Oral administration of probiotic spores-based biohybrid system for efficient attenuation of Salmonella Typhimurium-induced colitis

Salmonella Typhimurium (S. Tm), a Gram-negative pathogenic bacterium, is one of the most common causes of invasive bacterial diseases. Antibiotic therapy remains the principal therapeutic modality for treating S. Tm infection. However, due to the difficulty in precisely targeted pathogenic bacteria after oral administration, the therapeutic effect remains unsatisfactory. Here, we developed an oral probiotic spores-based biohybrid delivery system (BCs@PME-Au) to treat S. Tm-induced colitis. By employing a one-pot metal deposition method, Polymyxin E (PME) acted as a reducing agent to promote the Au³⁺ rapid nucleation and growth into PME-capped Au NPs (PME-Au NPs). By forming Au-S and Au-N bonds with the active sites (-SH, -NH₂) of Bacillus coagulans spores (BCs), PME-Au NPs were anchored onto the surface of BCs to construct the biohybrid system BCs@PME-Au. Following oral administration, BCs@PME-Au successfully passed through the gastric acid barrier. After absorbed water and nutrients, BCs germinated into Bacillus coagulans (BC) in the gut and PME-Au NPs were released. Based on the BC's targeting pathogen infection site and PME-Au NPs' targeting Gram-negative bacteria, the biohybrid system achieved significantly antibacterial effect of S. Tm. Mechanistically, by blocked the LPS-induced inflammatory pathway TLR4/MyD88/NF-κB, BCs@PME-Au exerted a powerful anti-inflammatory effect. With its robust antibacterial efficacy, targeted delivery, and excellent safety profile demonstrated both in vitro and in vivo, the biohybrid system BCs@PME-Au offers significant promise in treating bacterial colitis.