Impact of ginsenoside Rb1 on gut microbiome and associated changes in pharmacokinetics in rats

Ginsenoside Rb₁ exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb₁. However, the impact of gut microbiota on the pharmacokinetics of Rb₁ are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb₁ intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb₁ and Rd were substantially affected after orally supplementing Rb₁ (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb₁ and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb₁ administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb₁ pharmacokinetics.