Two protein-derived peptides from Bombyx mori attenuate colitis by enhancing intestinal barrier function and modulating gut microbiota ecology

Food-sourced proteins have been shown to have ameliorative effects on ulcerative colitis (UC), and studies have identified potential anti-inflammatory activity of silkworm pupa proteins. Here, we identified and screened two novel protein-derived peptides, PDLGLF (PD-6) and GTEGGFPF (GT-8), from Bombyx mori using UPLC–MS/MS and bioinformatics analysis. These peptides can serve as effective experimental drugs for colitis by modulating the gut microbiota. Treatment with peptides PD-6 and GT-8 inhibited colitis inflammation in UC mice, improved oxidative stress levels, and maintained intestinal epithelial barrier function. Peptides PD-6 and GT-8 also altered the diversity and composition of the gut microbiota in UC mice and increased the concentration of short-chain fatty acids. In conclusion, these findings reveal the potential of the naturally derived bioactive peptides PD-6 and GT-8 in controlling intestinal inflammation and underscore the potential of PD-6 and GT-8 as promising candidates for the prevention and improvement of UC-related inflammatory diseases.