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

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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 Au 3+ 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, -NH 2 ) 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.

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