1. Lactobacillus rhamnosus GG ameliorates triptolide-induced liver injury through modulation of the bile acid-FXR axis.
- Author
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Hu, Shiping, Tang, Bo, Lu, Cheng, Wang, Sumin, Wu, Lingyi, Lei, Yuanyuan, Tang, Li, Zhu, Hongbin, Wang, Dongxu, and Yang, Shiming
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LACTOBACILLUS rhamnosus , *GUT microbiome , *FECAL microbiota transplantation , *LIVER injuries , *FARNESOID X receptor , *BILE salts - 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. [Display omitted] • Gut microbiota is involved in TP-induced liver injury. • LGG supplementation could ameliorates TP hepatotoxicity. • LGG-mediated BA metabolism plays a vital role in TP hepatotoxicity. • The protective role of LGG in TP hepatotoxicity by regulating the BA-FXR Axis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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