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.

scholarly journals Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1358 ◽  
Author(s):  
Aline Gottlieb ◽  
Ali Canbay
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
The Body ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Primary Biliary Cholangitis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a complex disease, affecting not just the liver, but also all other organs in the body. Despite an increasing amount of people worldwide developing NAFLD and having it progress to non-alcoholic steatohepatitis (NASH) and potentially cirrhosis, there is still no approved therapy. Therefore, huge efforts are being made to find and develop a successful treatment. One of the special interests is understanding the liver–gut axis and especially the role of bile acids in the progression of NAFLD. Farnesoid X receptor (FXR)-agonists have been approved und used in other liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), and have shown signs of being able to decrease inflammation and potentially steatosis. This review will mainly focus on targets/ligands that play an important role in bile acid metabolism and give an overview of ongoing clinical as well as pre-clinical trials. With the complexity of the issue, we did not aim at giving a complete review, rather highlighting important targets and potential treatments that could be approved for NAFLD/NASH treatment within the next few years.

A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease

2010 ◽  
Vol 120 (7) ◽  
pp. 287-296 ◽  
Author(s):  
Rika Iwata ◽  
Katharina Baur ◽  
Bruno Stieger ◽  
Joachim C. Mertens ◽  
Ann K. Daly ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Hepatitis C ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Chronic Hcv ◽  
Alcoholic Fatty Liver Disease

Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member II) 1331T>C and NR1H4 (nuclear receptor) −1G>T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol >40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012–1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1–110) μmol/l compared with 3.5 (1–61) μmol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P=0.047) was observed in the χ2 test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F≥2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.

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. 

scholarly journals A look at new therapeutic opportunities in patients with non-alcoholic fatty liver disease

2019 ◽  
Vol 16 (3) ◽  
pp. 37-45
Author(s):  
Ekaterina E. Mishina ◽  
Alexander Y. Mayorov ◽  
Apollinariya V. Bogolyubova ◽  
Pavel O. Bogomolov ◽  
Maria V. Matsievich ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Processes ◽  
Active Research ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is considered to be the liver manifestation of metabolic syndrome. Currently, there is no etiotropic treatment of NAFLD, so an active research for new methods of treatment is underway. In the meantime, drugs are used to treat comorbid conditions, such as dyslipidemia, arterial hypertension, obesity, type 2 diabetes, which are present in varying degrees in patients. This review considers medications that are used in patients with NAFLD and related concomitant features, and also describes new strategies for regressing changes in liver tissue in NAFLD. In our opinion, one of the promising groups of drugs are agonists of the farnesoid X receptor (FXR). FXR belongs to the group of nuclear receptors, which are ligand-activated transcription factors that regulate the genes involved in metabolism. FXR agonists can claim to be a new promising drug for the treatment of NAFLD and related diseases influencing carbohydrate metabolism, fat metabolism, bile acid metabolism, as well as inflammatory processes in the liver to ensure metabolic homeostasis.

scholarly journals Bile Acid and Fibroblast Growth Factor 19 Regulation in Obese Diabetics, and Non-Alcoholic Fatty Liver Disease after Sleeve Gastrectomy

2019 ◽  
Vol 8 (6) ◽  
pp. 815 ◽  
Author(s):  
Hsien-Hao Huang ◽  
Wei-Jei Lee ◽  
Shu-Chun Chen ◽  
Tung-Fang Chen ◽  
Shou-Dong Lee ◽  
...  
Keyword(s):  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Total Bile Acid ◽  
Alcoholic Fatty Liver ◽  
Liver Index ◽  
Fatty Liver Index ◽  
Total Bile Acids ◽  
Alcoholic Fatty Liver Disease

Background: Sleeve gastrectomy (SG) is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD); however, the mechanism is not completely understood. Bile acids and fibroblast growth factors (FGFs) are involved in the regulation of energy metabolism. Methods: We investigated the roles of total bile acid and FGF 19 in T2DM remission and NAFLD improvement in obese subjects undergoing SG. A total of 18 patients with obesity and T2DM undergoing laparoscopic SG were enrolled in this study. Serial plasma total bile acid and FGF 19 levels were measured, while the fatty liver index was calculated before and after surgery. Results: The FGF 19 level significantly increased, and the total bile acid level and fatty liver index decreased 1 year after surgery. The complete T2DM remission rate was 66.7% one year after surgery; the complete remitters had significantly lower FGF 19 levels and higher insulin levels than the non-complete remitters. The complete remitters also had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. The fatty improvers had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. Conclusion: The total bile acids level and fatty liver index decreased, and the FGF 19 levels increased 1 year after SG. Both T2DM complete remitters and NAFLD improvers showed significantly decreased total bile acid levels and increased FGF 19 levels 1 year after SG. Plasma total bile acids and FGF 19 might have roles in T2DM remission and NAFLD improvement. Low preoperative FGF 19 levels might be a predictor for NAFLD improvement after SG.

scholarly journals Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0151829 ◽  
Author(s):  
Marialena Mouzaki ◽  
Alice Y. Wang ◽  
Robert Bandsma ◽  
Elena M. Comelli ◽  
Bianca M. Arendt ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease
Sign in / Sign up

Export Citation Format

Share Document