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<p>A novel acidic exopolysaccharide (AEPS) extracted from <i>Cordyceps militaris</i> fermentation broth has potent immunomodulatory activity, but its mechanism with probiotics in immune and gut microbiota regulation remains unclear. This study investigated the prebiotic activity and gastrointestinal digestion resistance of AEPS on <i>Lactiplantibacillus plantarum</i> H8, as well as the immunomodulatory effects of the AEPS-H8 combination on cyclophosphamide (CTX)-induced immunosuppressed mice. Results showed AEPS promoted H8 growth in a dose-dependent manner, protected its activity after in vitro simulated digestion, and enhanced its intestinal release. Supplementation with AEPS, H8, or AEPS+H8 alleviated CTX-induced mice’s weight loss and improved immune organ indices, with the combination showing superior synergy. It also promoted splenic T/B lymphocyte proliferation, elevated cytokines (IL-2, IL-4, IFN-γ) and increased immunoglobulins (IgA, IgM, IgG). 16&#xa0;S rRNA sequencing revealed that AEPS+H8 increased bacterial groups including <i>Muribaculaceae</i> and <i>norank_o_Clostridia_UCG-014</i>, as well as short-chain fatty acids (SCFAs) content, while reducing bacterial groups including <i>Lachnospiraceae</i>, <i>Oscillospiraceae</i>, and <i>Ruminococcaceae</i>. Western blot showed AEPS+H8 promoted the phosphorylation and expression of ERK, JNK and p38, as well as p65, p-IkB-α, Akt, p-Akt, and upstream molecule MyD88. In summary, AEPS+H8 synergistically improves immune parameters, regulates gut microbiota, and mediates MAPK/NF-κB/PI3K-Akt signaling pathways to restore immune responses in CTX-damaged mice, providing evidence for its potential application in functional foods. </p>

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Cordyceps Militaris Exopolysaccharides and Lactiplantibacillus Plantarum H8 Synergistically Improve Immune Function Damage in Cyclophosphamide-Induced Immunosuppressed Mice

  • 期刊论文

  • 发表日期：

    2026年4月24日

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  • Jingjing Xuan,
  • Shengdong Bao,
  • Lidan Guo,
  • Bin Jiang,
  • Ji Wang,
  • Dayong Ren

摘要

A novel acidic exopolysaccharide (AEPS) extracted from Cordyceps militaris fermentation broth has potent immunomodulatory activity, but its mechanism with probiotics in immune and gut microbiota regulation remains unclear. This study investigated the prebiotic activity and gastrointestinal digestion resistance of AEPS on Lactiplantibacillus plantarum H8, as well as the immunomodulatory effects of the AEPS-H8 combination on cyclophosphamide (CTX)-induced immunosuppressed mice. Results showed AEPS promoted H8 growth in a dose-dependent manner, protected its activity after in vitro simulated digestion, and enhanced its intestinal release. Supplementation with AEPS, H8, or AEPS+H8 alleviated CTX-induced mice’s weight loss and improved immune organ indices, with the combination showing superior synergy. It also promoted splenic T/B lymphocyte proliferation, elevated cytokines (IL-2, IL-4, IFN-γ) and increased immunoglobulins (IgA, IgM, IgG). 16 S rRNA sequencing revealed that AEPS+H8 increased bacterial groups including Muribaculaceae and norank_o_Clostridia_UCG-014, as well as short-chain fatty acids (SCFAs) content, while reducing bacterial groups including Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae. Western blot showed AEPS+H8 promoted the phosphorylation and expression of ERK, JNK and p38, as well as p65, p-IkB-α, Akt, p-Akt, and upstream molecule MyD88. In summary, AEPS+H8 synergistically improves immune parameters, regulates gut microbiota, and mediates MAPK/NF-κB/PI3K-Akt signaling pathways to restore immune responses in CTX-damaged mice, providing evidence for its potential application in functional foods.