Peptide combination therapy reshapes intestinal microenvironment for colitis treatment

Mouse colonic organoid transplantation has been reported as a novel therapy for colitis. In this study, we identified a cell-penetrating peptide that targets RIPK1 to alleviate necroptosis, which significantly enhanced the therapeutic efficacy of organoid transplantation. Single-cell RNA sequencing (scRNA-seq) analysis was performed on colon tissues from mice that received transplantation alone or transplantation followed by peptide administration. The results demonstrated that the combination therapy reshaped the intestinal microenvironment by increasing the numbers of epithelial and stem cells and reprogramming cell communication between epithelial and stromal compartments, thereby improving the regenerative capacity of the colon tissue.