Abstract

Edible bird's nest (EBN) and its key component, sialic acid (SA), were investigated for their potential to counteract sepsis‐induced immunosuppression. In a murine “two‐hit” sepsis model, EBN and SA significantly enhanced survival, ameliorated multi‐organ damage, and reduced bacterial dissemination. Crucially, they reversed immunosuppression by restoring the TNF‐α‐secreting capacity of immune cells. Proteomic and KEGG analyses identified T cell proliferation as a central mechanism, which was validated by CFSE assay. Furthermore, we demonstrated that this enhanced T cell proliferation is mediated through the activation of the mTOR signaling pathway. This study reveals that EBN and SA are promising immune‐enhancing agents against sepsis‐induced immunosuppression, offering a novel therapeutic strategy for secondary infections. This study reveals that edible bird's nest (EBN) and sialic acid (SA) efectively reverse sepsis‐induced immunosuppression. EBN and SA enhance T cell proliferation via the activation of the mTOR signaling pathway, and this enhanced proliferation mediates the protective effect. These findings highlight the role of nutritional bioactive compounds in immune regulation and may inform future therapeutic strategies for secondary infections in sepsis.