Ginseng-Douchi ameliorates high-fat diet-induced obesity and metabolic disorders via gut microbiota regulation

Objective This study evaluated the anti-obesity effects of Ginseng-Douchi (SC), a novel functional food fermented from ginseng and soybean (both medicinal and edible resources) using Bacillus subtilis , and explored its gut microbiota regulatory mechanisms in high-fat diet (HFD)-induced obese mice. Methods C57BL/6 mice were fed an HFD to induce obesity and then randomly assigned to normal-control, HFD model, orlistat positive-control, and SC low-, medium-, and high-dose groups. All treatments were administered by gavage for 8 weeks. Body weight, Lee index, serum biochemical indices, and inflammatory cytokines were assessed. Liver, adipose, and colon tissues were harvested for H&E, Oil Red O, and AB-PAS histological staining. For liver and brown adipose tissue, target-gene qPCR, IHC, and protein ELISA were performed. Gut microbiota was profiled by metagenomic sequencing, including taxonomic annotation as well as KEGG and CAZy functional analyses. Results High-dose SC significantly inhibited HFD-induced weight gain (35.74 ± 1.17 g vs. 44.14 ± 1.82 g in HFD), lowered Lee index (345.00 ± 1.19 vs. 375.00 ± 1.86), and reduced visceral fat. Serum TC, TG, and LDL-C were decreased; hepatic steatosis and colonic mucosal barrier damage were alleviated. SC restored UCP1 protein abundance in brown adipose tissue despite reduced Ucp1 transcript levels after intervention, lowered serum TNF-α, IL-6 and LPS, and raised IL-10. Metagenomics showed that SC did not significantly reverse HFD-induced decline in α-diversity, but selectively suppressed HFD-enriched Schaedlerella and Faecalibaculum , while enriching Bifidobacterium . Conclusion The SC is associated with ameliorated HFD-induced obesity and metabolic disorders, accompanied by multiple inter-related biological events including component biotransformation, targeted modulation of specific gut taxa, improved intestinal barrier status, and restored BAT UCP1 protein abundance. These findings provide experimental support for fermented medicinal-food products as potential dietary interventions for obesity.