HAMSIAA protects cyclophosphamide induced immunosuppression by modulating gut homeostasis and purine metabolism

Introduction Dietary supplementation with functional starches serves as a promising intervention strategy for immune regulation, yet the immunomodulatory efficacy and underlying mechanisms of newly developed modified starch derivatives remain to be further explored. In this study, a cyclophosphamide (CTX) induced secondary immunodeficiency mouse model was adopted to investigate the immunoregulatory effects of indole 3 acetylated high amylose maize starch derivative (HAMSIAA). Methods Mice were fed a basal diet supplemented with 0.5% or 1% HAMSIAA for nine consecutive days, with CTX administered starting on day 7. Immune organ injury, splenic CD4⁺/CD8⁺ T cell balance, serum immunoglobulins, intestinal barrier integrity, gut microbiota composition and purine related metabolome were assessed. Results HAMSIAA attenuated CTX triggered damage to immune organs, maintained the splenic CD4⁺/CD8⁺ T cell balance, and increased serum levels of Immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). In addition, HAMSIAA improved intestinal barrier integrity and modulated gut microbiota composition, as evidenced by changes in the Bacillota/Bacteroidota (B/B) ratio and a reduction in Pseudomonadota abundance. Metabolomic analyses further revealed that HAMSIAA was associated with modulation of the purine salvage pathway, including downregulation of hypoxanthine guanine phosphoribosyltransferase (HGPRT) and altered levels of metabolites such as inosine and xanthine, which may contribute to its immunoprotective effects. Discussion Collectively, the present findings suggest that HAMSIAA is a promising functional food ingredient for the prophylactic mitigation of chemotherapy induced immunosuppression, and provide support for its translational application in the field of immunonutrition.