Medicinal Plant Research 2025, Vol.15, No.4, 169-177 http://hortherbpublisher.com/index.php/mpr 172 4 Influence of Gut Microbiota on the Pharmacodynamics of Ginseng 4.1 Gut microbiota involvement in immunomodulatory effects Ginseng and its polysaccharides modulate the immune function by adjusting gut microbiota balance, stimulating beneficial flora such as Bifidobacterium and Lactobacillus, and restoring immune homeostasis. These changes induce anti-inflammatory cytokine and immunoglobulin production and the improvement of gut barrier function, thereby improving systemic immune regulation (Li et al., 2019; Wang et al., 2021; Zhou et al., 2025). 4.2 Microbiota-mediated regulation of anti-inflammatory and antioxidant activities Gut microbiota hydrolyzes ginsenosides into compounds that have improved anti-inflammatory and antioxidant activities. They suppress inflammatory signaling, restrict oxidative stress, and modulate cytokine secretion. Ginseng polysaccharides also correct autophagic activity and inhibit NF-κB signaling and thereby mediate intestinal and systemic anti-inflammatory effect (Kim, 2017; Ren et al., 2022). 4.3 Gut–brain axis mechanisms in neuroprotection and cognitive improvement Ginseng interacts with the gut–brain axis through remodeling the gut microbiota, increasing the relative abundance of beneficial taxa, and changing microbial metabolites such as short-chain fatty acids and tryptophan derivatives. This change suppresses neuroinflammation, enhances antioxidant defense in brain tissue, and improves cognitive function and neuroprotection, as reported in aging and stress models (Iqbal et al., 2024; Lin et al., 2024). 4.4 Antitumor effects and synergistic roles of microbial metabolites Gut microbiota-catalyzed conversion of ginsenosides yields metabolites such as compound K, which possess strong antitumor activity. Ginseng polysaccharides may also enhance the antitumor effects of immunotherapies (e.g., anti-PD-1) by regulating microbial metabolites and suppressing immunosuppressive factors, resulting in increased tumor inhibition and therapeutic efficacy (Kim, 2017; Huang et al., 2021; Zhou et al., 2021). 5 Applications of Multi-Omics and Systems Biology Approaches 5.1 Metabolomics for analyzing ginseng metabolites and microbiota-derived co-metabolites Metabolomics provides the capability of detecting and quantifying metabolites of ginsenoside and co-metabolites produced by microbiota in biological samples. For example, through carrying out microbiome-metabolomics analysis, co-administration of ginseng polysaccharides and ginsenosides was found to restore gut microbiota balance and alter fecal metabolites associated with immunometabolism and gut-barrier integrity, including uric acid, xanthurenic acid, and numerous lysophospholipids. These results emphasize the utility of metabolomics in connecting particular metabolic alterations to therapeutic responses and gut microbial modulation (Liang et al., 2021; Zhou et al., 2021). 5.2 Metagenomics and transcriptomics for revealing functional genes and pathways of gut microbiota Metagenomics and metatranscriptomics provide global views of gut microbiota gene functional expression and taxonomic structure. These approaches have been used to identify dominant bacterial phyla and functional pathways of ginsenoside transformation, immunomodulatory activities, and metabolic well-being. For instance, 16S rRNA sequencing and metagenomics have proven that ginseng treatment increases beneficial bacteria and functional genes that are in charge of the production of short-chain fatty acids and immune modulation (Daliri et al., 2021; Huang et al., 2021; Duan et al., 2025). 5.3 Network pharmacology of microbe–drug interactions Network pharmacology integrates multi-omics information to reconstruct complex interactions between ginseng compounds, gut microbiota metabolites, and host targets. This approach rationalizes ginseng and gut microbiota synergistic efficacy, predicts therapeutic efficacy, and discovers biomarkers for precision medicine. Systems biology models and network analyses have been proposed to disclose multi-layer interactions and guide precision medicine approaches in ginseng research (Daliri et al., 2021; Chen et al., 2022; Chetty and Blekhman, 2024).
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