Polysaccharide SP-3 derived from Saposhnikovia divaricata (Turcz.) Schischk. enhances immunity by regulating intestinal targets and gut microbiota.

BACKGROUND

Saposhnikovia divaricata (Turcz.) Schischk. plays a significant role in immune regulation; however, studies on the immune regulatory activities of its constituent polysaccharides, especially homogeneous polysaccharides, are limited.

PURPOSE: This study aimed to investigate the immunomodulatory effects and mechanisms of a homogeneous S. divaricata polysaccharide, SP-3.

METHODS

Based on a preliminary exploration of the immunomodulatory activity of SP-3 in the Pseudomonas aeruginosa PA14-infected Caenorhabditis elegans, a mouse model of immunosuppression was constructed using cyclophosphamide (CTX) and the immunostimulatory effects and underlying mechanisms of SP-3 were investigated from the perspectives of intestinal mucosal immunity and the gut microbiota.

RESULTS

SP-3 significantly extended lifespan, enhanced vitality, increased body fat content, and improved the reproductive capacity of P. aeruginosa PA14-infected C. elegans, which indicated that SP-3 can boost innate immunity. In the CTX-induced immunosuppressed mice, SP-3 protected the immune organs (spleen and liver), restored hematological parameters, including red blood cell and platelet counts, and enhanced systemic immunity. Mechanistically, SP-3 activated the homing pathway of immunoglobulin A (IgA)+ plasma cells to promote IgA secretion in the small intestine and stimulated the TLR-NF-κB signaling pathway to enhance cytokine secretion by CD4+ T cells, thereby strengthening intestinal mucosal immunity. Additionally, analysis of the gut microbiota revealed that SP-3 improved microbial diversity, reduced the abundance of harmful bacteria (Prevotellaceae, Alloprevotella, Rikenellaceae RC9 gut group), and increased the abundance of beneficial bacteria (Bacteroidaceae, Muribaculaceae, Lachnospiraceae, Lactobacillaceae, Ligilactobacillus), effectively restoring CTX-induced intestinal dysbiosis.

CONCLUSION

SP-3 acts as an immune enhancer to protect intestinal mucosal immunity by regulating intestinal targets and gut microbiota, thereby enhancing overall immunity.