Engineered Probiotics Mitigate Gut Barrier Dysfunction Induced by Nanoplastics

Micro- and nanoplastics, particularly those derived from food-contact materials like polyethylene terephthalate (PET), can damage gut barriers, making the gastrointestinal system more vulnerable to inflammation and infections. Here, a probiotic-based drug delivery system (EcN_T@L) is devised to mitigate nanoplastics-induced gut barrier dysfunction by modulating gut immunity and microbiota. Escherichia coli Nissle 1917 (EcN) is genetically engineered to produce transforming growth factor-β (TGF-β) and then modified with an Eudragit L100-55 coating. This engineered probiotic acts as an in vivo "drug factory", exerting anti-inflammatory and immune-regulatory effects, with improved retention and bioavailability in the gastrointestinal tract. EcN_T@L effectively protects Caco-2 cells from inflammation and infections induced by nano PET, primarily by activating the NF-κB signaling pathway. Besides, EcN_T@L demonstrates superior in vivo therapeutic efficacy in treating gastrointestinal infection caused by the combined presence of nano PET and Salmonella, outperforming commercial antibiotics due to its ability to modulate immune responses and gut microbiota. This study highlights the potential of probiotic-based drug delivery systems in addressing nanoplastics-induced gut dysfunctions, offering a promising strategy for mitigating the environmental impact of micro- and nanoplastics.