Prebiotics enhance the biotransformation and bioavailability of ginsenosides in rats by modulating gut microbiota

J Ginseng Res. 2021 Mar;45(2):334-343. doi: 10.1016/j.jgr.2020.08.001. Epub 2020 Aug 7.

Abstract

Background: Gut microbiota mainly function in the biotransformation of primary ginsenosides into bioactive metabolites. Herein, we investigated the effects of three prebiotic fibers by targeting gut microbiota on the metabolism of ginsenoside Rb1 in vivo.

Methods: Sprague Dawley rats were administered with ginsenoside Rb1 after a two-week prebiotic intervention of fructooligosaccharide, galactooligosaccharide, and fibersol-2, respectively. Pharmacokinetic analysis of ginsenoside Rb1 and its metabolites was performed, whilst the microbial composition and metabolic function of gut microbiota were examined by 16S rRNA gene amplicon and metagenomic shotgun sequencing.

Results: The results showed that peak plasma concentration and area under concentration time curve of ginsenoside Rb1 and its intermediate metabolites, ginsenoside Rd, F2, and compound K (CK), in the prebiotic intervention groups were increased at various degrees compared with those in the control group. Gut microbiota dramatically responded to the prebiotic treatment at both taxonomical and functional levels. The abundance of Prevotella, which possesses potential function to hydrolyze ginsenoside Rb1 into CK, was significantly elevated in the three prebiotic groups (P < 0.05). The gut metagenomic analysis also revealed the functional gene enrichment for terpenoid/polyketide metabolism, glycolysis, gluconeogenesis, propanoate metabolism, etc.

Conclusion: These findings imply that prebiotics may selectively promote the proliferation of certain bacterial stains with glycoside hydrolysis capacity, thereby, subsequently improving the biotransformation and bioavailability of primary ginsenosides in vivo.

Keywords: ANOVA, analysis of variance; AUC, area under the concentration-time curve; Bioavailability; Biotransformation; CAT, CAZymes Analysis Toolkit; CAZymes, carbohydrate active enzymes; CK, compound K; Cmax, peak plasma concentration; FDR, false discovery rate; FOS, fructooligosaccharide; GOS, galactooligosaccharide; Ginsenoside; Gut microbiota; IS, internal standard; KEGG, the Kyoto Encyclopaedia of Genes and Genomes; LCA, lowest common ancestor; LDA, linear discriminant analysis; LEfSe, LDA effect size; LLOQs, lower limits of quantifications; MANOVA, multivariate ANOVA; MRM, multiple reaction monitoring; NMDS, non-metric multidimensional scaling; PCA, principal component analysis; PCoA, principal coordinates analysis; Prebiotic; SD, Sprague Dawley; SRA, Sequence Read Archive; Tmax, time of maximum plasma concentration; UPLC-ESI-QqQ-MS/MS, ultra-high pressure liquid chromatography coupled to an electrospray ionization source and a triple-quadrupole mass spectrometer.