This study aimed to investigate the immune regulation effect of edible bird’s nest (EBN) in vivo and elucidate the influence of EBN on immune microbiome, which is the basis of the activity of EBN. The immunosuppression mice model was established by subcutaneous injection of hydrocortisone (HC). The optimal modeling dose of HC was screened by various immune indexes. Studies have found that the mice immunosuppression model can be constructed with a HC dose of 12.5?mg/kg. The effects of EBN in low (0.285?g/kg) and high doses (0.649?g/kg) were investigated on the immunosuppression mice model. EBN low-dose treatment significantly improved macrophage phagocytosis and NK cell activity in immunosuppression mice. EBN high-dose treatment significantly increased the serum TNF-α content phagocytosis ability of macrophages, NK cell activity and serum hemolysin content of immunosuppression mice. It was found that changes in the intestinal flora are usually accompanied by changes in immune cells and inflammatory factors, so it was hypothesized that there is a correlation between changes in intestinal flora and immune regulation, therefore the changes in the intestinal flora of mice were then investigated after EBN administration. The regulation of intestinal flora experiments showed that species richness decreased in the immunosuppression mice, and after EBN treatment the species richness in mice increased. Additionally, after continuous administration of EBN, the abundance of Bacteroides, Akkermansiaceae and other intestinal probiotics increased, while the abundance of Firmicutes decreased, indicating that EBN can regulate intestinal dysfunction, up-regulate beneficial bacteria. It is reported that the increase of Bacteroides and Akkermansiaceae and the decrease of Firmicutes in the intestinal flora caused an increase in the levels of TNF-α and improved immunity, which is consistent with our experimental results. Therefore, it is hypothesized that EBN plays an immune regulation role mainly by affecting the changes in the intestinal flora. The study provides a theoretical basis for the functional investigation of EBN.
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