Bariatric surgery is the most effective treatment for obesity and its comorbidities. However, our understanding of the molecular mechanisms behind its beneficial effects is limited. Extracellular vesicles (EVs) comprise an important mode of intercellular communication. They carry nucleic acids, hormones and signaling molecules, and regulate multiple processes. Our aim was to test the role of EVs in the effects of vertical sleeve gastrectomy (VSG) using a mouse model.Small intestinal EVs were obtained from the mice that underwent VSG or control surgery and were on chow, high-fat diet or diet-restricted, and then subjected to the proteomic analysis. Enteroid and bacterial cultures were treated with EVs to evaluate their survival effect. A mouse cohort received intraduodenal administration of EVs from VSG or Sham mice for 10 days. Body weight, glucose metabolism and intestinal morphology were evaluated. EVs were enriched in the intestinal lumen and mucus of VSG compared to Sham mice. Protein composition of VSG and Sham-derived EVs was highly distinct. When introduced into culture, VSG EVs decreased survival of intestinal enteroids, and conversely, promoted proliferation of bacteria. Mice administered with EVs obtained from VSG and Sham groups did not show difference in body weight, food intake and glucose metabolism. Intestinal morphology was altered as VSG EVs caused reduction of ileal villi length and decreased epithelial proliferation in the jejunum and ileum. VSG causes remodeling of intestinal EVs which results in unique protein composition. VSG-derived EVs exhibit cytotoxic effect on epithelial cells and reduce proliferation of intestinal progenitor cells in mice.

中文翻译：

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垂直袖状胃切除术改变肠细胞外囊泡

减肥手术是治疗肥胖症及其合并症最有效的方法。然而，我们对其有益作用背后的分子机制的理解是有限的。细胞外囊泡 (EVs) 是细胞间通讯的重要模式。它们携带核酸、激素和信号分子，并调节多个过程。我们的目的是使用小鼠模型测试 EV 在垂直袖状胃切除术 (VSG) 效果中的作用。小肠 EV 是从接受 VSG 或对照手术的小鼠身上获得的，并且是食物、高脂饮食或节食-限制，然后进行蛋白质组学分析。用 EV 处理肠和细菌培养物以评估它们的生存效果。一组小鼠接受来自 VSG 或 Sham 小鼠的 EV 十二指肠内给药 10 天。体重，评估葡萄糖代谢和肠道形态。与 Sham 小鼠相比，EVs 在 VSG 的肠腔和粘液中富集。VSG 和 Sham 衍生的 EV 的蛋白质组成高度不同。当被引入培养物中时，VSG EVs 会降低肠道小肠的存活率，相反，会促进细菌的增殖。给予从 VSG 和 Sham 组获得的 EV 的小鼠在体重、食物摄入和葡萄糖代谢方面没有表现出差异。随着 VSG EV 导致回肠绒毛长度减少和空肠和回肠上皮增殖减少，肠道形态发生改变。VSG 导致肠道 EV 的重塑，从而导致独特的蛋白质组成。VSG 衍生的 EV 对上皮细胞具有细胞毒性作用，并减少小鼠肠道祖细胞的增殖。