Food‐Derived Biohybrid Probiotic Extracellular Vesicles for Synergistic Therapy of Inflammatory Bowel Disease

ABSTRACT Inflammatory bowel disease is a chronic gastrointestinal disorder characterized by persistent intestinal inflammation, microbiota dysbiosis, and impaired mucosal barrier function. Conventional treatments, including pharmacological agents, biologics, and fecal microbiota transplantation, are limited by adverse effects, immune suppression, recurrence, and low patient acceptance. In this study, food‐derived probiotic extracellular vesicles (EVs) from Lactiplantibacillus plantarum with dietary polysaccharide (chitosan) and polyphenol (tannic acid) are developed as a synergistic therapeutic strategy for inflammatory bowel disease. The engineered biohybrid with dual‐functional coating confers gastrointestinal stability and colon‐targeted delivery, while scavenging reactive oxygen species and preserving the intrinsic microbiota‐regulating properties of probiotic EVs. Multi‐omics approach reveals correlations among microbial community shifts, short‐chain fatty acids, oxidative stress modulation, inflammatory cytokine profiles, and disease severity indices. This work provides a promising approach and reveals the synergistic mechanisms of engineered probiotic EVs in reshaping gut microbiota, modulating metabolic networks, and improving the inflammatory microenvironment for the treatment of inflammatory bowel disease.