Triple-Functional Probiotics with Intracellularly Synthesized Selenium Nanoparticles for Colitis Therapy by...

Area of Science:

• Biomedical Engineering
• Microbiology
• Immunology

Background:

• Colitis pathogenesis involves dysregulated macrophage phenotypes, oxidative stress, and gut microbial dysbiosis.
• Current colitis treatments struggle to address these interconnected issues simultaneously.
• A multi-targeted therapeutic approach is crucial for effective colitis management.

Purpose of the Study:

• To develop a novel probiotic, Se@EcN-C2/A2, capable of simultaneously addressing oxidative stress, inflammation, and gut dysbiosis in colitis.
• To evaluate the therapeutic and prophylactic efficacy of Se@EcN-C2/A2 in a mouse model of colitis.
• To investigate the underlying mechanisms of Se@EcN-C2/A2 in regulating macrophage polarization and gut microbiota.

Main Methods:

• Engineered *Escherichia coli* Nissle 1917 (EcN) to synthesize selenium nanoparticles (Se@EcN).
• Coated Se@EcN with glycol chitosan and sodium alginate to create Se@EcN-C2/A2 for enhanced gastrointestinal stability and targeted delivery.
• Administered Se@EcN-C2/A2 to DSS-induced colitis mice and assessed therapeutic effects on oxidative stress, inflammation, macrophage polarization, gut barrier function, and microbial composition.

Main Results:

• Se@EcN-C2/A2 effectively scavenged reactive oxygen species and suppressed inflammatory signaling pathways (TLR and NF-κB).
• The probiotic polarized M1 macrophages to M2 phenotypes via PI3K/AKT activation, reducing inflammation.
• Se@EcN-C2/A2 demonstrated significant therapeutic and prophylactic effects in colitis mice, restoring gut barrier integrity and modulating gut microbiota by reducing *Escherichia-Shigella* and increasing *Lactobacillus* and *Bifidobacterium*.

Conclusions:

• Se@EcN-C2/A2 represents a promising "three-birds-one-stone" therapeutic strategy for colitis.
• The engineered probiotic effectively mitigates key pathological features of colitis, including oxidative stress, inflammation, and gut dysbiosis.
• This multi-targeted probiotic approach holds potential for future clinical applications in inflammatory bowel disease treatment.