Probiotic-based therapy for ulcerative colitis (UC) is a novel and promising approach that has gained much popularity in recent years. However, probiotics may be easily captured and destroyed by the harsh <i>in vivo</i> environment, which limits their application prospects to a large extent. This work introduces a versatile facile approach for decorating individual probiotics with nanozyme coatings, named Pt-Lipid@EcN. A bimolecular lipid coating is deposited on the surface of probiotics used in the oral treatment of UC using simple self-assembly with a liposome under cytocompatible conditions, and it acts as armor to effectively protect the probiotics from strong digestive acids and enzymes. The obtained results indicated that the liposome-coated <i>Escherichia coli</i> Nissle (EcN) 1917 could significantly improve the colonization rate of the microorganisms in the intestinal tract. We also explored the specific mechanism of Pt-Lipid@EcN to improve the behavior of murine UC models, including reduction of inflammatory effects and histological injury, and regulation of epithelial barrier homeostasis in the intestine. The nanozyme-shielded probiotic exhibited enhanced anti-inflammatory ability <i>in vivo</i>, introducing novel strategies for the application of nanozyme biomedicine in the treatment of colonic inflammatory diseases.
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