Panax ginseng as a microbial ecosystem modulator: implications for systemic health via the gut-organ axes

Panax ginseng C.A. Meyer, a renowned medicinal herb, exerts many of its systemic effects through intricate interactions with the gut microbiota, a relationship that also addresses the challenge of its own limited oral bioavailability. This review comprehensively examines the role of ginseng and its bioactive constituents in modulating gut microbiota and their subsequent influence on host health through key gut-organ axes. Based on an in-depth analysis of literature, we summarize how ginseng intervention is associated with a modulated gut microbial ecology-characterized by enriched beneficial taxa and suppressed pathogens-and is further linked to enhanced barrier integrity, regulated microbial metabolites, and reduced inflammation and oxidative stress. These mechanisms underlie its protective effects across multiple organ systems, including the gut-brain, gut-liver, gut-lung, gut-heart, and gut-kidney axes, ameliorating conditions such as cognitive decline, hepatic inflammation, pulmonary fibrosis, atherosclerosis, and renal injury. Clinical evidence further associates ginseng with improved metabolic and cognitive parameters correlated to microbial changes. We conclude that the therapeutic activity of ginseng appears to involve, and is likely modulated by, its prebiotic-like influence on the gut microbiota. However, the degree to which its efficacy is microbiota-dependent varies across different organ systems, as established by current evidence. Further mechanistic and clinical studies, particularly those employing causal models, are essential to definitively validate its potential in treating chronic diseases via microbiota-based strategies. • Gut microbiota mediates Panax ginseng ’s multi-organ protective effects. • Panax ginseng modulates the gut-brain, -liver, -heart, -lung, and -kidney axes. • Panax ginseng ’s efficacy involves SCFAs, antiinflammation, and antioxidation regulation. • Clinical translation requires further human trials and mechanistic investigation.