Analysis of bile acids in conventional and germfree rats

Madsen, David C.; Beaver, Margaret H.; Liu, Chang; Bruckner-Kardoss, Edith; Wostmann, Bernard S.

doi:10.1016/s0022-2275(20)36993-5

Cited by 80 publications

(9 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the same washout time period (e.g., 8-12 h), TDC, T--MC, and TUDC became undetectable in fistula biles. Our results verified that TC, T-␤-MC, and TCDC are primary BS, and TDC, T--MC, and TUDC are secondary BS in mice (41).…”

Section: Circulating Bs Pool Sizessupporting

confidence: 79%

See 1 more Smart Citation

Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: pathophysiology of biliary lipid secretion

Wang

Lammert

Paigen

et al. 1999

Journal of Lipid Research

105

View full text Add to dashboard Cite

The inbred C57L strain but not the AKR strain of mice carry Lith genes that determine cholesterol gallstone susceptibility. When C57L mice are fed a lithogenic diet containing 15% fat, 1% cholesterol, and 0.5% cholic acid, gallbladder bile displays rapid cholesterol supersaturation, mucin gel accumulation, increases in hydrophobic bile salts, and rapid phase separation of solid and liquid crystals, all of which contribute to the high cholesterol gallstone prevalence rates ( D. Q-H. Wang, B. Paigen, and M. C. Carey. J. Lipid Res. 1997. 38: 1395-1411). We have now determined the hepatic secretion rates of biliary lipids in fasting male and female C57L and AKR mice and the intercross (C57L ؋ AKR)F 1 before and at frequent intervals during feeding the lithogenic diet for 56 days. Bile flow and biliary lipid secretion rates were measured in the first hour of an acute bile fistula and circulating bile salt pool sizes were determined by the "washout" technique after cholecystectomy. Compared with AKR mice, we found that i ) C57L and F 1 mice on chow displayed significantly higher secretion rates of all biliary lipids, and larger bile salt pool sizes, as well as higher bile salt-dependent and bile salt-independent flow rates; ii ) the lithogenic diet further increased biliary cholesterol and lecithin outputs, but bile salt outputs remained constant. Biliary coupling of cholesterol to lecithin increased approximately 30%, setting the biophysical conditions necessary for cholesterol phase separation in the gallbladder; and iii ) no gender differences in lipid secretion rates were noted but male mice exhibited significantly more hydrophobic bile salt pools than females. We conclude that in gallstone-susceptible mice, Lith genes determine increased outputs of all biliary lipids but promote cholesterol hypersecretion disproportionately to lecithin and bile salt outputs thereby inducing lithogenic bile formation. -Wang, D. Q-H., F. Lammert, B. Paigen, and M. C. Carey. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: pathophysiology of biliary lipid secretion.

show abstract

Section: Circulating Bs Pool Sizessupporting

confidence: 79%

“…5, bottom panel). This verifies that T-␤-MC, TC, and TCDC are primary BS, and TUDC, TDC, and T--MC are secondary BS as observed in conventional compared with germ-free rodents (41).…”

Section: Pathophysiological Characterization Of Hepatic Bilessupporting

confidence: 74%

Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: pathophysiology of biliary lipid secretion

Wang

Lammert

Paigen

et al. 1999

Journal of Lipid Research

105

View full text Add to dashboard Cite

show abstract

“…Consequently, every intervention increasing the bile acid pool size or hydrophobicity of pool composition (eg, cholic acid feeding) will cause aggravation and every intervention reducing bile acid pool size (eg, Asbt inhibitors, FGF19, bile acid binding resins) will ameliorate cholangitis and consequently liver fibrosis. Importantly, it has been known since the 1970s that GF conditions but also antibiotics increase the bile acid pool size in rodents 9. In this respect, the current findings of Awoniyi et al 6 are therefore in line with previous observations,10 but the rescue of the liver phenotype with Lachnospiraceae and purified SCFAs is new and fascinating!…”

supporting

confidence: 86%

Bacteria as key players in primary sclerosing cholangitis?

Fickert

2022

Gut

View full text Add to dashboard Cite

“…It has been reported that administration of lithocholic acid (LCA) to GF mice increased Cyp3a11 mRNA expression level in the liver, and ciprofloxacin administration decreased Cyp3a11 mRNA expression level and LCA exposure in the liver . LCA is a secondary bile acid produced by intestinal bacteria, and is an activator of pregnane X receptor (PXR) and farnesoid X receptor (FXR), which are involved in positive regulation of Cyp3A4/3a11 expression. − It has been reported that CYP2B6, CYP2C9, Ces2a, and Ces2c expressions are regulated positively by PXR, and BSEP is regulated positively by FXR. − However, Cyp51a1, which is involved in the cholesterol biosynthetic pathway as a sterol 14α-demethylase, is regulated negatively by FXR. , Therefore, suppression of Cyp3a11, Cyp2b10, Cyp2c29, Ces2a, Ces2c, and Bsep and induction of Cyp51a1 may result from the reduction of LCA due to dysbiosis (Figure A and B).…”

Section: Discussionmentioning

confidence: 99%

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

Effect of Intestinal Flora on Protein Expression of Drug-Metabolizing Enzymes and Transporters in the Liver and Kidney of Germ-Free and Antibiotics-Treated Mice

et al. 2016

View full text Add to dashboard Cite

Dysbiosis (alteration of intestinal flora) is associated with various host physiologies, including diseases. The purpose of this study was to clarify the effect of dysbiosis on protein expression levels in mouse liver and kidney by quantitative proteomic analysis, focusing in particular on drug-metabolizing enzymes and transporters in order to investigate the potential impact of dysbiosis on drug pharmacokinetics. Germ-free (GF) mice and antibiotics-treated mice were used as dysbiosis models. Expression levels of 825 and 357 proteins were significantly changed in the liver and kidney, respectively, of GF mice (vs specific-pathogen-free mice), while 306 and 178 proteins, respectively, were changed in antibiotics-treated mice (vs vehicle controls). Among them, 52 and 16 drug-metabolizing enzyme and transporter proteins were significantly changed in the liver and kidney, respectively, of GF mice, while 25 and 8, respectively were changed in antibiotics-treated mice. Expression of mitochondrial proteins was also changed in the liver and kidney of both model mice. In GF mice, Oatp1a1 was decreased in both the liver and kidney, while Sult1a1 and two Cyp enzymes were increased and Gstp1, four Cyp enzymes, three Ces enzymes, Bcrp1, and Oct1 were decreased in the liver. In antibiotics-treated mice, Cyp51a1 was increased and three Cyp enzymes, Bcrp1, and Bsep were decreased in the liver. Notably, the expression of Cyp2b10 and Cyp3a11 was greatly decreased in the liver of both models. Cyp2b activity in the liver microsomal fraction was also decreased. Our results indicate that dysbiosis changes the protein expression of multiple drug-metabolizing enzymes and transporters in the liver and kidney and may alter pharmacokinetics in the host.

show abstract

Analysis of bile acids in conventional and germfree rats

Cited by 80 publications

References 7 publications

Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: pathophysiology of biliary lipid secretion

Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: pathophysiology of biliary lipid secretion

Bacteria as key players in primary sclerosing cholangitis?

Effect of Intestinal Flora on Protein Expression of Drug-Metabolizing Enzymes and Transporters in the Liver and Kidney of Germ-Free and Antibiotics-Treated Mice

Contact Info

Product

Resources

About