Protective effects of human breast milk-derived exosomes on inflammatory bowel disease through modulation of immune cells

Human breast milk (HBM)-derived exosomes play a crucial role not only in infant nutrition but also in modulating inflammation, immunity, and epithelial cell protection. This study investigated how HBM-derived exosomes regulate immune cell development and function. The exosomes promoted the differentiation of naïve CD4⁺ T cells into Treg and Th2 cells while suppressing their differentiation into Th17 and Th1 cells. They also enhanced the proliferation of intestinal epithelial Caco-2 cells and reduced apoptosis in dextran sulfate sodium (DSS)-damaged caco-2 cells. In a DSS-induced colitis mouse model, the exosomes significantly alleviated disease severity, as evidenced by improvements in colon length, disease activity index, and histology grades. Furthermore, the exosomes normalized CD4⁺ T cell subsets in the spleen, mesenteric lymph nodes, and colon, restoring levels comparable to controls. These findings suggest that HBM-derived exosomes hold promise as a potential therapeutic strategy for inflammatory bowel disease by modulating T-cell responses and protecting intestinal epithelial cells.