miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease

Modulation of gut microbiota has emerged as a promising therapeutic strategy for inflammatory bowel disease (IBD). However, current interventions such as probiotics and fecal microbiota transplantation remain limited by insufficient safety and efficacy. To address this, we engineered commensal <i>Lactobacillus rhamnosus</i> (LGG) using miRNA-loaded biomimetic nanoparticles to enhance its proliferation and indole-3-carboxaldehyde production. By functionalizing bacterial extracellular vesicles (BEVs) derived from LGG with lipid nanoparticles (LNPs), we developed BEV-LNPs that exhibited enhanced targeting efficiency toward LGG compared to <i>Escherichia coli</i>. In vitro and in vivo studies demonstrated that BEV-LNPs showed superior stability in simulated physiological fluids and gastrointestinal environments compared to conventional LNPs. When combined with 5-aminosalicylic acid, the BEV-LNP formulation notably improved outcomes in acute and chronic colitis models, reducing inflammation, restoring epithelial barrier integrity, and promoting microbial balance. This study presents an effective strategy for colitis treatment by leveraging miRNA-loaded nanoparticles.