Inflammatory bowel disease (IBD) is a chronic intestinal disorder characterized by barrier dysfunction, for which effective treatments are still lacking. Plant-derived extracellular vesicles represent an emerging class of natural nanotherapeutics. In this study, we isolated and characterized extracellular vesicles from barley leaf (BLEVs), demonstrating typical vesicular morphology with an average diameter of 177 nm and negative surface charge. BLEVs exhibited excellent biosafety, stability, and colon-targeting capability upon oral administration. In mouse models of colitis induced by dextran sulfate sodium or Citrobacter rodentium, BLEVs significantly restored intestinal barrier integrity. Using colonic organoids, we further showed that BLEVs promote intestinal stem cell proliferation and epithelial regeneration through activation of the retinoic acid (RA) metabolism pathway. Critically, pharmacological inhibition of retinaldehyde dehydrogenase (RALDH) abolished the protective effects of BLEVs, identifying RALDH as a key molecular target. These findings position BLEVs as a promising therapeutic strategy for IBD, highlighting RA signaling as a potential target for epithelial homeostasis restoration.

Neurodegenerative diseases (NDs), mainly including Alzheimer's disease, Parkinson's disease, and multiple sclerosis, represent a major public health challenge with the steady increase of aging population worldwide. Emerging evidence has revealed the key role of the microbiota-gut-brain axis in the pathogenesis of NDs. Diet is one of the most important environmental factors shaping the structure and function of gut microbiota. Manipulating the gut microbiota through specific diet patterns may represent a promising approach for NDs prevention. In this review, we highlight gut microbiota variations in NDs, outline several crucial signaling pathways of the gut-brain communication, and discuss the interplay of nutrients-microbes and biological effect of diet-derived microbial metabolites on neural physiology. In particular, we summarized the current knowledge about the application of dietary patterns in NDs to prevent disease progression via the modulation of the gut microbiota. Our study provides novel insights on the diet-microbiota-gut-brain axis in neurodegenerative disorders and highlights the potential of developing microbiome-targeted personalized dietary intervention for NDs management.