Comparative metabolomic and microbiome characterization of herbal and traditional Baijiu during in vitro gastrointestinal digestion

BACKGROUND: Herbal Baijiu (HB) and traditional Baijiu (TB) contain complex chemical matrices whose metabolic fate during gastrointestinal digestion and subsequent impact on gut microbiota remain unclear. This study systematically compared HB and TB through in vitro gastrointestinal digestion to evaluate the differences in digestive profiles and microbial communities. RESULTS: Volatile metabolite profiling demonstrated that HB maintained higher stability of ester compounds, particularly ethyl pentanoate, throughout digestion, whereas TB accumulated higher levels of potentially undesirable compounds such as 2,4-di-tert-butylphenol during small intestinal digestion. Moreover, non-volatile metabolites analysis revealed clear separation between HB and TB after gastric and small intestinal digestion, while minimal differences were observed during oral digestion. HB exhibited a greater number of differential metabolites during small intestinal digestion than TB, indicating stronger digestion-induced metabolic remodeling. KEGG enrichment analysis indicated that HB was associated with lipid metabolism, bile acid biosynthesis, and one-carbon metabolism pathways, whereas TB predominantly enriched glutathione metabolism and aromatic amino acid metabolism, reflecting stronger oxidative stress responses. During fermentation, HB promoted a more beneficial and functionally diverse microbial profile, characterized by enrichment of Bifidobacterium and Lactobacillus, as well as dynamic succession of Clostridium (63.81% at 24 h) and Veillonella (54.52% at 72 h). Correlation analysis further linked HB-associated metabolites with beneficial microbial genera, whereas TB was associated with Acidaminococcus and Fusobacterium nucleatum. CONCLUSION: HB and TB exhibited distinct digestion-dependent metabolic and microbial trajectories. HB more effectively modulated digestion-derived metabolites and promoted a more favorable gut microbial profile compared with TB. © 2026 Society of Chemical Industry.