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Goat milk exosomal microRNAs alleviate LPS-induced intestinal inflammation in mice. International journal of biological macromolecules Intestinal inflammation is a common digestive system disease. Milk-derived exosomes can participate in intercellular communication and transport a variety of bioactive components, and the microRNAs (miRNAs) they carry play important roles in a variety of biological processes in the body. At present, the preventive effect and mechanism of action of goat milk exosomes and their derived miRNAs on intestinal inflammation are still unclear. In this study, the protective effect of goat milk exosomes on LPS-induced intestinal inflammation was investigated using mouse intestinal inflammation model and IEC-6 cell inflammation model. Small RNA sequencing was used to analyze the miRNA expression profile of goat milk exosomes. In this study, C-Exo and M-Exo alleviated intestinal inflammation by reducing the LPS-induced release of proinflammatory cytokines, inhibiting the increase in the NLRP3 protein and the activation of the TLR4/NFκB signaling pathway. C-Exo has a more significant inhibitory effect on them, and better therapeutic efficacy than M-Exo. Notably, the target genes of miRNAs in C-Exo and M-Exo were significantly enriched in immune-related pathways. Furthermore, their derived miR-26a-5p and miR-30a-5p were found to ameliorate the IEC-6 inflammatory response. These findings suggest that miRNAs in goat milk exosomes have the potential to attenuate LPS-induced intestinal inflammation. 10.1016/j.ijbiomac.2024.131698