Two protein‐derived peptides from <i>Bombyx mori</i> attenuate colitis by enhancing intestinal barrier function and modulating gut microbiota ecology

Abstract 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.