Abstract: In order to investigate the immunomodulatory effects of short-term administration of Cordyceps militaris on mice in different states and explore its application value as an immunomodulator, Kunming (KM) mice were randomly divided into a low-dose group (DB), a high-dose group (GB) and a control check group (CK). The mice in the DB and GB groups were continuously gavaged with different doses ofan aqueous suspension of C. militaris powder for 21 days, while the CK group was given the same dose of distilled water. Changes in body mass, organ indexes, serum immunoglobulin G (IgG), IgM, interleukin (IL)-2 and IL-10 levels, the percentages of CD3+CD4+ and CD3+CD8+ T lymphocyte subsets in peripheral blood, intestinal flora composition and Toll-like receptor (TLR)2, TLR4, myeloid differentiation factor (MyD) 88 and nuclear factor (NF)-κB expression in the jejunum were measured. Immunosuppressed mice induced by intraperitoneal injection of 80 mg/kg mb cyclophosphamide solution were intragastrically administered with C. militaris for 21 consecutive days. Immune indexes were detected after 0, 7, 14 and 21 days of administration. The results showed that administration of C. militaris at each dose did not cause significant changes in body mass, organ indexes, serum IgG, IgM, IL-2 and IL-10 levels or the percentages of CD3+CD4+ and CD3+CD8+ T lymphocyte subsets in the peripheral blood of mice (P > 0.05). C. militaris could up-regulate the Shannon index and the number of operational taxonomic units (OTU) in the intestinal flora of mice, and increase the diversity and richness of the intestinal flora. The relative abundances of the probiotics Lactobacillus and Alistipes were significantly increased (P < 0.05). The relative abundances of the inflammation-promoting bacteria Clostridium XIVa, Helicobacter and Lachnospiracea_incertae_sedis were significantly decreased (P < 0.05). The expression of TLR4 in jejunum tissues of mice was significantly decreased by all doses of C. militaris (P < 0.05), and the reduction of NF-κB expression was positively correlated with the dose of C. militaris. C. militaris significantly restored organ damage caused by cyclophosphamide in advance, increased the serum levels of IgM, IgG and IL-2 (P < 0.05), and promoted the proliferation of CD3+CD4+ and CD3+CD8+ T lymphocyte subsets in the peripheral blood of immunosuppressed mice. These results showed that short-term administration of C. militaris could reduce the risk of intestinal inflammation without causing an imbalance in the normal immune status. In conclusion, C. militaris can promote recovery from immunosuppression by enhancing humoral and cellular immunity and thus be developed and utilized as an immunomodulator.

Key words: Cordyceps militaris; immune regulation; intestinal flora; immunosuppression