Holothuria leucospilota Polysaccharides Improve Immunity and the Gut Microbiota in Cyclophosphamide‐Treated Immunosuppressed Mice

Immunosuppression is one of the major risk factors for a series of diseases, such as tumor, rheumatoid arthritis, and microbial infection. Various natural products have attracted wide attention due to their immunomodulatory activities. Herein, the study investigates the regulation of Holothuria leucospilota polysaccharides (HLP) in immunosuppressed mice.Eight-week-old female BALB/c mice are injected intraperitoneally with cyclophosphamide (80 mg kg-1 body weight day-1 ) to establish the immunosuppressive model. After 12 days of HLP treatment, the immune organ indexes, serum cytokines, and immunoglobulin levels are significantly increased in immunosuppressed mice (p < 0.05). Real-time fluorescent quantitative polymerase chain reaction and western blotting analysis find that HLP improves the immune factors, T-cell markers, and Toll-like receptors (TLR) pathway-related proteins expression. Simultaneously, HLP significantly increases the short-chain fatty acids concentration and regulates the gut microbiota composition (p < 0.05). Furthermore, the metagenomics analysis shows that HLP increases the levels of functional genes involved in amino acid metabolism, carbohydrate metabolism, and growth activity of the gut microbiota.HLP intervention improves the mice's immune function, and the beneficial effects are closely associated with intestinal homeostasis regulation and TLR pathway activation. This study suggests the potential for HLP as prebiotics in novel immunopotentiators development.