Flash nano-encapsulation of probiotics: Bolstering environmental resistance and intestinal colonization to prevent...

Necrotizing enterocolitis (NEC) is one of the most critical gastrointestinal emergency in neonates, characterized by high mortality and frequent long-term complications. Probiotic supplementation provides a targeted approach to modulate the gut microbiota and reduce the risk of NEC. However, the oral delivery of probiotics is significantly compromised by their poor viability and colonization capacity in the hostile gastrointestinal environment, for which nanoencapsulation has evolved as a powerful solution. Current single-cell nanoencapsulation approaches face significant challenges, including complex preparation processes and difficulties in achieving uniform and scalable production. In this study, we pioneered the application of flash nanoencapsulation (FNE) technology to develop a universal nanoencapsulation strategy for diverse probiotic strains. This strategy successfully achieved high-efficiency polyelectrolyte-lipid bilayer single-cell nanoencapsulation of Lactobacillus rhamnosus GG (LGG), thereby significantly enhancing the mucus adhesiveness and oral bioavailability. Moreover, in a neonatal mice model of NEC, encapsulated LGG administration alleviated intestinal inflammation through the TLR4/NF-κB signaling pathway, enhanced intestinal barrier function, and modulated gut microbiota composition, demonstrating promising efficacy and clinical potential in NEC prevention. This work establishes a theoretical foundation for the development of FNE-based probiotic nanoencapsulation technology and the application of encapsulated probiotics in the prevention of NEC.