
Bile Acid ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Gallbladder Bile ◽  
Human Gallbladder ◽  
Immune Mediated

Altered microbiota and bile acid composition in patients with primary sclerosing cholangitis

2019 ◽  
Author(s):  
T Liwinski ◽  
R Zenouzi ◽  
C John ◽  
H Ehlken ◽  
MC Rühlemann ◽  
...  
Keyword(s):  
Bile Acid ◽  
Primary Sclerosing Cholangitis ◽  
Acid Composition ◽  
Sclerosing Cholangitis

scholarly journals A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

2020 ◽  
Vol 14 (7) ◽  
pp. 935-947 ◽  
Author(s):  
Mohammed Nabil Quraishi ◽  
Animesh Acharjee ◽  
Andrew D Beggs ◽  
Richard Horniblow ◽  
Chris Tselepis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Primary Sclerosing Cholangitis ◽  
Bowel Disease ◽  
Sclerosing Cholangitis ◽  
16S Rrna Analysis ◽  
Immune Infiltration ◽  
Inflammatory Bowel

Abstract Background Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data. Methods Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration. Results The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD. Conclusions Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.

scholarly journals The Effect of Biliary Bile Acid Concentration and Composition on the Calcium Level in Human Gallbladder Bile.

1993 ◽  
Vol 171 (4) ◽  
pp. 297-307 ◽  
Author(s):  
NAOKI TAMASAWA ◽  
MASASHI YONEDA ◽  
ISAO MAKINO ◽  
KAZUO TAKEBE ◽  
KEN SONE ◽  
...  
Keyword(s):  
Bile Acid ◽  
Acid Concentration ◽  
Calcium Level ◽  
Gallbladder Bile ◽  
Human Gallbladder ◽  
Bile Acid Concentration ◽  
Biliary Bile Acid

scholarly journals Alterations of the bile microbiome in primary sclerosing cholangitis

Gut ◽  
2019 ◽  
Vol 69 (4) ◽  
pp. 665-672 ◽  
Author(s):  
Timur Liwinski ◽  
Roman Zenouzi ◽  
Clara John ◽  
Hanno Ehlken ◽  
Malte C Rühlemann ◽  
...  
Keyword(s):  
Bile Acid ◽  
Oral Cavity ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
High Performance ◽  
Alimentary Tract ◽  
Bile Acid Metabolism ◽  
Secondary Bile Acid ◽  
Duodenal Fluid ◽  
Bile Fluid

BackgroundPatients with primary sclerosing cholangitis (PSC) display an altered colonic microbiome compared with healthy controls. However, little is known on the bile duct microbiome and its interplay with bile acid metabolism in PSC.MethodsPatients with PSC (n=43) and controls without sclerosing cholangitis (n=22) requiring endoscopic retrograde cholangiography were included prospectively. Leading indications in controls were sporadic choledocholithiasis and papillary adenoma. A total of 260 biospecimens were collected from the oral cavity, duodenal fluid and mucosa and ductal bile. Microbiomes of the upper alimentary tract and ductal bile were profiled by sequencing the 16S-rRNA-encoding gene (V1–V2). Bile fluid bile acid composition was measured by high-performance liquid chromatography mass spectrometry and validated in an external cohort (n=20).ResultsThe bile fluid harboured a diverse microbiome that was distinct from the oral cavity, the duodenal fluid and duodenal mucosa communities. The upper alimentary tract microbiome differed between PSC patients and controls. However, the strongest differences between PSC patients and controls were observed in the ductal bile fluid, including reduced biodiversity (Shannon entropy, p=0.0127) and increase of pathogen Enterococcus faecalis (FDR=4.18×10−5) in PSC. Enterococcus abundance in ductal bile was strongly correlated with concentration of the noxious secondary bile acid taurolithocholic acid (r=0.60, p=0.0021).ConclusionPSC is characterised by an altered microbiome of the upper alimentary tract and bile ducts. Biliary dysbiosis is linked with increased concentrations of the proinflammatory and potentially cancerogenic agent taurolithocholic acid.

scholarly journals Urisodeoxycholic Acid in Treatment of Liver Cirrhosis

2021 ◽  
Vol 9 (9) ◽  
pp. 1869-1873
Author(s):  
Sangale Mukta
Keyword(s):  
Liver Cirrhosis ◽  
Bile Acid ◽  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Primary Sclerosing Cholangitis ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Biliary Cirrhosis ◽  
Chronic Liver Diseases

Abstract: Ursodeoxycholic acid is a dihy- droxy bile acid with a rapidly expanding spectrum of usage in acute and chronic liver diseases. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholer- esis. Its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis as an adjunct to medical therapy has been well established.Ursodeoxycholic acid prolongs survival in primary biliary cirrhosis and it improves biochemical parameters of cholestasis in various other cholestatic disorders including primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis and total parenteral nutritioninduced cholestasis. However, a positive effect on survival remains to be established in these diseases. Ursodeoxycholic acid is of unproven efficacy in non- cholestatic disorders such as acute rejection after liver transplantation, non-alcoholic steatohepatitis, alcoholic liver disease and chronic viral hepatitis. This review outlines the present knowledge of the Pharmacology of ursodeoxycholic acid, and presents data from clinical trials on its use in chronic liver diseases. Keywords: Liver cirrhosis, Urisodeoxycholic acid

scholarly journals Hepatic versus gallbladder bile composition: in vivo transport physiology of the gallbladder in rainbow trout

2000 ◽  
Vol 278 (6) ◽  
pp. R1674-R1684 ◽  
Author(s):  
M. Grosell ◽  
M. J. O'Donnell ◽  
C. M. Wood
Keyword(s):  
Rainbow Trout ◽  
Bile Acid ◽  
Oncorhynchus Mykiss ◽  
Bile Acids ◽  
Bile Flow ◽  
Gallbladder Bile ◽  
Apical Surface ◽  
Hepatic Bile ◽  
Bile Composition

Ion and water transport across the teleost Oncorhynchus mykiss gallbladder were studied in vivo by comparing flow and composition of hepatic bile, collected by chronic catheter, to volume and composition of terminally collected gallbladder bile. Differences in composition were comparable with those of other vertebrates, whereas bile flow (75 μl ⋅ kg− 1 ⋅ h− 1) was below values reported for endothermic vertebrates. The gallbladder concentrates bile acids five- to sevenfold and exhibits higher net Cl− than Na+ transport in vivo, in contrast to the 1:1 transport ratio from gallbladders under saline/saline conditions. Transepithelial potential (TEP) in the presence of bile, at the apical surface, was −13 mV (bile side negative) but +1.5 mV in the presence of saline. Bile acid in the apical saline reversed the TEP, presumably by a Donnan effect. We propose that ion transport across the gallbladder in vivo involves backflux of Na+ from blood to bile resulting in higher net Cl− than Na+ flux. This Na+backflux is driven by a bile side negative TEP and low Na+activity in bile due to the complexing effects of bile acids.

scholarly journals Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice

2020 ◽  
Vol 21 (22) ◽  
pp. 8874
Author(s):  
Roberta Angioni ◽  
Bianca Calì ◽  
Vasanthy Vigneswara ◽  
Marika Crescenzi ◽  
Ana Merino ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Extracellular Vesicles ◽  
Sclerosing Cholangitis ◽  
Serum Levels ◽  
Portal Triad ◽  
Immune Mediated ◽  
Nfkb Activation ◽  
Effective Therapeutic Strategy ◽  
Progressive Liver Disease ◽  
Clinical Experiments

Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 109 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.

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