A probiotic BL53 enhances the immunomodulatory and neurorestorative activities of red ginseng in cyclophosphamide-exposed mice through the transformation of ginsenosides to compound K

AIMS: Gut microbiota converts ginsenosides of orally administered red ginseng (RG) into bioactive metabolites such as compound K (CK), with marked interindividual variation. These metabolites exert stronger biological effects than parent ginsenosides. Therefore, we screened probiotic bacteria capable of converting RG ginsenosides to CK and evaluated whether they could enhance the effects of RG on immunosuppression, depression, and cognitive impairment in mice. METHODS AND RESULTS: Bifidobacterium animalis subsp. lactis PB5 and Lactobacillus gasseri PL3, isolated from a human gut microbiota collection, exhibited the strongest ability to convert RG ginsenosides into CK and to increase immune-modulatory and BDNF expression-inducing activity. A (1:4) mixture of PB5 and PL3 (BL53) reduced lipopolysaccharide-induced TNF-α IL-10-1 ratio in macrophages (by 47.8%, P < 0.05) and restored lipopolysaccharide-suppressed BDNF expression in SH-SY5Y cells (by 45.2%, P < 0.05) compared with either PB5 or PL3 alone. Co-administration of BL53 and RG (BRc) enhanced immune responses in cyclophosphamide-exposed mice, compared with either treatment alone, increasing TNF-α, IL-10, and IL-17 levels by 27.0%-96.6% (P < 0.05) and reducing the TNF-α IL-10-1 ratio by 19.5%-27.5% (P < 0.05). BRc also improved cognitive impairment (37.8%) and depression-like behaviors (26.0%-132.0%) and restored hippocampal BDNF (26.9%) (P < 0.05). Plasma CK levels were highest in BRc-treated mice (7.9-fold vs RG, P < 0.05). CONCLUSIONS: BRc significantly alleviates immunosuppression and depression- and cognitive impairment-related symptoms in vivo, which may be attributed to the BL53-mediated enhancement of RG efficacy through PB5-driven biotransformation of RG ginsenosides into CK and PL3-mediated immune modulation and BDNF upregulation.