scholarly journals Colesevelam Reduces Ethanol-Induced Liver Steatosis in Humanized Gnotobiotic Mice

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1496
Author(s):  
Noemí Cabré ◽  
Yi Duan ◽  
Cristina Llorente ◽  
Mary Conrad ◽  
Patrick Stern ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Liver Steatosis ◽  
Elevated Serum ◽  
Bile Acid Metabolism ◽  
Functional Changes ◽  
Serum Bile Acids ◽  
Gnotobiotic Mice ◽  
Related Liver Disease

Alcohol-related liver disease is associated with intestinal dysbiosis. Functional changes in the microbiota affect bile acid metabolism and result in elevated serum bile acids in patients with alcohol-related liver disease. The aim of this study was to identify the potential role of the bile acid sequestrant colesevelam in a humanized mouse model of ethanol-induced liver disease. We colonized germ-free (GF) C57BL/6 mice with feces from patients with alcoholic hepatitis and subjected humanized mice to the chronic–binge ethanol feeding model. Ethanol-fed gnotobiotic mice treated with colesevelam showed reduced hepatic levels of triglycerides and cholesterol, but liver injury and inflammation were not decreased as compared with non-treated mice. Colesevelam reduced hepatic cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1) protein expression, although serum bile acids were not lowered. In conclusion, our findings indicate that colesevelam treatment mitigates ethanol-induced liver steatosis in mice.

scholarly journals Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12431
Author(s):  
Russell R. Fling ◽  
Timothy R. Zacharewski
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Dose Dependent ◽  
Alcoholic Fatty Liver Disease

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.

Serum Bile Acids in Patients with Liver Disease

1965 ◽  
Vol 11 (5) ◽  
pp. 547-553 ◽  
Author(s):  
Samuel J Levin ◽  
Morton K Schwartz
Keyword(s):  
Alkaline Phosphatase ◽  
Liver Disease ◽  
Bile Acid ◽  
Liver Metastases ◽  
Viral Hepatitis ◽  
Bile Acids ◽  
Liver Diseases ◽  
Serum Bile Acids ◽  
Yield Information

Abstract By means of a sensitive fluorometric technic, serum bile acids were determined in patients with various liver diseases. Correlations were shown between the bile acid values and those of transaminase and alkaline phosphatase in cases of liver metastases, and bile acid and transaminase values in cases of viral hepatitis. For most clinical purposes, however, the determination does not yield information which cannot be obtained more readily using currently accepted methods.

scholarly journals Bile Acid Signaling: Mechanism for Bariatric Surgery, Cure for NASH?

2015 ◽  
Vol 33 (3) ◽  
pp. 440-446 ◽  
Author(s):  
Rohit Kohli ◽  
Andriy Myronovych ◽  
Brandon K. Tan ◽  
Rosa-Maria Salazar-Gonzalez ◽  
Lili Miles ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Adjustable Gastric Band ◽  
Metabolic Effects ◽  
Signaling Mechanism ◽  
Serum Bile Acids ◽  
Long Run

Bariatric surgery is the most effective and durable treatment option for obesity today. More importantly, beyond weight loss, bariatric procedures have many advantageous metabolic effects including reversal of obesity-related liver disease - nonalcoholic steatohepatitis (NASH). NASH is an important comorbidity of obesity given that it is a precursor to the development of liver cirrhosis that may necessitate liver transplantation in the long run. Simultaneously, we and others have observed increased serum bile acids in humans and animals that undergo bariatric surgery. Specifically, our preclinical studies have included experimental procedures such as ‘ileal transposition' or bile diversion and established procedures such as Roux-en-Y gastric bypass and the adjustable gastric band. Importantly, these effects are not simply the result of weight loss since our data show that the resolution of NASH and increase in serum bile acids are not seen in rodents that lose an equivalent amount of weight via food restriction. In particular, we have studied the role of altered bile acid signaling, in the potent impact of a bariatric procedure termed ‘vertical sleeve gastrectomy' (VSG). In this review we focus on the mechanisms of NASH resolution and weight loss after VSG surgery. We highlight the fact that bariatric surgeries can be used as ‘laboratories' to dissect the mechanisms by which these procedures work to improve obesity and fatty liver disease. We describe key bile acid signaling elements that may provide potential therapeutic targets for ‘bariatric-mimetic technologies' that could produce benefits similar to bariatric surgery - but without the surgery!

scholarly journals Serum Bile Acids in Cholestatic Liver Disease: Their Measurement and Significance

1972 ◽  
Vol 9 (1-6) ◽  
pp. 67-73 ◽  
Author(s):  
G. M. Murphy
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Specific Method ◽  
Cholestatic Liver Disease ◽  
Serum Bile Acids

A relatively rapid and specific method for the estimation of serum individual bile acids, conjugated and free, in small volumes (1 ml) of sera from patients with liver disease has been developed. This method has been applied to a study of 25 patients with liver disease. Cholestatic liver disease has been found to be associated with an increase in serum monohydroxy bile acids which appear to be of an unsaturated nature. No association was found between the concentration of any particular bile acid and the presence or absence of pruritus.

scholarly journals Non-Alcoholic Fatty Liver Disease, Bile Acids and Intestinal Microbiota

2018 ◽  
Vol 28 (4) ◽  
pp. 84-90
Author(s):  
R. V. Maslennikov ◽  
Yu. V. Evsyutina
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Intestinal Microbiota ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Aim.  The aim of the review is to present current data on the relationship between non-alcoholic fatty liver disease (NAFLD) with the metabolic disorders of bile acids (BA) and changes in the composition of the intestinal microbiota.Background.  NAFLD is accompanied by a change in the intestinal microbiotic composition: the proportion of taxa deconjugating BAs increases, while the proportion of taxa converting primary BAs to secondary ones decreases. The number of bacteria forming lipopolysaccharide (LPS) also increases. LPS, entering the liver with the portal vein blood, promotes the development of its inflammation and insulin resistance. The disturbance of bile acid metabolism through the effect on the FXR and TGR5 receptors also leads to insulin resistance and liver steatosis. FXR probiotics and agonists are promising drugs for the NAFLD treatment.Conclusion.  In the course of NAFLD, a change in the composition of the intestinal microbiota is observed, which contributes to the development of inflammation in the liver and disrupts the metabolism of bile acids, leading to insulin resistance. 

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