P044 Milk derived exosomes has a therapeutic effect on experimental colitis

Abstract

Background and aims: Inflammatory bowel disease (IBD) is a complex disorder that results from a dysregulated immune response in the gut. Emerging therapy for IBD treatment is mainly focused on the regulation of the immune response. Exosomes are nanovesicle packing different molecules such as miRNAs that transfer their cargo to recipient cells. We and others found that mammalian milk contain a high concentration of exosomes (milk-derived exosomes-MDE) carrying beneficial miRNAs such as miRNA-148. Further, MDE are taken up by different cell type such as intestinal epithelial cells, modify target gene expression, promote proliferation and differentiation of colon epithelial cells. The aim of this study to explore the therapeutic effect of MDE on colitis. Methods: We used gavage administration of MDE labeled with DiR dye to track their localization patterns in vivo. The therapeutic effect of MDE on colitis was studied in mice model of SDS induced colitis, colon length, histopathological scoring grade, cytokine expression, stool consistency, and miRNA expression were analyzed. Results: Imaging of mice that have receive labeled MDE revealed an accumulation of fluorescent signal in the intestine. Moreover, the fluorescent signal in the intestine and liver is time-dependent. MDE reduced the histopathological scoring grade from 5.83±1.47 to 0.6±0.6, p0.05. The length of the colon of MDE treated animals was 7.9±0.19 in comparison to 6.92±0.3 p0.05 of the untreated. The weight loss as a result of the colitis was reverted in MDE treated mice. Likewise, MDE treatment reduced IL-6, TNF-alpha and caveolin expression from 3.83 to 0.78, 1.59 to 0.86 and 3.52 to 1.1 respectively. Highly expressed miRNAs (miRNA-320, 375, Let-7a, and 6073) were found to be more abundant in the colon of MDE treatment mice compared to the untreated. Conclusion: This study demonstrated that MDE have a therapeutic effect on colitis in vivo. Proving the effect of MDE on colitis will have implications for the potential of adding MDE as a therapeutic nutrient to be included in the formulas for IBD patients.