Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem 9112001, Israel.
Nutrition and Dietetic Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel.
Nutrients. 2020 Aug 26;12(9):2589. doi: 10.3390/nu12092589.
The aim of this study was to investigate the therapeutic effect of cow and human milk derived exosomes (MDEs) on colitis. We used gavage administration of fluorescent labeled MDEs to track their localization patterns in vivo and studied their therapeutic effect on colitis in a dextran sulfate sodium (DSS)-induced colitis model. MDEs attenuated the severity of colitis induced by DSS and statistically reduced the histopathological scoring grade and shortening of the colon. Likewise, treatment with MDEs reduced the expression of interleukin 6 and tumor necrosis factor-α. Moreover, miRNAs highly expressed in milk, such as miRNA-320, 375, and Let-7, were found to be more abundant in the colon of MDE-treated mice compared with untreated mice; contrastingly, the expression of their target genes, mainly DNA methyltransferase 1 (DNMT1) and DNMT3 were downregulated. Furthermore, the level of TGF-β was upregulated in the colon of MDE-treated mice. We demonstrated that MDEs have a therapeutic and anti-inflammatory effect on colitis, involving several complementary pathways in its mechanism of action. The therapeutic effects of MDEs might have implications for the possible addition of MDEs as a nutrient in enteral nutrition formulas for patients with inflammatory bowel disease.
本研究旨在探讨牛源和人源乳衍生外泌体（MDEs）对结肠炎的治疗作用。我们通过灌胃给予荧光标记的 MDEs，来追踪其在体内的定位模式，并在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中研究其对结肠炎的治疗作用。MDEs 减轻了 DSS 诱导的结肠炎的严重程度，并在统计学上降低了组织病理学评分等级和结肠缩短。同样，MDEs 治疗降低了白细胞介素 6 和肿瘤坏死因子-α的表达。此外，在 MDE 处理的小鼠结肠中发现了高度表达于乳汁中的 miRNAs，如 miRNA-320、375 和 Let-7，其表达水平明显高于未处理的小鼠；相反，其靶基因主要为 DNA 甲基转移酶 1（DNMT1）和 DNMT3 的表达下调。此外，MDE 处理的小鼠结肠中 TGF-β水平上调。我们证明 MDEs 对结肠炎具有治疗和抗炎作用，其作用机制涉及多个互补途径。MDEs 的治疗效果可能意味着在炎症性肠病患者的肠内营养配方中添加 MDEs 作为营养物质具有一定的意义。
