Red Ginseng Extract Intake and Changes in Metabolite Profiles, Gut Microbiota, and Immune Responses of Healthy Rats

Background: Red ginseng (RG) exhibits enhanced bioactivity compared to white ginseng. Although the beneficial effects of RG have been well investigated in disease models, its impacts on the metabolome, gut microbiota, and immune response under normal physiological conditions remain poorly understood. Methods: Rats were randomized into three groups: control (normal diet), RL (low-dose RGE at 100 mg/kg body weight), and RH (high-dose RGE at 200 mg/kg body weight). After five weeks, metabolite profiles of the blood, liver, kidney, and large intestinal contents were analyzed and the gut microbiota was assessed. Splenocytes were isolated and treated with or without ethanol-precipitated carbohydrate fractions isolated from RGE or from intestinal contents, and IL-12 secretion was measured. Additionally, the correlations among biochemical characteristics, metabolites, gut microbiota, and immune markers were analyzed. Results: RGE intake decreased plasma triglycerides, liver function biomarkers, and epididymal adipose tissue weight. It also altered metabolite profiles for plasma, liver, kidney, and intestinal contents and increased the hepatic NAD⁺/NADH ratio. RGE intake reduced the populations of harmful bacteria, whereas it increased Lachnospiraceae. RGE intake enhanced IL-12 production in splenocytes. Furthermore, splenocytes treated with carbohydrates isolated from the small and large intestinal contents of RGE-fed rats secreted higher IL-12 levels than those of the control group. Conclusions: RGE modulated the gut microbiota, metabolism, and immune responses in healthy rats under normal physiological conditions, warranting further investigation into the underlying mechanisms.