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Objective To investigate the diversity and composition of gut microbiota in patient with cholestatic liver disease, and explore their correlation with clinical parameters. Methods Fresh stool samples from 16 patients with cholestatic liver disease and 19 healthy controls were collected, and 16S rRNA sequencing was used to analyze the diversity of gut microbiota and composition characteristics. Pearson analysis was employed to analyze the correlation between the different bacteria and clinical parameters. Results There were no statistical differences in the baseline data, such as sex, age and body mass index (BMI) in study subjects (P>0.05), but significant differences were observed in serum indexes among them (P < 0.01). The results of α diversity showed that Chao1 and Shannon indexes were lower in the study group, but there was no statistical difference (P>0.05). β diversity results indicated that the species diversity had significant difference between 2 group (P < 0.01). Further analysis of microbiota composition showed largely relative abundance of Bacteroides, Lachnoclostridium, Veillonella, Roseburia and Escherichia shigella (P < 0.05), while the abundance of Blautia were dramatically decreased (P < 0.05). Pearson analysis displayed that Lachnoclostridium was strongly correlated with serum level of alkaline phosphatase (ALP) (P < 0.01) and gamma-glutamyl transferase (GGT) (P < 0.05), and Veillonella was also strongly correlated with GGT (P < 0.05). Conclusion Compared with healthy controls, the patients with cholestatic liver disease have obvious characteristic changes in the gut microbiota. The relatively high abundance of Veillonella is closely assocatied with cholestatic liver disease.

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]