Integrated multi-omics maps how processed black ginseng modulates gut homeostasis through rare ginsenosides.

Black ginseng, a functional food, is known for enhanced bioactivity, yet systems-level understanding of how its specific bioactive compounds modulate host physiology remains to be elucidated. This study employed an integrated multi-omics approach to map the systemic host responses by which processed black ginseng influences gut health. Through bioactivity-guided screening in a dextran sulfate sodium (DSS)-induced zebrafish model, nine-time steamed black ginseng extract (BG-9) exhibited optimal efficacy in inhibiting neutrophil infiltration and oxidative stress. Chemical profiling by HPLC revealed that rare ginsenosides Rk1, Rg3, and Rg5 were the predominant components in BG-9, collectively accounting for 56.87% of the total ginsenosides. Among them, Rk1 showed the most potent protective effects in vivo. Integrated transcriptomic and metabolomic analyses uncovered that Rk1 intervention significantly reversed DSS-induced metabolic disturbances, primarily by regulating glycine, serine, threonine, and cysteine-methionine metabolism pathways, alongside neuroactive ligand-receptor interactions. These findings provide a multi-omics map delineating that rare ginsenoside Rk1 serves as the primary bioactive constituent through which black ginseng induces systemic physiological changes that modulate gut homeostasis. This work bridges the gap between the consumption of black ginseng as a functional food and its health benefits, offering a systems biology perspective for its application in gut health promotion.