Medicinal Plant Research 2025, Vol.15, No.4, 169-177 http://hortherbpublisher.com/index.php/mpr 173 6 Individual Differences and Clinical Significance of Ginseng–Microbiota Interactions 6.1 Gut microbiota differences as explanations for variations in ginseng efficacy Gut microbiota population and diversity are greatly varied among individuals due to variations in genetics, diet, environment, and drug usage. Such variations cause great diversity in gut microbiota metabolic activity, particularly in biotransformation of ginsenoside into their more bioactive metabolites. Therefore, various gut microbial communities in individuals will have different pharmacological effects and therapeutic outcomes from ginseng supplementation (Zhao et al., 2023; Zhang, 2024). For example, some bacteria, including Bifidobacterium, have been reported to be responsible for higher ginsenoside conversion, thus enhancing the bioavailability and efficacy of ginseng (Dong et al., 2017; Seong et al., 2021). 6.2 Implications for population stratification and personalized medicine Population stratification based on gut microbiota types can preclude the effect of ginseng and improve treatment strategies. Clinical evidence has shown that the efficacy of ginseng, for instance, in the modulation of metabolic syndrome, relies on the initial composition of the gut microbiota and enterotype. This makes it possible to apply gut microbiota analysis as a marker of ginseng efficacy prediction and tailored treatment strategies (Dong et al., 2017). Stratified medicine strategies that consider variation in gut microbiota potentially can improve clinical efficacy and reduce response heterogeneity to ginseng. 6.3 Application of gut microbiota interventions to optimize ginseng efficacy Interventions targeting the gut microbiota, such as administration of probiotic, prebiotic, or fermented ginseng products, can modulate the gut environment in favor of beneficial bacteria involved in ginsenoside metabolism. These strategies were shown to enhance ginseng's pharmacological effects, restore gut microbial homeostasis, and improve disease status in animal models and clinics (Li et al., 2019; Chen et al., 2022; Peng et al., 2022). Probiotic fermentation technology and dietary supplementation of ginseng fiber are promising strategies to increase the production of bioactive ginseng metabolites and optimize therapeutic efficacy (Kim, 2017; Qu et al., 2020; Song et al., 2023) (Figure 2). 7 Clinical Applications and Translational Prospects 7.1 Interactions between ginseng preparations and gut microbiota Preparations of ginseng, i.e., fermented and polysaccharide-constituents-enriched preparations, also interact dynamically with the gut microbiota. The interactions enhance the bioactivation of ginsenosides to more active metabolites, increase richness in beneficial bacteria (e.g., Bifidobacterium, Bacteroides, and Akkermansia), and decrease pathogenic taxa. This regulation enhances metabolic, inflammatory, and neurological disease outcomes. Fermented ginseng foods, particularly, demonstrated improved activity in lipid metabolism regulation and gut microbe recovery in clinical trials and animal models (Seong et al., 2021; Iqbal et al., 2024; Zhou et al., 2025). 7.2 Development of combination therapies with microbiota modulators Synergistic interaction with microbiota-altering interventions such as probiotics, prebiotics, or fecal microbiota transplantation can synergistically enhance therapeutic effects. For example, co-administration of ginseng polysaccharides with immunotherapy (anti-PD-1) improves antitumor efficacy by reshaping gut microbiota and converting central microbial metabolites. Ginseng fermented food and ginseng dietary fiber are also prebiotics, having further healthy effects on the gut and enhancing the pharmacological effect of ginseng to the maximum (Huang et al., 2021; Zhou et al., 2021; Song et al., 2023). 7.3 Drug interactions and safety assessments Gut microbiota can potentially modify pharmacokinetics and pharmacodynamics of ginseng and thus affect drug interactions and safety. Individual difference in microbiota composition may induce differences in response or side effects. Although ginseng generally is well tolerated, the administration of probiotics or fermentation technology to enhance the bioavailability of ginsenosides needs rigorous safety and efficacy testing. Clinical trials indicate ginseng interventions to be safe in the general population but more work is needed to establish long-term safety, especially with combinations and in people with disrupted microbiota (Zhao et al., 2023; Wu et al., 2024; Zhang et al., 2024).
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