Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids

Cholesterol gallstone (CG) disease has relationships with several metabolic abnormalities. Astragalus polysaccharides (APS) have been shown to have multiple benefits against metabolic disorders. We attempted to uncover the effect and mechanism of action of APS on diet-induced CG formation in mice. Animals were fed a chow diet or lithogenic diet (LD) with or without APS supplementation. The effect of APS on CG formation was evaluated. The level of individual bile acids (BAs) in gallbladder bile and ileum were measured by liquid chromatography-tandem mass spectrometry. Real-time reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess expression of the genes involved in BA metabolism and the enterohepatic circulation. Cecal contents were collected to characterize microbiota profiles. APS ameliorated LD-induced CG formation in mice. APS reduced the level of total cholesterol, bile acid hydrophobicity index and cholesterol saturation index in gallbladder bile. The protective effect of APS might result from reduced absorption of cholic acid in the intestine and increased hepatic BA synthesis. APS relieved the LD-induced activation of the intestinal farnesoid X receptor and decreased ileal expression of fibroblast growth factor 15. In the liver, expression of cytochrome P450 (Cyp) enzyme Cyp7a1 and Cyp7b1 was increased, whereas expression of adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8 was decreased by APS. APS improved the diversity of the gut microbiota and increased the relative abundance of the Bacteroidetes phylum. APS had demonstratable benefits against CG disease, which might be associated with enhanced BA synthesis and improved gut microbiota. Our results suggest that APS may be a potential strategy for the prevention of CG disease.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.6.r1674 ◽

2000 ◽

Vol 278 (6) ◽

pp. R1674-R1684 ◽

Cited By ~ 13

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.

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Effect of twice-daily oral administration of hydrocortisone on the bile acids composition of gallbladder bile in dogs

American Journal of Veterinary Research ◽

10.2460/ajvr.72.12.1607 ◽

2011 ◽

Vol 72 (12) ◽

pp. 1607-1612 ◽

Cited By ~ 13

Author(s):

Peter H. Kook ◽

Stefan Schellenberg ◽

Katharina M. Rentsch ◽

Claudia E. Reusch ◽

Tony M. Glaus

Keyword(s):

Oral Administration ◽

Bile Acids ◽

Gallbladder Bile ◽

Daily Oral Administration

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DIFFERENTIAL ANALYSIS OF BILE ACIDS IN HUMAN GALLBLADDER BILE

Archives of Surgery ◽

10.1001/archsurg.1936.01190060003001 ◽

1936 ◽

Vol 33 (6) ◽

pp. 913 ◽

Cited By ~ 12

Author(s):

RALPH COLP

Keyword(s):

Bile Acids ◽

Gallbladder Bile ◽

Differential Analysis ◽

Human Gallbladder

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The effect of cholesterol feeding on gallbladder bile acids of the rabbit. Evidence that lithocholic acid is a primary bile acid in the rabbit

Biochemical Journal ◽

10.1042/bj1980639 ◽

1981 ◽

Vol 198 (3) ◽

pp. 639-643 ◽

Cited By ~ 4

Author(s):

W Taylor ◽

W R Ellis ◽

G D Bell

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Lithocholic Acid ◽

Alternative Pathway ◽

Normal Diet ◽

Gallbladder Bile ◽

Gas Chromatography Mass Spectrometry ◽

Alpha 7 ◽

Total Bile Acids ◽

Primary Bile Acid

The bile acid in gallbladder bile of rabbits fed a normal diet or one containing 2% (w/w) cholesterol have been determined by gas chromatography-mass spectrometry. The predominant bile acids in normally fed rabbits were 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholan-24-oic acid (cholic acid), 3 alpha, 12 alpha-dihydroxy-5 alpha-cholan-24-oic acid (allodeoxycholic acid) and 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid (deoxycholic acid) with very much smaller amounts of 3 alpha-hydroxy-5 beta-cholan-24-oic acid (lithocholic acid) and 3 alpha, 12 beta-dihydroxy-5 beta-cholan-24-oic acid. In the cholesterol-fed animals the lithocholate became a predominant bile acid. Sulphated bile acids accounted for less than 1% of the total bile acids. It is proposed that lithocholic acid may be a primary bile acid in the cholesterol-fed rabbit, formed by an alternative pathway of biosynthesis involving hepatic mitochondria.

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Conjugated Bile Acids in Gallbladder Bile and Serum as Potential Biomarkers for Cholesterol Polyps and Adenomatous Polyps

The International Journal of Biological Markers ◽

10.5301/jbm.5000173 ◽

2016 ◽

Vol 31 (1) ◽

pp. 73-79 ◽

Cited By ~ 5

Author(s):

Mei-Fen Zhao ◽

Peng Huang ◽

Chun-Lin Ge ◽

Tao Sun ◽

Zhi-Gang Ma ◽

...

Keyword(s):

Bile Acids ◽

High Performance ◽

Gallbladder Bile ◽

Adenomatous Polyps ◽

Control Group ◽

Serum Samples ◽

Diagnostic Efficacy ◽

Glycocholic Acid ◽

Bile Samples ◽

Conjugated Bile Acids

Purpose To identify conjugated bile acids in gallbladder bile and serum as possible biomarkers for cholesterol polyps (CPs) and adenomatous polyps (APs). Methods Gallbladder bile samples and serum samples were collected from 18 patients with CPs (CP group), 9 patients with APs (AP group), and 20 patients with gallstones (control group) from March to November, 2013. High performance liquid chromatography (HPLC) assay with ultraviolent detection was used to detect the concentration of 8 conjugated bile acids (glycocholic acid, GCA; taurocholic acid, TCA; glycochenodeoxycholic acid, GCDCA; taurochenodeoxycholic acid, TCDCA; glycodeoxycholic acid, GDCA; taurodeoxycholic acid, TDCA; taurolithocholic acid, TLCA; tauroursodeoxycholic acid, TUDCA) in bile samples and serum samples. The diagnostic efficacy of serum GCA, GCDCA and TCDCA was evaluated. Results These 8 conjugated bile acids in gallbladder bile and serum were completely identified within 10 minutes with good linearity (correlation coefficient: R>0.9900; linearity range: 3.91-500 µg/mL). Among these conjugated bile acids, the levels of gallbladder bile GCDCA and TCDCA in the CP group were significantly higher than those in the AP group (p<0.05). Furthermore, serum GCDCA and TCDCA as well as GCA were significantly higher in the AP group than the CP group (p<0.05). Serum GCDCA alone (≤12 µg/mL) had relatively better diagnostic efficacy than the other conjugated bile acids. Conclusions The levels of serum GCA, GCDCA and TCDCA may be valuable for differentiation of APs and CPs.

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