Extracellular vesicles from Lactiplantibacillus plantarum: A novel approach to lowering 5-ASA dosage in ulcerative colitis

5-ASA remains the main treatment for UC but faces challenges such as side effects and poor compliance. To address these issues, reducing the dosage and minimizing adverse reactions are pressing priorities. Lactiplantibacillus plantarum, a food-derived probiotic, is recognized for its biological safety. Its extracellular vesicles (LP-EVs), as a new biological agent, have more stable properties than probiotics. Therefore, this study aimed to evaluate whether combination therapy consisting of dose-reduced 5-ASA and LP-EVs could achieve the goal of reducing the 5-ASA dosage without compromising therapeutic efficacy. The combination of LP-EVs and 5-ASA was tested in vivo. The mRNA levels of inflammatory cytokines and tight junction proteins were measured by RT-qPCR. Changes in gut microbiota were analyzed via 16S rRNA sequencing. Results demonstrated that the combined treatment significantly improved colonic tissue barrier function and reduced inflammation in the colitis mouse model, as indicated by improvements in body weight and colon length, along with decreased DAI and histopathology scores. The combination therapy significantly suppressed pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α), while upregulating the anti-inflammatory cytokine IL-10 and tight junction proteins (ZO-1, Occludin, and Claudin-1). This treatment also activated GPR35 and AHR levels. Gut microbiota analysis revealed enrichment of Romboutsia and Muribaculum, suppression of Clostridium, Anaerostipes, and Helicobacter. These findings suggest that the combination of half-dose 5-ASA and LP-EVs is non-inferior to full-dose 5-ASA in alleviating colitis symptoms. This study presents a promising combination therapy for UC using half-dose 5-ASA and LP-EVs, providing a strategy to reduce the required dosage of 5-ASA.