Goat milk derived small extracellular vesicles ameliorate LPS-induced intestinal epithelial barrier dysfunction, oxidative stress, and apoptosis by inhibiting the MAPK signaling pathway.

Abstract

Intestinal injury is often accompanied by epithelial barrier dysfunction, oxidative stress, and apoptosis. Previous research studies have demonstrated that small extracellular vesicles (sEVs) from animal milk play a crucial role in regulating intestinal injury. Nonetheless, there has been limited research on the impact of goat milk sEVs on intestinal damage. This study aims to explore the functional differences between proteins in colostrum-derived sEVs (CME) and mature milk-derived sEVs (MME) from goat and elucidate their effects and mechanisms on lipopolysaccharide (LPS)-induced injury in IEC-6. Proteomic analysis revealed that both CME and MME are rich in various bioactive proteins that have regulatory effects on cell damage. CME and MME significantly improved LPS-induced IEC-6 barrier dysfunction and oxidative stress. Additionally, CME and MME alleviated LPS-induced IEC-6 proliferation inhibition and apoptosis. Notably, CME exhibited a more significant improvement effect. RNA-Seq analysis indicated that CME ameliorates IEC-6 injury by inhibiting multiple genes and signaling pathways associated with cell damage, particularly the MAPK signaling pathway. In summary, goat milk-derived sEVs improve LPS-induced IEC-6 injury by targeting the MAPK signaling pathway, significantly restoring the intestinal epithelial barrier function, reducing oxidative stress, and alleviating apoptosis. These findings offer scientific evidence supporting the potential application of goat milk-derived sEVs as protective agents against intestinal injury.