Nanocoated probiotics by expressing PET hydrolase to efficiently regulate gut dysbiosis induced by nanoplastics

EcN expressed Is PETase for direct nanoPET biodegradation. • Nanocoating enhanced gastrointestinal tolerance and gut retention of probiotics. • EcNp@PDA-PEI effectively reduced nanoPET uptake. • Engineered probiotics reversed barrier disruption and microbiota dysbiosis. Nanoplastics represent emerging environmental contaminants that pose significant threats to human health. Current research on nanoplastics predominantly focuses on their environmental impact and ex situ degradation. A critical paradigm shift is needed toward developing strategies for their in vivo elimination and therapy. Addressing this gap, a living therapeutic agent based on Escherichia coli Nissle 1917 (EcN) is engineered in this study for charge-enhanced adsorption and remediation of polyethylene terephthalate nanoplastics (nanoPET) in the gastrointestinal tract. This engineered probiotic, EcNp@PDA-PEI, is designed to express PET hydrolase for direct nanoPET biodegradation and coated by polydopamine-polyethyleneimine (PDA-PEI) for prolonging gut retention. The EcNp@PDA-PEI effectively reduces nanoPET uptake by Caco-2 cells, thereby alleviating cellular inflammation and gut barrier disruption. In a murine model of nanoPET-induced colitis, the EcNp@PDA-PEI robustly restores gut barrier integrity, mitigates inflammation, and recalibrates the dysregulated gut microbiota. This work presents a proof-of-concept demonstration of repurposing a PET-degradation system from environmental remediation toward preliminary biomedical exploration, providing a foundational basis for further investigations into nanoplastics-associated health risks. Download: Download high-res image (168KB) Download: Download full-size image