Aspergillus oryzae Fermentation of Lophatheri Herba Elevates SCFAs and Transforms Flavonoids to Fortify the Gut Barrier via Microbiota Remodeling in Mice.

Background: Lophatheri Herba, a traditional East Asian herb with documented food uses, contains bioactive flavonoids. This study investigated how Aspergillus oryzae fermentation modifies its short-chain fatty acids (SCFAs) and metabolome, and evaluated the fermented product's impact on intestinal barrier function in mice.

Methods: Fermented leaf extracts were analyzed via GC-MS/LC-MS for SCFAs and metabolites. Forty-eight mice were divided into control (standard diet) and three experimental groups (25, 50, 100 mg/kg/day fermented product). After a 4-week intervention, duodenal morphology, colonic cytokines (IL-6/IL-1β), and cecal microbiota were assessed.

Results: We identified significant SCFAs optimization. Significantly increased: acetic acid; butyric acid (p < 0.001); isobutyric acid (p < 0.01); isovaleric acid (p < 0.05). No significant change: propionic acid and isohexanoic acid. Significantly decreased: valeric acid and hexanoic acid (p < 0.001). Metabolomic remodeling showed (i) flavonoid pathway activation and (ii) key metabolite upregulation (daidzein, 4,7-dihydroxyflavone, 3,7-dimethylquercetin, aloe-emodin, soyasapogenol M1, etc.). Gut function peaked at 100 mg/kg with 18% higher duodenal villus height (p < 0.05), improved villus/crypt ratio, and reduced IL-6/IL-1β. Probiotic taxa including Lactobacillus, unclassified f__Lachnospiraceae, Dubosiella, and Monoglobus increased.

Conclusions: Fermented Lophatheri Herba protects gut health through synergistic SCFAs optimization, flavonoid enrichment, and probiotic proliferation, supporting its potential as a microbiota-targeting functional food ingredient.