Competitive Inhibition of LPS Binding to CD14 by Bifidobacterium adolescentis FXJWS49M31 Polysaccharide Alleviates TNF-α Secretion and Inflammatory Responses

Bifidobacterium adolescentis, a commensal probiotic, modulates immune responses and inversely correlates with TNF-α production. This study investigates the immunomodulatory effects of the probiotic B. adolescentis FXJWS49M31 and its cell surface polysaccharide (CSP) on lipopolysaccharide (LPS)-induced inflammation. In vitro coculture and in vivo LPS-induced mouse models demonstrated that FXJWS49M31 and its CSP significantly suppressed the secretion of TNF-α and other pro-inflammatory cytokines, alleviating inflammation in the colon and liver. Mechanistic analysis revealed that CSP competitively binds to CD14, blocking the LPS–CD14 interaction and inhibiting activation of the TLR4–NF-κB signaling pathway. Structural modeling identified specific binding sites between CSP1 and CD14, elucidating the molecular basis of its immunoregulatory function. These findings provide a theoretical foundation for the anti-inflammatory properties of probiotic polysaccharides and their potential therapeutic applications.