Abstract
Sepsis is a life‐threatening condition characterized by severe organ dysfunction resulting from an uncontrolled host response to infection. Sepsis treatment poses a challenge due to its complexity and the need for effective therapeutic approaches. The objective of this study was to evaluate the immunomodulatory and antimicrobial effects of exopolysaccharides (EPS) from
Auricularia auricula
in a murine model of lethal sepsis. Our findings demonstrated that treatment with EPS significantly enhances the proliferation of circulating lymphocytes and granulocytes, which is associated with improved host defense mechanisms. Additionally, EPS administration effectively mitigates sepsis‐induced pulmonary damage, as evidenced by preserved lung function. Furthermore, EPS treatment significantly reduces microbial translocation to the bloodstream, maintaining a lower colony‐forming unit (CFU) count and thereby restricting systemic infection. The polysaccharides also prevent the development of thrombocytopenia in septic animals, thereby preserving platelet homeostasis. The compound modulates serum cytokine profiles, contributing to a more regulated inflammatory response. The interactome analysis reveals that the Dectin‐1 → Syk pathway activates NF‐κB/AP‐1 and involves p38 MAPK, thereby explaining the observed cytokine modulation. The presence of Nod2/Ripk2 suggests that the EPS primes leukocytes to effectively combat both fungi and bacteria, leading to a reduced bacterial load and increased survival. Collectively, these data indicate that EPS, a prebiotic agent, represents a novel therapeutic strategy with potential for modulating immune responses, controlling microbial proliferation, and improving survival outcomes in a model of severe sepsis.