Prebiotics enhance the systemic exposure of ginsenosides in rats by modulating the gut microbiota

Gut microbiota plays a crucial role in the biotransformation of ginsenosides to their major bioactive metabolite ginsenoside compound K (CK). Prebiotic fiber treatment targeting gut microbiota potentially enhance the formation and consequent absorption of ginsenoside CK. Herein, we investigated the effect of three commercial prebiotic fibers [fructooligosaccharide (FOS), galactooligosaccharide (GOS) and fibersol-2] on the pharmacokinetics of ginsenoside Rb1, gut microbiota compositions/metabolic functions and their potential underlying mechanisms.Methods: A total of 32 male Sprague-Dawley rats were oral administered of Rb1 after 2 weeks intervention with FOS, GOS and fibersol-2, respectively. Pharmacokinetics analysis of ginsenoside Rb1 and its metabolites were performed, while gut microbiota was taxonomically and functionally analyzed using total 16S rDNA microbiota and metagenome shotgun sequencing.Results: The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0-t) of ginsenoside Rb1 and its intermediate metabolite ginsenoside Rd, F2 and CK of the three prebiotics intervention groups were significantly increased than the control. The overall gut microbiota responded to the prebiotics intervention showed significant differences both at the taxonomical and functional level. Most notably, the genera Prevotella, which possesses the potential function to hydrolyze ginsenoside Rb1 to CK, were significantly elevated in prebiotics groups (P<0.05). The gut metagenome results indicated that the functional enrichment of genes occurs for functions such as terpenoids and polyketides metabolism, glycolysis/gluconeogenesis, propanoate metabolism and the citrate cycle in prebiotics intervention groups.Conclusion: These results indicated that prebiotics may promote the metabolic conversion of ginsenosides Rb1 to CK and the subsequent absorption of CK in the gastrointestinal tract by strengthening the ginsenosides hydrolytic activity of gut microbiota.