Mechanism of fermented Astragalus membranaceus regulating chicken EVs to up-3 regulate the expression of interferon and interleukin

Astragalus membranaceus has been found to have a significant regulatory effect on the20 expression of interferon and interleukin, especially after microbial fermentation.21 However, the exact mechanism by which Astragalus membranaceus regulates these22 immune response pathways is still unknown. Recent studies have shown that23 extracellular vesicles (EVs) regulate various immune response pathways through24 bioactive substances mediated by EVs. In this study, it was found that the number of25 EVs in the peripheral blood of chicken fed fermented Astragalus membranaceus was26 significantly altered, and that EVs had a significant promoting effect on the expression27 of IFN-α, IFN-β, and IL-2 in chicken macrophages. The results of differential miRNA28 analysis in EVs showed that miRNA-1388a, which was significantly up-regulated in29 EVs, and an important miRNA that promoted the expression of IFN-α, IFN-β and IL30 2. Comparative analysis of miRNA target genes and mRNA expression profiles in31 peripheral blood of chicken fed FA showed that target genes regulated by miRNA-32 1338a were highly consistent with mRNA expression profiles in peripheral blood of33 chicken. This study shows for the first time that fermented Astragalus membranaceus34 involved in the expression of interferon and interleukin by regulating EVs and their35 mediated miRNA in chicken.