Dietary Lactobacillus johnsonii-derived extracellular vesicles ameliorate acute colitis by regulating gut microbiota and maintaining intestinal barrier homeostasis.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with intricate pathogenesis, and clinical treatment is still not ideal. The imbalance of gut microbiota is associated with IBD progression. Various probiotics have been used as functional foods for the prevention and treatment of IBD, but the specific mechanism is still not fully understood. Lactobacillus johnsonii (L. johnsonii) is a potential anti-inflammatory bacterium, and compared to other probiotic Lactobacillus species, its colonization in the gut of colitis patients is significantly reduced. In this study, we first found that dietary L. johnsonii exerts strong anti-inflammatory and antioxidant effects in colitis mice, and this beneficial effect is directly related to its derived extracellular vesicles (LJ-EVs). Further experimental results indicate that LJ-EVs effectively prevented colitis symptoms and modulated gut microbiota and metabolic pathways. Meanwhile, we have studied for the first time the protective effect of LJ-EVs on the intestinal barrier from the perspective of reducing oxidative stress. We found that LJ-EVs can be directly taken up by intestinal epithelial cells and activate the Nrf2/HO-1 antioxidant signaling pathway, reducing endotoxin damage to cells and maintaining intestinal barrier homeostasis, which cascades to alleviate intestinal inflammation response. This study reveals the mechanism of L. johnsonii in treating colitis and provides a new approach for the development of oral LJ-EVs for the treatment of colitis.