Anti-diabetic effects of douchi-derived peptide-rich fraction on high-fat-diet and streptozotocin-treated mice and the underlying mechanisms by gut microbial metagenomic and hepatic transcriptomic profiling

In this study, a peptide-rich fraction (DPF) was isolated from Chinese douchi. The chemical compositions and peptide sequences of DPF were characterized. Subsequently, DPF was administered to high-fat diet (HFD)- and streptozotocin (STZ)-treated mice to evaluate its anti-diabetic potential. DPF contained 65.0 % peptide (by dry weight), with 288 peptide sequences identified. Animal experiments demonstrated that DPF significantly mitigated weight loss, decreased damage to the liver and pancreas, reduced glucose levels, improved glucose intolerance, increased insulin levels, and lowered total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels in HFD- and STZ-treated mice compared to diabetic mice, underscoring its anti-diabetic effects. Moreover, DPF partially counteracted the dysbiosis of gut microbiota in mice. Furthermore, hepatic transcriptomic profiling identified 821 differentially expressed genes, corresponding to 291 enriched KEGG pathways. These findings advance the current understanding of the bioactive potential of Chinese douchi and support its applications in functional foods for diabetes management.