1. Lactobacillus rhamnosus GG ameliorates triptolide-induced liver injury through modulation of the bile acid-FXR axis.
- Author
-
Hu S, Tang B, Lu C, Wang S, Wu L, Lei Y, Tang L, Zhu H, Wang D, and Yang S
- Subjects
- Animals, Male, Mice, Liver drug effects, Liver metabolism, Liver pathology, Probiotics therapeutic use, Probiotics pharmacology, Fecal Microbiota Transplantation, Inflammasomes metabolism, Signal Transduction drug effects, Diterpenes pharmacology, Phenanthrenes pharmacology, Chemical and Drug Induced Liver Injury metabolism, Chemical and Drug Induced Liver Injury prevention & control, Lacticaseibacillus rhamnosus, Gastrointestinal Microbiome drug effects, Epoxy Compounds pharmacology, Bile Acids and Salts metabolism, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Receptors, Cytoplasmic and Nuclear metabolism
- Abstract
Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF