scholarly journals Gut Microbiota and Host Cyp450s Co-contribute to Pharmacokinetic Variability in Mice with Non-Alcoholic Steatohepatitis: Effects Vary From Drug to Drug

2021 ◽  
Author(s):  
Jing Guo ◽  
Ying Xu ◽  
Li-jie Chen ◽  
Song-xia Zhang ◽  
Yu-ligh Liou ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Pharmacokinetic Variability ◽  
Alcoholic Steatohepatitis

Gut Microbiota and Host Cyp450s Co-contribute to Pharmacokinetic Variability in Mice With Non-Alcoholic Steatohepatitis: Vary From Drug to Drug

2021 ◽  
Author(s):  
Jing Guo ◽  
Ying Xu ◽  
Li-Jie Chen ◽  
Song-xia Zhang ◽  
Tai Rao ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Gut Microbiota ◽  
Intravenous Administration ◽  
Underlying Mechanism ◽  
Control Group ◽  
Intragastric Administration ◽  
Minimal Effect ◽  
Pharmacokinetic Variability ◽  
Alcoholic Steatohepatitis ◽  
Nash Group

Abstract Background: Pharmacokinetic variability in disease state is common in clinical practice, but the underlying mechanism remains unclear. We aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH).Methods: The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administration of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol compared with the control group. The pharmacokinetic variability of the drugs and its relation with changes of gut microbiota and host Cyp450s were compared and analyzed.Results: The exposure of all drugs, except metoprolol, significantly increased in the NASH group under intragastric administration. However, no significant increase in the exposure of all drugs, except tolbutamide, was observed in the NASH group under intravenous administration. The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity of the gut microbiota. By contrast, the pharmacokinetic variability of tolbutamide was mainly related to the change in host Cyp2c65. However, gut microbiota and host Cyp450s exerted minimal effect on the pharmacokinetic variability of metoprolol.Conclusions: Gut microbiota and host Cyp450s co-contribute the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug.

scholarly journals Effects of Dietary Intervention on Gut Microbiota and Metabolic-Nutritional Profile of Outpatients with Non-Alcoholic Steatohepatitis: a Randomized Clinical Trial

2019 ◽  
Vol 28 (3) ◽  
pp. 279-287 ◽  
Author(s):  
Fabiana De Faria Ghetti ◽  
Daiane Gonçalves De Oliveira ◽  
Juliano Machado De Oliveira ◽  
Lincoln Eduardo Villela Vieira de Castro Ferreira ◽  
Dionéia Evangelista Cesar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gut Microbiota ◽  
Randomized Clinical Trial ◽  
Bacterial Overgrowth ◽  
Diet Group ◽  
Control Group ◽  
Model Assessment ◽  
Nutritional Profile ◽  
Alcoholic Steatohepatitis ◽  
The Impact

Background & Aims: Modulation of the gut microbiota emerges as a therapeutic possibility to improve health. Our objective was to compare the impact of three months of intervention with diet plus nutritional orientation versus only nutritional orientation on the gut microbiota and metabolic-nutritional profile of outpatients with non-alcoholic steatohepatitis. Methods: It was a randomized clinical trial with 40 outpatients (49.48 ± 10.3 years), allocated in two groups: DIET group (n=20), who received diet (1.651.34 ± 263.25 kcal; 47% carbohydrates, 28% lipids, 25% proteins, 30 g fibers) and nutritional orientation, and control group (n = 20), which received only nutritional orientation. Results: The DIET group, in relation to baseline, presented a reduction in body weight (p<0.001), BMI (p<0.001), waist circumference (p=0.001), percentage of fat (p=0.002), serum aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p=0.001), glycemia (p=0.003), homeostasis model assessment of insulin resistance (p=0.017), total cholesterol (p=0.014), and triacylglycerols (p=0.008), whereas the control group did not present changes. After intervention, the small intestinal bacterial overgrowth frequency was 30% in the DIET group and 45% in the control group (p=0.327). In the DIET group, an increase in the density of total microorganisms (3.76 ± 7.17 x 10 8 cells g -1 ; p=0.048) was detected, while in the control group reduced Bacteroidetes (-0.77 ± 2.01 x 10 8 cells g -1 , p=0.044) and Verrucomicrobiales (-0.46 ± 0.75 x 10 8 cells g -1 ; p=0.022) were observed. Conclusions: The results suggest that exclusively dietary modifications contribute to health promotion in non-alcoholic steatohepatitis and should be the basis of nutritional treatment for this condition.

Effects of surface-deacetylated chitin nanofibers on non-alcoholic steatohepatitis model rats and their gut microbiota

2020 ◽  
Vol 164 ◽  
pp. 659-666 ◽  
Author(s):  
Miwa Goto ◽  
Daisuke Iohara ◽  
Akihiro Michihara ◽  
Shinsuke Ifuku ◽  
Kazuo Azuma ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Alcoholic Steatohepatitis ◽  
Chitin Nanofibers

scholarly journals Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review

2020 ◽  
Vol 21 (17) ◽  
pp. 5999
Author(s):  
Yi-Hsun Chen ◽  
Wei-Kai Wu ◽  
Ming-Shiang Wu
Keyword(s):  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Therapeutic Strategies ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Gut Barrier Function ◽  
And Function ◽  
Alcoholic Fatty Liver Disease ◽  
Gut Microbiota Composition

Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.

Sign in / Sign up

Export Citation Format

Share Document